gender reassignment data

Putting numbers on the rise in children seeking gender care

By ROBIN RESPAUT and CHAD TERHUNE

Filed Oct. 6, 2022, 11 a.m. GMT

Thousands of children in the United States now openly identify as a gender different from the one they were assigned at birth, their numbers surging amid growing recognition of transgender identity and rights even as they face persistent prejudice and discrimination.

As the number of transgender children has grown, so has their access to gender-affirming care, much of it provided at scores of clinics at major hospitals.

Reliable counts of adolescents receiving gender-affirming treatment have long been guesswork – until now. Reuters worked with health technology company Komodo Health Inc to identify how many youths have sought and received care. The data show that more and more families across the country are grappling with profound questions about what type of care to pursue for their children, placing them at the center of a vitriolic national political debate over what it means to protect youth who identify as transgender.

Diagnoses of youths with gender dysphoria surge

In 2021, about 42,000 children and teens across the United States received a diagnosis of gender dysphoria, nearly triple the number in 2017, according to data Komodo compiled for Reuters. Gender dysphoria is defined as the distress caused by a discrepancy between a person’s gender identity and the one assigned to them at birth.

Overall, the analysis found that at least 121,882 children ages 6 to 17 were diagnosed with gender dysphoria from 2017 through 2021. Reuters found similar trends when it requested state-level data on diagnoses among children covered by Medicaid, the public insurance program for lower-income families.

Gender-affirming care for youths takes several forms, from social recognition of a preferred name and pronouns to medical interventions such as hormone therapy and, sometimes, surgery. A small but increasing number of U.S. children diagnosed with gender dysphoria are choosing medical interventions to express their identity and help alleviate their distress.

These medical treatments don’t begin until the onset of puberty, typically around age 10 or 11.

For children at this age and stage of development, puberty-blocking medications are an option. These drugs, known as GnRH agonists, suppress the release of the sex hormones testosterone and estrogen. The U.S. Food and Drug Administration has approved the drugs to treat prostate cancer, endometriosis and central precocious puberty, but not gender dysphoria. Their off-label use in gender-affirming care, while legal, lacks the support of clinical trials to establish their safety for such treatment.

Over the last five years, there were at least 4,780 adolescents who started on puberty blockers and had a prior gender dysphoria diagnosis.

This tally and others in the Komodo analysis are likely an undercount because they didn’t include treatment that wasn’t covered by insurance and were limited to pediatric patients with a gender dysphoria diagnosis. Practitioners may not log this diagnosis when prescribing treatment.

By suppressing sex hormones, puberty-blocking medications stop the onset of secondary sex characteristics, such as breast development and menstruation in adolescents assigned female at birth. For those assigned male at birth, the drugs inhibit development of a deeper voice and an Adam’s apple and growth of facial and body hair. They also limit growth of genitalia.

Without puberty blockers, such physical changes can cause severe distress in many transgender children. If an adolescent stops the medication, puberty resumes.

The medications are administered as injections, typically every few months, or through an implant under the skin of the upper arm.

After suppressing puberty, a child may pursue hormone treatments to initiate a puberty that aligns with their gender identity. Those for whom the opportunity to block puberty has already passed or who declined the option may also pursue hormone therapy.

At least 14,726 minors started hormone treatment with a prior gender dysphoria diagnosis from 2017 through 2021, according to the Komodo analysis.

Hormones – testosterone for adolescents assigned female at birth and estrogen for those assigned male – promote development of secondary sex characteristics. Adolescents assigned female at birth who take testosterone may notice that fat is redistributed from the hips and thighs to the abdomen. Arms and legs may appear more muscular. The brow and jawline may become more pronounced. Body hair may coarsen and thicken. Teens assigned male at birth who take estrogen may notice the hair on their body softens and thins. Fat may be redistributed from the abdomen to the buttocks and thighs. Their testicles may shrink and sex drive diminish. Some changes from hormone treatment are permanent.

Hormones are taken in a variety of ways: injections, pills, patches and gels. Some minors will continue to take hormones for many years well into adulthood, or they may stop if they achieve the physical traits they want.

Hormone treatment may leave an adolescent infertile, especially if the child also took puberty blockers at an early age. That and other potential side effects are not well-studied, experts say.

The ultimate step in gender-affirming medical treatment is surgery, which is uncommon in patients under age 18. Some children’s hospitals and gender clinics don’t offer surgery to minors, requiring that they be adults before deciding on procedures that are irreversible and carry a heightened risk of complications.

The Komodo analysis of insurance claims found 56 genital surgeries among patients ages 13 to 17 with a prior gender dysphoria diagnosis from 2019 to 2021. Among teens, “top surgery” to remove breasts is more common. In the three years ending in 2021, at least 776 mastectomies were performed in the United States on patients ages 13 to 17 with a gender dysphoria diagnosis, according to Komodo’s data analysis of insurance claims. This tally does not include procedures that were paid for out of pocket.

A note on the data

Komodo’s analysis draws on full or partial health insurance claims for about 330 million U.S. patients over the five years from 2017 to 2021, including patients covered by private health plans and public insurance like Medicaid. The data include roughly 40 million patients annually, ages 6 through 17, and comprise health insurance claims that document diagnoses and procedures administered by U.S. clinicians and facilities.

To determine the number of new patients who initiated puberty blockers or hormones, or who received an initial dysphoria diagnosis, Komodo looked back at least one year prior in each patient’s record. For the surgery data, Komodo counted multiple procedures on a single day as one procedure.

For the analysis of pediatric patients initiating puberty blockers or hormones, Komodo searched for patients with a prior gender dysphoria diagnosis. Patients with a diagnosis of central precocious puberty were removed. A total of 17,683 patients, ages 6 through 17, with a prior gender dysphoria diagnosis initiated either puberty blockers or hormones or both during the five-year period. Of these, 4,780 patients had initiated puberty blockers and 14,726 patients had initiated hormone treatment.

Youth in Transition

By Robin Respaut and Chad Terhune

Photo editing: Corrine Perkins

Art direction: John Emerson

Edited by Michele Gershberg and John Blanton

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Americans’ Complex Views on Gender Identity and Transgender Issues

Most favor protecting trans people from discrimination, but fewer support policies related to medical care for gender transitions; many are uneasy with the pace of change on trans issues, table of contents.

• A rising share say a person’s gender is determined by their sex at birth
• Many Americans point to science when asked what has influenced their views on whether gender can differ from sex assigned at birth
• Public sees discrimination against trans people and limited acceptance
• About four-in-ten say society has gone too far in accepting trans people
• Plurality of adults say views on gender identity issues are changing too quickly
• Most say they’re not paying close attention to news about bills related to transgender people 
• About six-in-ten would favor requiring that transgender athletes compete on teams that match their sex at birth
• Views on many policies related to transgender issues vary by age, party, and race and ethnicity 
• Sizable shares say forms and government documents should include options other than ‘male’ and ‘female’
• About three-in-ten parents of K-12 students say their children have learned about people who are trans or nonbinary at school 
• Acknowledgments
• The American Trends Panel survey methodology
• Panel recruitment
• Sample design
• Questionnaire development and testing
• Data collection protocol
• Data quality checks
• Dispositions and response rates
• A note about the Asian sample

Pew Research Center conducted this study to better understand Americans’ views about gender identity and people who are transgender or nonbinary. These findings are part of a larger project that includes findings from six focus groups on  the experiences and views of transgender and nonbinary adults  and estimates of the  share of U.S. adults who say their gender is different from the sex they were assigned at birth . 

This analysis is based on a survey of 10,188 U.S. adults. The data was collected as a part of a larger survey conducted May 16-22, 2022. Everyone who took part is a member of the Center’s American Trends Panel (ATP), an online survey panel that is recruited through national, random sampling of residential addresses. This way, nearly all U.S. adults have a chance of selection. The survey is weighted to be representative of the U.S. adult population by gender, race, ethnicity, partisan affiliation, education and other categories. Read more about the  ATP’s methodology . See here to read more about the  questions used for this report and the report’s methodology .

References to White, Black and Asian adults include only those who are not Hispanic and identify as only one race. Hispanics are of any race.

All references to party affiliation include those who lean toward that party. Republicans include those who identify as Republicans and those who say they lean toward the Republican Party. Democrats include those who identify as Democrats and those who say they lean toward the Democratic Party.

References to college graduates or people with a college degree comprise those with a bachelor’s degree or more. “Some college” includes those with an associate degree and those who attended college but did not obtain a degree.

The terms “transgender” and “trans” are used interchangeably throughout this report to refer to people whose gender is different from the sex they were assigned at birth.

As the United States addresses issues of transgender rights and the broader landscape around gender identity continues to shift, the American public holds a complex set of views around these issues, according to a new Pew Research Center survey.

Roughly eight-in-ten U.S. adults say there is at least some discrimination against transgender people in our society, and a majority favor laws that would protect transgender individuals from discrimination in jobs, housing and public spaces. At the same time, 60% say a person’s gender is determined by their sex assigned at birth, up from 56% in 2021 and 54% in 2017.

The public is divided over the extent to which our society has accepted people who are transgender: 38% say society has gone too far in accepting them, while a roughly equal share (36%) say society hasn’t gone far enough. About one-in-four say things have been about right. Underscoring the public’s ambivalence around these issues, even among those who see at least some discrimination against trans people, a majority (54%) say society has either gone too far or been about right in terms of acceptance.

The fundamental belief about whether gender can differ from sex assigned at birth is closely aligned with opinions on transgender issues. Americans who say a person’s gender  can  be different from their sex at birth are more likely than others to see discrimination against trans people and a lack of societal acceptance. They’re also more likely to say that our society hasn’t gone far enough in accepting people who are transgender. But even among those who say a person’s gender is determined by their sex at birth, there is a diversity of viewpoints. Half of this group say they would favor laws that protect trans people from discrimination in certain realms of life. And about one-in-four say forms and online profiles should include options other than “male” or “female” for people who don’t identify as either.   

Related:  The Experiences, Challenges and Hopes of Transgender and Nonbinary U.S. adults

When it comes to issues surrounding gender identity, young adults are at the leading edge of change and acceptance. Half of adults ages 18 to 29 say someone can be a man or a woman even if that differs from the sex they were assigned at birth. This compares with about four-in-ten of those ages 30 to 49 and about a third of those 50 and older. Adults younger than 30 are also more likely than older adults to say society hasn’t gone far enough in accepting people who are transgender (47% vs. 39% of 30- to 49-year-olds and 31% of those 50 and older) 

These views differ even more sharply by partisanship. Democrats and those who lean to the Democratic Party are more than four times as likely as Republicans and Republican leaners to say that a person’s gender can be different from the sex they were assigned at birth (61% vs. 13%). Democrats are also much more likely than Republicans to say our society hasn’t gone far enough in accepting people who are transgender (59% vs. 10%). For their part, 66% of Republicans say society has gone  too far  in accepting people who are transgender.

Amid a national conversation over these issues, many states are considering or have put in place  laws or policies  that would directly affect the lives of transgender and nonbinary people – that is, those who don’t identify as a man or a woman. Some of these laws would limit protections for transgender and nonbinary people; others are aimed at safeguarding them. The survey finds that a majority of U.S. adults (64%) say they would favor laws that would protect transgender individuals from discrimination in jobs, housing and public spaces such as restaurants and stores. But there is also a fair amount of support for specific proposals that would limit how trans people can participate in certain activities and navigate their day-to-day lives. 

Roughly six-in-ten adults (58%) favor proposals that would require transgender athletes to compete on teams that match the sex they were assigned at birth (17% oppose this, 24% neither favor nor oppose). 1 And 46% favor making it illegal for health care professionals to provide someone younger than 18 with medical care for a gender transition (31% oppose). The public is more evenly split when it comes to making it illegal for public school districts to teach about gender identity in elementary schools (41% favor and 38% oppose) and investigating parents for child abuse if they help someone younger than 18 get medical care for a gender transition (37% favor and 36% oppose). Across the board, views on these policies are deeply divided by party. 

When asked what has influenced their views on gender identity – specifically, whether they believe a person can be a different gender than the sex they were assigned at birth – those who believe gender can be different from sex at birth and those who do not point to different factors. For the former group, the most influential factors shaping their views are what they’ve learned from science (40% say this has influenced their views a great deal or a fair amount) and knowing someone who is transgender (38%). Some 46% of those who say gender is determined by sex at birth also point to what they’ve learned from science, but this group is far more likely than those who say a person’s gender can be different from their sex at birth to say their religious beliefs have had at least a fair amount of influence on their opinion (41% vs. 9%).   

The nationally representative survey of 10,188 U.S. adults was conducted May 16-22, 2022.  Previously published findings from the survey  show that 1.6% of U.S. adults are trans or nonbinary, and the share is higher among adults younger than 30. More than four-in-ten U.S. adults know someone who is trans and 20% know someone who is nonbinary. Among the other key findings in this report:

Nearly half of U.S. adults (47%) say it’s extremely or very important to use a person’s new name if they transition to a gender that is different from the sex they were assigned at birth and change their name.  A smaller share (34%) say the same about using someone’s new pronouns (such as “he” instead of “she”). A majority of Democrats (64%) – compared with 28% of Republicans – say it’s at least very important to use someone’s new name if they go through a gender transition and change their name. And while 51% of Democrats say it’s extremely or very important to use someone’s new pronouns, just 14% of Republicans say the same.

Many Americans express discomfort with the pace of change around issues of gender identity.  Some 43% say views on issues related to people who are transgender or nonbinary are changing too quickly, while 26% say things aren’t changing quickly enough and 28% say the pace of change is about right. Adults ages 65 and older are the most likely to say views on these issues are changing too quickly; conversely, those younger than 30 are the most likely to say they’re not changing quickly enough. 

More than four-in-ten (44%) say forms and online profiles that ask about a person’s gender should include options other than “male” and “female” for people who don’t identify as either.  Some 38% say the same about government documents such as passports and driver’s licenses. Half of adults younger than 30 say government documents that ask about a person’s gender should provide more than two gender options, compared with about four-in-ten or fewer among those in older age groups. Views differ even more widely by party: While majorities of Democrats say forms and online profiles (64%) and government documents (58%) should offer options other than “male” and “female,” about eight-in-ten Republicans say they should  not  (79% say this about forms and online profiles and 83% say this about government documents). 

Democrats and Republicans who agree that a person’s gender is determined by their sex at birth often have different views on transgender issues.  A majority (61%) of Democrats – but just 31% of Republicans – who say a person’s gender is determined by the sex they were assigned at birth say there is at least a fair amount of discrimination against transgender people in our society today. And while 62% of Democrats who say gender is determined by sex at birth say they would favor policies that protect trans individuals against discrimination, fewer than half of their Republican counterparts say the same. 

Democrats’ views on some transgender issues vary by age.  Among Democrats younger than 30, about seven-in-ten (72%) say someone can be a man or a woman even if that’s different from the sex they were assigned at birth, and 66% say society hasn’t gone far enough in accepting people who are transgender. Smaller majorities of Democrats 30 and older express these views. Age is less of a factor among Republicans. In fact, similar shares of Republicans ages 18 to 29 and those 65 and older say a person’s gender is determined by their sex at birth (88% each) and that society has gone too far in accepting people who are transgender (67% of Republicans younger than 30 and 69% of those 65 and older).  

About three-in-ten parents of K-12 students (29%) say at least one of their children has learned about people who are transgender or nonbinary from a teacher or another adult at their school.  Similar shares across regions and in urban, suburban and rural areas say their children have learned about this in school, as do similar shares of Republican and Democratic parents. Views on whether it’s good or bad that their children have or haven’t learned about people who are trans or nonbinary at school vary by party and by children’s age. For example, among parents of children in elementary school, 45% say either that their children  have  learned about this and that’s a  bad  thing or that they  haven’t  learned about it and that’s a  good  thing. A smaller share of parents of middle and high schoolers (34%) say the same. Republican parents are much more likely than Democratic parents to say this, regardless of their child’s age.

Six-in-ten U.S. adults say that whether a person is a man or a woman is determined by their sex assigned at birth. This is up from 56%  one year ago  and 54% in  2017 . No single demographic group is driving this change, and patterns in who is more likely to say this are similar to what they were in past years.

Today, half or more in all age groups say that gender is determined by sex assigned at birth, but this is a less common view among younger adults. Half of adults younger than 30 say this, lower than the 60% of 30- to 49-year-olds who say the same. Even higher shares of those 50 to 64 (66%) and those 65 and older (64%) say a person’s gender is determined by their sex at birth.

The party gap on this issue remains wide. The vast majority of Republicans and those who lean toward the GOP say gender is determined by sex assigned at birth (86%), compared with 38% of Democrats and Democratic leaners. Most Democrats say that whether a person is a man or a woman can be different from their sex at birth (61% vs. just 13% of Republicans). Liberal Democrats are particularly likely to hold this view – 79% say a person’s gender can be different from sex at birth, compared with 45% of moderate or conservative Democrats. Meanwhile, 92% of conservative Republicans say gender is determined by sex at birth and 74% of moderate or liberal Republicans agree.

Democrats ages 18 to 29 are also substantially more likely than older Democrats to say that someone’s gender can be different from their sex assigned at birth, although majorities of Democrats across age groups share this view. About seven-in-ten Democrats younger than 30 say this (72%), compared with about six-in-ten or fewer in the older age groups. Among Republicans, there is no clear pattern by age. About eight-in-ten or more Republicans across age groups – including 88% each among those ages 18 to 29 and those 65 and older – say a person’s gender is determined by their sex at birth. 

The view that a person’s gender is determined by their sex assigned at birth is more common among those with lower levels of educational attainment and those living in rural areas or in the Midwest or South. This view is also more prevalent among men and Black Americans. 

A solid majority of those who do  not  know a transgender person say that whether a person is a man or a woman is determined by sex assigned at birth (68%), while those who  do  know a trans person are more evenly split. About half say gender is determined by sex assigned at birth (51%), while 48% say gender and sex assigned at birth can be different. 

Though Republicans who know a trans person are more likely than Republicans who don’t to say gender can be different from sex assigned at birth, more than eight-in-ten in both groups (83% and 88%, respectively) say gender is determined by sex at birth. Meanwhile, there are large differences between Democrats who do and do  not  know a transgender person. A majority of Democrats who  do  know a trans person (72%) say someone can be a man or a woman even if that differs from their sex assigned at birth, while those who don’t know anyone who is transgender are about evenly split (48% say gender is determined by sex assigned at birth while 51% say it can be different). 

When asked about factors that have influenced their views about whether someone’s gender can be different from the sex they were assigned at birth, 44% say what they’ve learned from science has had a great deal or a fair amount of influence. About three-in-ten (28%) point to their religious views and about two-in-ten (22%) say knowing someone who is transgender has influenced their views at least a fair amount. Smaller shares say what they’ve heard or read in the news (15%) or on social media (14%) has had a great deal or a fair amount of influence on their views.

The factors people point to on this topic differ by whether or not they say gender is determined by sex at birth. Among those who say that whether someone is a man or a woman is determined by the sex they were assigned at birth, 46% say what they’ve learned from science has influenced their views on this at least a fair amount, while 41% say the same about their religious views. About one-in-ten point to what they’ve heard or read in the news (12%), what they’ve heard or read on social media (11%) or knowing someone who’s transgender (11%). 

Among those who say someone can be a man or a woman even if that’s different from the sex they were assigned at birth, 40% say their views on this topic have been influenced at least a fair amount by what they’ve learned from science. A similar share say the same about knowing a transgender person (38%). Smaller shares in this group say what they’ve heard or read in the news (19%) or on social media (18%) or their religious views (9%) have had a great deal or a fair amount of influence.

Among those who say gender is determined by sex assigned at birth, adults younger than 30 stand out as being more likely than their older counterparts to say their knowledge of science (60%), what they’ve heard or read on social media (22%) or knowing someone who is trans (17%) influenced this view a great deal or a fair amount. In turn, those ages 65 and older tend to be more likely than younger age groups to cite their religious views (51% in the older group say this has had at least a fair amount of influence). 

Republicans who say gender is determined by sex assigned at birth are more likely than Democrats with the same view to say their knowledge of science (52% vs. 40%) and their religious views (45% vs. 34%) have had at least a fair amount of influence, while Democrats are more likely than Republicans to say the news (17% vs. 10%), social media (16% vs. 10%) and knowing someone who is trans (15% vs. 9%) have influenced them – though the shares are still small among both groups.

On the flip side, among those who say someone’s gender can be  different  from the sex they were assigned at birth, adults younger than 30 are also more likely than older adults to say social media has contributed to this view at least a fair amount (33% vs. 15% or fewer among older age groups). Adults ages 65 and older are more likely than their younger counterparts to say what they’ve learned from science has influenced their view (46% vs. 40% or fewer). 

Democrats who say whether someone is a man or a woman can be different from their sex at birth are more likely than Republicans with the same view to say that what they’ve learned from science (43% vs. 26%) and knowing someone who is transgender (40% vs. 26%) has influenced their view a great deal or a fair amount.

Roughly eight-in-ten Americans say transgender people face at least some discrimination, and relatively few believe our society is extremely or very accepting of people who are trans. These views differ widely by partisanship and by beliefs about whether someone’s gender can differ from the sex they were assigned at birth.

Overall, 57% of adults say there is a great deal or a fair amount of discrimination against transgender people in our society today. An additional 21% say there is some discrimination against trans people, and 14% say there is a little or none at all. 

There are modest differences in views on this issue across demographic groups. Women (62%) are more likely than men (52%) to say there is a great deal or a fair amount of discrimination against transgender people, and college graduates (62%) are more likely than those with less education (55%) to say the same. 

There is, however, a wide partisan divide in these views: While 76% of Democrats and those who lean to the Democratic Party say there is a great deal or a fair amount of discrimination against trans people, 35% of Republicans and Republican leaners share that assessment. One-in-four Republicans see little or no discrimination against this group, compared with 5% of Democrats. 

These views are also linked with underlying opinions about whether a person’s gender can be different from their sex assigned at birth. Among those who say someone can be a man or a woman even if that’s different from the sex they were assigned at birth, 83% say there is a great deal or a fair amount of discrimination against trans people. Even so, some 42% of those who hold the alternative point of view – that gender is determined by sex assigned at birth – also see at least a fair amount of discrimination. Among Democrats who say gender is determined by sex at birth, that share rises to 61%. 

Relatively few adults (14%) say society is extremely or very accepting, while about a third (35%) say it is somewhat accepting. A plurality (44%) says our society is a little or not at all accepting of trans people. 

Again, these views are strongly linked with partisanship. Democrats have a much more negative view than Republicans, with 54% of Democrats saying society is a little accepting or not at all accepting of transgender people, compared with a third of Republicans. 

And, as with views of discrimination, assessments of societal acceptance are linked to underlying views about how gender is determined. Those who say one’s gender can be different from the sex they were assigned at birth see less acceptance: 56% say society is a little accepting or not accepting at all of people who are transgender. This compares with 37% among those who say gender is determined by sex at birth. Republicans who say gender is determined by sex at birth are more likely than Democrats who say the same to believe that society is at least somewhat accepting of people who are transgender (61% vs. 47%).

While a majority of Americans see at least a fair amount of discrimination against transgender people and relatively few see widespread acceptance, 38% say our society has gone too far in accepting them. Some 36% say society has not gone far enough in accepting people who are trans, and 23% say the level of acceptance has been about right.

These views differ along demographic and partisan lines. Young adults (ages 18 to 29) and those with a bachelor’s degree or more education are among the most likely to say society hasn’t gone far enough in accepting people who are trans. Men, White adults and those without a four-year college degree are among the most likely to say society has gone too far in this regard. 

There is a wide partisan divide as well. Roughly six-in-ten Democrats (59%) say society hasn’t gone far enough in accepting people who are transgender, while 15% say it has gone too far (24% say it’s been about right). Republicans’ views are almost the inverse: 10% say society hasn’t gone far enough and 66% say it’s gone too far (22% say it’s been about right). 

Even among those who see at least some discrimination against trans people, a majority (54%) say society has either gone too far in accepting trans people or been about right; 44% say society hasn’t gone far enough.

Many say it’s important to use someone’s new name, pronouns when they’ve gone through a gender transition

Nearly half of adults (47%) say it’s extremely or very important that if a person who transitions to a gender that’s different from their sex assigned at birth changes their name, others refer to them by their new name. An additional 22% say this is somewhat important. Three-in-ten say this is a little or not at all important (18%) or that it shouldn’t be done (12%).

Smaller shares say that if a person transitions to a gender that’s different from their sex assigned at birth and starts going by different pronouns (such as “she” instead of “he”), it’s important that others refer to them by their new pronouns. About a third (34%) say this is extremely or very important, and 21% say this is somewhat important. More than four-in-ten say this is a little or not at all important (26%) or it should not be done (18%).

These views differ along many of the same dimensions as other topics asked about. While 80% of those who believe someone’s gender can be different from their sex assigned at birth also say it’s extremely or very important to use a person’s new name when they’ve gone through a gender transition, 27% of those who think gender is determined by one’s sex assigned at birth share this opinion. The pattern is similar when it comes to use of preferred pronouns. 

Democrats are much more likely than Republicans to say it’s extremely or very important to refer to a person using their new name or pronouns. When it comes to pronouns, a majority of Republicans (55%), compared with only 17% of Democrats, say using someone’s new pronouns when they’ve been through a gender transition is not at all important or should not be done.  

There are some demographic differences as well, with women more likely than men and those with a four-year college degree more likely than those with less education to say it’s extremely or very important to use a person’s new name or pronouns when referring to them.

In addition, people who say they know someone who is trans are more likely than those who do not to say this is extremely or very important. Even so, substantial shares of those who don’t know a trans person view this as important. For example, 39% of those who don’t know someone who is transgender say it’s extremely or very important to refer to a person who goes through a gender transition and changes their name by their new name. 

Many Americans are not comfortable with the pace of change that’s occurring around issues involving gender identity. Some 43% say views on issues related to people who are transgender and nonbinary are changing too quickly. About one-in-four (26%) say things are not changing quickly enough, and 28% say they are changing at about the right speed.

Women (30%) are more likely than men (21%) to say views on these issues are not changing quickly enough, and adults younger than 30 are more likely than their older counterparts to say the same. Among those ages 18 to 29, 37% say views on these issues are not changing quickly enough; this compares with 26% of those ages 30 to 49, 22% of those ages 50 to 64 and 19% of those 65 and older. At the same time, White adults (46%) are more likely than Black (34%), Hispanic (39%) or Asian (31%) adults to say views are changing  too quickly .

Opinions also differ sharply by partisanship. Among Democrats, a plurality (42%) say views on issues involving transgender and nonbinary people are not changing fast enough, and 21% say they are changing too quickly. About a third (35%) say the speed is about right. By contrast, 70% of Republicans say views on these issues are changing too quickly, while only 7% say views aren’t changing fast enough. About one-in-five Republicans (21%) say they’re changing at about the right speed. 

Respondents were asked in an open-ended format why they think views are changing too quickly or not quickly enough, when it comes to issues surrounding transgender and nonbinary people. For those who say things are changing too quickly, responses fell into several different categories. Some indicated that new ways of thinking about gender were inconsistent with their religious beliefs. Others expressed concern that the long-term consequences of medical gender transitions are not well-known, or that changing views on gender identity are merely a fad that’s being pushed by the media. Still others said they worry that there’s too much discussion of these issues in schools these days.

For those who say views are not changing quickly enough, some pointed to discrimination and a lack of acceptance of trans and nonbinary people. Others pointed to legislative initiatives in some states aimed at restricting the rights of trans and nonbinary people. Many also said that too many people in our society aren’t open to change when it comes to these issues. 2

In their own words: Why do some people think views on issues related to transgender people and those who don’t identify as a man or a woman are changing  too quickly ?

General concerns about the pace of change

“The issue is so new to me I can’t keep up. I don’t know what to think about all of this new information. I’m baffled by so many changes.”

“It takes quite a bit of time for society to accept changes. I have not been aware of this issue for very long. I am relatively conservative and feel that changes need time to be accepted.”

Religious reasons

“People now believe everyone should just forget about their birth identity and just go along with what they think they are. God made us all for a reason and if He intended us to pick our gender then there would be no reason to be born with specific male or female parts .”

“I have a personal religious belief that sex is an essential part of our eternal identity and that identifying as something other than you are … just doesn’t make a lot of sense.”

“I believe GOD created a man and a woman. We have overstepped our bounds in messing with the miracle of life. I side with my creator.”

Concerns about long-term medical consequences

“We do not know the long-term health problems of hormone therapy, especially in young children.”

“More time needs to pass to study mental, physical, emotional ramifications of medications & surgeries, especially when done before puberty and/or adulthood.”

“Accepting gender fluidity, especially for younger children, seems quick. Also, medical treatments related to gender for people under 18 seems to be being accepted without longer term studies.”

It’s a fad/Driven by the media

“I respect people’s views about themselves, and I will refer to them in the way they want to be referred to, but I believe it’s become trendy because it’s being pushed so much in culture, especially for children.”

“News media, social media and entertainment media companies are trying to change, and it seems they have been succeeding in changing public opinion on this issue for many people.”

“It is encouraging kids who are easily influenced to participate in the ‘in’ fad when their brains are not fully developed.”

Concerns about schools

“Elementary school students should not be subjected to instruction on sex identity, any questions the child asks should be referred to a parent.”

“I think that young people are exposed to these issues at too early an age. I believe that it is up to the parents, and I oppose schools that want to include it in the ‘curriculum.’”

“It’s being pushed on society and especially on younger children, confusing them all the more. This is not something that should be taught in schools.”

In their own words: Why do some people think views on issues related to transgender people and those who don’t identify as a man or a woman are changing  too slowly ?

Discrimination

“There is far too much discrimination, hate, and violence directed toward people who are brave enough to stand up for who they truly are. We, as a country and as a society, need to respect how people want to identify themselves and be kind toward one another, end of story.”

“Protections for basic rights to self-determination in identity, health care choices, privacy, and consensual relationships should be a bare minimum that our society can provide for everyone – transgender people included . ”

“There’s too much discrimination. People need to quit controlling other people’s private lives. I consider them very brave for having the courage to be who they identify with . ”

“Equal protection has not kept up with trans issues, including trans youth and the right to gender-affirming care.”

Legislative efforts

“Acceptance is not changing quick enough. There remains discrimination and elected officials are passing laws that make it more difficult for transgender individuals in society to live, work and exist.”

“We are going backwards with all the anti-gay & -trans legislation that is being passed.”

“For every step forward, it feels like there are two steps back with reactive conservative laws.”

“These laws are working to restrict the rights of trans and nonbinary people, and also discrimination is still very high which results in elevated rates of suicide, poverty, violence and homelessness especially for people of color.”

“The spate of laws being proposed that would take away the rights of transgender people is evidence that we’re a long way from treating them right.”

Society is not open to change

“Too many people are simply stuck in the binary. We, as a society, need to just accept that someone else’s gender identity is whatever they say it is and it rarely has any bearing on the lives of others.”

“These are people. Who they say they are is all that matters. Society, mostly conservatives, doesn’t understand change in any form. So, they fight it. And they hinder the ability for others to learn about themselves and others, which slows growing as a society to a crawl.” 

“It’s an issue that has been in the closet for centuries. It’s time to acknowledge and accept that gender identity is a spectrum and not binary.” 

“We are not accepting the changes. We refuse to see what is in front of us. We care too much about not changing the status quo as we know it.” 

“Society often views this as a phase or a period of uncertainty in their life. Instead, it’s about a person bringing their gender identity in line with what they have experienced internally all their life.”

Many states are  considering legislation  related to people who are transgender, but a relatively small share of U.S. adults (8%) say they’re following news about these bills extremely or very closely. Another 24% say they’re following this somewhat closely, while about two-thirds say they’re following it either a little closely (23%) or not all closely (44%). 3

Only about one-in-ten or less across age, racial and ethnic groups, and across levels of educational attainment, say they are following news about bills related to people who are transgender extremely or very closely. Six-in-ten or more across demographic groups say they’re following news about these bills a little closely or not closely at all. 

Liberal Democrats and Democratic-leaning independents (46%) are more likely than moderate and conservative Democrats (29%) to say they are following news about state bills related to people who are transgender at least somewhat closely. Conservative Republicans and Republican leaners (31%) are more likely than their moderate and liberal counterparts (24%) – but less likely than liberal Democrats – to be following news about these bills at least somewhat closely. Still, half or more among each of these groups say they have been following news about this a little or not at all closely. 

The survey asked respondents how they feel about some current laws and policies that are either in place or being considered across the U.S. related to transgender issues. Only two of seven items are either endorsed or rejected by a majority: 64% say they would favor policies that protect transgender individuals from discrimination in jobs, housing, and public spaces such as restaurants and stores, and 58% say they would favor policies that require that transgender athletes compete on teams that match the sex they were assigned at birth rather than the gender they identify with. 

Even though there is not a majority consensus on most of these laws or policies, there are gaps of at least 10 percentage points on three items. Some 46% say they would favor making it illegal for health care professionals to provide someone younger than 18 with medical care for gender transitions, and 41% would favor requiring transgender individuals to use public bathrooms that match the sex they were assigned at birth rather than the gender they identify with; 31% say they would oppose each of these. Meanwhile, more say they would  oppose  (44%) than say they would favor (27%) requiring health insurance companies to cover medical care for gender transitions. 

Views are more divided when it comes to laws and policies that would make it illegal for public school districts to teach about gender identity in elementary schools (41% favor and 38% oppose) or that would investigate parents for child abuse if they helped someone younger than 18 get medical care for a gender transition (37% favor and 36% oppose). Some 21% and 27%, respectively, say they’d neither favor nor oppose these policies. 

Majorities of U.S. adults across age groups express support for laws and policies that would protect transgender individuals from discrimination in jobs, housing, and public spaces such as restaurants and stores. About seven-in-ten adults ages 18 to 29 (70%) and 30 to 49 (68%) say they favor such protections, as do about six-in-ten adults ages 50 to 64 (60%) and 65 and older (59%). 

But adults younger than 30 are more likely than those in each of the older age groups to say they favor laws or policies that would require health insurance companies to cover medical care for gender transitions (37% among those younger than 30 vs. about a quarter among each of the older age groups). They’re also less likely than older adults to express support for bills and policies that would restrict the rights of people who are transgender or limit what schools teach about gender identity. On most items, those ages 50 to 64 and those 65 and older express similar views. 

Views differ even more widely along party lines. For example, eight-in-ten Democrats say they favor laws or policies that would protect trans individuals from discrimination, compared with 48% of Republicans. Conversely, by margins of about 40 percentage points or more, Republicans are more likely than Democrats to express support for laws or policies that would do each of the following: require trans athletes to compete on teams that match the sex they were assigned at birth (85% of Republicans vs. 37% of Democrats favor); make it illegal for health care professionals to provide someone younger than 18 with medical care for a gender transition (72% vs. 26%); make it illegal for public school districts to teach about gender identity in elementary schools (69% vs. 18%); require transgender individuals to use public bathrooms that match the sex they were assigned at birth (67% vs. 20%); and investigate parents for child abuse if they help someone younger than 18 get medical care for a gender transition (59% vs. 17%). 

Overall, White adults tend to be more likely than Black, Hispanic and Asian adults to express support for laws and policies that would restrict the rights of transgender people or limit what schools can teach about gender identity. But among Democrats, White adults are often  less  likely than other groups to favor such laws and policies, particularly compared with their Black and Hispanic counterparts. And White Democrats are more likely than Black, Hispanic and Asian Democrats to say they favor protecting trans individuals from discrimination and requiring health insurance companies to cover medical care for gender transitions. 

About four-in-ten Americans (38%) say government documents such as passports and driver’s licenses that ask about a person’s gender should include options other than “male” and “female” for people who don’t identify as either; a larger share (44%) say the same about forms and online profiles that ask about a person’s gender.

Half of adults younger than 30 say government documents that ask about gender should include options other than “male” and “female,” compared with 39% of those ages 30 to 49, 35% of those 50 to 64 and 33% of adults 65 and older. When it comes to forms and online profiles, 54% of adults younger than 30 and 47% of those ages 30 to 49 say these forms should include more than two gender options; smaller shares of adults ages 50 to 64 and 65 and older (37% each) say the same. 

Views on this vary considerably by party. A majority of Democrats and Democratic-leaning independents say forms and online profiles (64%) and government documents (58%) that ask about a person’s gender should include options other than “male” and “female.” In contrast, about eight-in-ten or more Republicans and Republican leaners say forms and online profiles (79%) and government documents (83%) should  not  include more than these two gender options. 

Those who say they know someone who is nonbinary are more likely than those who don’t know anyone who’s nonbinary to say forms and government documents should include gender options other than “male” and “female.” Still, 39% of those who don’t know anyone who’s nonbinary say forms and online profiles shouldinclude other gender options, and 33% say the same about government documents that ask about a person’s gender. Conversely, 31% of those who say they know someone who’s nonbinary say forms and online profiles should  not  include options other than “male” and “female,” and 41% say this about government documents. 

In recent months, lawmakers in several states have introduced legislation that would  prohibit or limit instruction on sexual orientation or gender identity  in schools. The survey asked parents of K-12 students whether any of their children have learned about people who are transgender or who don’t identify as a boy or a girl from a teacher or another adult at their school and how they feel about the fact that their children have or have not learned about this.

Some 37% of parents with children in middle or high school say their middle or high schoolers have learned about people who are transgender or who don’t identify as a boy or a girl from a teacher or another adult at their school; a much smaller share of parents of elementary school students (16%) say the same. Overall, 29% of parents with children in elementary, middle or high school say at least one of their K-12 children have learned about this at school. 

Similar shares of parents of K-12 students in urban (31%), suburban (27%) and rural (32%) areas – and in the Northeast (34%), Midwest (33%), South (26%) and West (28%) – say their school-age children have learned about people who are transgender or who don’t identify as a boy or a girl. And Republican (27%) and Democratic (31%) parents are also about equally likely to say their children have learned about this in school. None of these differences are statistically significant.

Many parents of K-12 students don’t think it’s good for their children to learn about people who are transgender or nonbinary from their teachers or other adults at school. Among parents of elementary school students, 45% either say their children have learned about people who are trans or nonbinary at school and see this is a  bad  thing or say their children have  not  learned about this and say this is a  good  thing. A far smaller share (13%) say it’s a good thing that their elementary school children have learned about people who are trans or nonbinary or that it’s a bad thing that they  haven’t  learned about this. And about four-in-ten (41%) say it’s neither good nor bad that their elementary school children have or haven’t learned about people who are transgender or nonbinary. 

Among parents with children in middle or high school, 34% say it’s a bad thing that their children have learned about people who are trans or nonbinary at school  or  that it’s a good thing that they haven’t; 14% say it’s good that their middle or high schoolers have learned about this  or  that it’s bad that they haven’t; and 51% say it’s neither good nor bad that their children have or haven’t learned about this in school. 

Republican and Republican-leaning parents with children in elementary, middle and high school are more likely than their Democratic and Democratic-leaning counterparts to say it’s a bad thing that their children have learned about people who are trans or nonbinary at school or that it’s a good thing that they haven’t. In turn, Democratic parents are more likely to say it’s  good  that their children  have  learned about this or  bad  that they  haven’t . They are also more likely to say it’s neither good nor bad that their children have or haven’t learned about people who are trans or nonbinary at school. 

• For each policy item, respondents were also given the option of answering “neither favor nor oppose.”  ↩
• Open-ended responses (quotations) have been lightly edited for clarity and length. ↩
• The shares who say they are following news about this a little or not at all closely do not add up to the combined share shown in the chart due to rounding.  ↩

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May 12, 2022

What the Science on Gender-Affirming Care for Transgender Kids Really Shows

Laws that ban gender-affirming treatment ignore the wealth of research demonstrating its benefits for trans people’s health

By Heather Boerner

As attacks against transgender kids increase in the U.S., Minnesotans hold a rally at the state’s capitol in Saint Paul in March 2022 to support trans kids in Minnesota and Texas and around the country.

Michael Siluk/UCG/Universal Images Group via Getty Images

Editor’s Note (3/30/23): This article from May 2022 is being republished to highlight the ways that ongoing anti-trans legislation is harmful and unscientific.

For the first 40 years of their life, Texas resident Kelly Fleming spent a portion of most years in a deep depression. As an adult, Fleming—who uses they/them pronouns and who asked to use a pseudonym to protect their safety—would shave their face in the shower with the lights off so neither they nor their wife would have to confront the reality of their body.

What Fleming was experiencing, although they did not know it at the time, was gender dysphoria : the acute and chronic distress of living in a body that does not reflect one’s gender and the desire to have bodily characteristics of that gender. While in therapy, Fleming discovered research linking access to gender-affirming hormone therapy with reduced depression in transgender people. They started a very low dose of estradiol, and the depression episodes became shorter, less frequent and less intense. Now they look at their body with joy.

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So when Fleming sees what authorities in Texas , Alabama , Florida and other states are doing to bar transgender teens and children from receiving gender-affirming medical care, it infuriates them. And they are worried for their children, ages 12 and 14, both of whom are agender—a identity on the transgender spectrum that is neither masculine nor feminine.

“I’m just so excited to see them being able to present themselves in a way that makes them happy,” Fleming says. “They are living their best life regardless of what others think, and that’s a privilege that I did not get to have as a younger person.”

Laws Based on “Completely Wrong” Information

Currently more than a dozen state legislatures  or administrations are considering—or have already passed—laws banning health care for transgender young people. On April 20 the Florida Department of Health issued guidance to withhold such gender-affirming care. This includes social gender transitioning—acknowledging that a young person is trans, using their correct pronouns and name, and supporting their desire to live publicly as the gender of their experience rather than their sex assigned at birth. This comes nearly two months after Texas Governor Greg Abbott issued an order for the Texas Department of Family and Protective Services to investigate for child abuse parents who allow their transgender preteens and teenagers to receive medical care. Alabama recently passed SB 184 , which would make it a felony to provide gender-affirming medical care to transgender minors. In Alabama, a “minor” is defined as anyone 19 or younger.

If such laws go ahead, 58,200 teens in the U.S. could lose access to or never receive gender-affirming care, according to the Williams Institute at the University of California, Los Angeles. A decade of research shows such treatment reduces depression, suicidality and other devastating consequences of trans preteens and teens being forced to undergo puberty in the sex they were assigned at birth).

The bills are based on “information that’s completely wrong,” says Michelle Forcier, a pediatrician and professor of pediatrics at Brown University. Forcier literally helped write the book on how to provide evidence-based gender care to young people. She is also an assistant dean of admissions at the Warren Alpert Medical School of Brown University. Those laws “are absolutely, absolutely incorrect” about the science of gender-affirming care for young people, she says. “[Inaccurate information] is there to create drama. It’s there to make people take a side.”

The truth is that data from more than a dozen studies of more than 30,000 transgender and gender-diverse young people consistently show that access to gender-affirming care is associated with better mental health outcomes—and that lack of access to such care is associated with higher rates of suicidality, depression and self-harming behavior. (Gender diversity refers to the extent to which a person’s gendered behaviors, appearance and identities are culturally incongruent with the sex they were assigned at birth. Gender-diverse people can identify along the transgender spectrum, but not all do.) Major medical organizations, including the American Academy of Pediatrics (AAP) , the American Academy of Child and Adolescent Psychiatry , the Endocrine Society , the American Medical Association , the American Psychological Association and the American Psychiatric Association , have published policy statements and guidelines on how to provide age-appropriate gender-affirming care. All of those medical societies find such care to be evidence-based and medically necessary.

AAP and Endocrine Society guidelines call for developmentally appropriate care, and that means no puberty blockers or hormones until young people are already undergoing puberty for their sex assigned at birth. For one thing, “there are no hormonal differences among prepubertal children,” says Joshua Safer, executive director of the Mount Sinai Center for Transgender Medicine and Surgery in New York City and co-author of the Endocrine Society’s guidelines. Those guidelines provide the option of gonadotropin-releasing hormone analogues (GnRHas), which block the release of sex hormones, once young people are already into the second of five puberty stages—marked by breast budding and pubic hair. These are offered only if a teen is not ready to make decisions about puberty. Access to gender-affirming hormones and potential access to gender-affirming surgery is available at age 16—and then, in the case of transmasculine youth, only mastectomy, also known as top surgery. The Endocrine Society does not recommend genital surgery for minors.

Before puberty, gender-affirming care is about supporting the process of gender development rather than directing children through a specific course of gender transition or maintenance of cisgender presentation, says Jason Rafferty, co-author of AAP’s policy statement on gender-affirming care and a pediatrician and psychiatrist at Hasbro Children’s Hospital in Rhode Island. “The current research suggests that, rather than predicting or preventing who a child might become, it’s better to value them for who they are now—even at a young age,” Rafferty says.

A Safe Environment to Explore Gender

A 2021 systematic review of 44 peer-reviewed studies found that parent connectedness, measured by a six-question scale asking about such things as how safe young people feel confiding in their guardians or how cared for they feel in the family, is associated with greater resilience among teens and young adults who are transgender or gender-diverse. Rafferty says he sees his role with regard to prepubertal children as offering a safe environment for the child to explore their gender and for parents to ask questions. “The gender-affirming approach is not some railroad of people to hormones and surgery,” Safer says. “It is talking and watching and being conservative.”

Only once children are older, and if the incongruence between the sex assigned to them at birth and their experienced gender has persisted, does discussion of medical transition occur. First a gender therapist has to diagnose the young person with gender dysphoria .

After a gender dysphoria diagnosis—and only if earlier conversations suggest that hormones are indicated—guidelines call for discussion of fertility, puberty suppression and hormones. Puberty-suppressing medications have been used for decades for cisgender children who start puberty early, but they are not meant to be used indefinitely. The Endocrine Society guidelines recommend a maximum of two years on GnRHa therapy to allow more time for children to form their gender identity before undergoing puberty for their sex assigned at birth, the effects of which are irreversible.

“[Puberty blockers] are part of the process of ‘do no harm,’” Forcier says, referencing a popular phrase that describes the Hippocratic Oath, which many physicians recite a version of before they begin to practice.

Hormone blocker treatment may have side effects. A 2015 longitudinal observational cohort study of 34 transgender young people found that, by the time the participants were 22 years old, trans women experienced a decrease in bone mineral density. A 2020 study of puberty suppression in gender-diverse and transgender young people found that those who started puberty blockers in early puberty had lower bone mineral density before the start of treatment than the public at large. This suggests, the authors wrote, that GnRHa use may not be the cause of low bone mineral density for these young people. Instead they found that lack of exercise was a primary factor in low bone-mineral density, especially among transgender girls.

Other side effects of GnRHa therapy include weight gain, hot flashes and mood swings. But studies have found that these side effects—and puberty delay itself—are reversible , Safer says.

Gender-affirming hormone therapy often involves taking an androgen blocker (a chemical that blocks the release of testosterone and other androgenic hormones) and estrogen in transfeminine teens, and testosterone supplementation in transmasculine teens. Such hormones may be associated with some physiological changes for adult transgender people. For instance, transfeminine people taking estrogen see their so-called “good” cholesterol increase. By contrast, transmasculine people taking testosterone see their good cholesterol decrease. Some studies have hinted at effects on bone mineral density, but these are complicated and also depend on personal, family history, exercise, and many other factors in addition to hormones.”

And while some critics point to decade-old study and older studies suggesting very few young people persist in transgender identity into late adolescence and adulthood, Forcier says the data are “misleading and not accurate.” A recent review detailed methodological problems with some of these studies . New research in 17,151 people who had ever socially transitioned found that 86.9 percent persisted in their gender identity. Of the 2,242 people who reported that they reverted to living as the gender associated with the sex they were assigned at birth, just 15.9 percent said they did so because of internal factors such as questioning their experienced gender but also because of fear, mental health issues and suicide attempts. The rest reported the cause was social, economic and familial stigma and discrimination. A third reported that they ceased living openly as a trans person because doing so was “just too hard for me.”

The Harms of Denying Care

Data suggest the effects of denying that care are worse than whatever side effects result from delaying sex-assigned-at-birth puberty. And medical society guidelines conclude that the benefits of gender-affirming care outweigh the risks. Without gender-affirming hormone therapy, cisgender hormones take over, forcing body changes that can be permanent and distressing.

A 2020 study of 300 gender-incongruent young people found that mental distress—including self-harm, suicidal thoughts and depression— increased as the children were made to proceed with puberty according to their assigned sex. By the time 184 older teens (with a median age of 16) reached the stage in which transgender boys began their periods and grew breasts and transgender girls’ voice dropped and facial hair began to appear, 46 percent had been diagnosed with depression, 40 percent had self-harmed, 52 percent had considered suicide, and 17 percent had attempted it—rates significantly higher than those of gender-incongruent children who were a median of 13.9 years old or of cisgender kids their own age.

Conversely, access to gender-affirming hormones in adolescence appears to have a protective effect. In one study, researchers followed 104 teens and young adults for a year and asked them about their depression, anxiety and suicidality at the time they started receiving hormones or puberty blockers and again at the three-month, six-month and one-year mark. At the beginning of the study, which was published in JAMA Network Open in February 2022, more than half of the respondents reported moderate to severe depression, half reported moderate to severe anxiety, and 43.3 percent reported thoughts of self-harm or suicide in the past two weeks.

But when the researchers analyzed the results based on the kind of gender-affirming care the teens had received, they found that those who had access to puberty blockers or gender-affirming hormones were 60 percent less likely to experience moderate to severe depression. And those with access to the medical treatments were 73 percent less likely to contemplate self-harm or suicide.

“Delays in prescribing puberty blockers and hormones may in fact worsen mental health symptoms for trans youth,” says Diana Tordoff, an epidemiology graduate student at the University of Washington and co-author of the study.

That effect may be lifelong. A 2022 study of more than 21,000 transgender adults showed that just 41 percent of adults who wanted hormone therapy received it, and just 2.3 percent had access to it in adolescence. When researchers looked at rates of suicidal thinking over the past year in these same adults, they found that access to hormone therapy in early adolescence was associated with a 60 percent reduction in suicidality in the past year and that access in late adolescence was associated with a 50 percent reduction.

For Fleming’s kids in Texas, gender-affirming hormones are not currently part of the discussion; not all trans people desire hormones or surgery to feel affirmed in their gender. But Fleming is already looking at jobs in other states to protect their children’s access to such care, should they change their mind. “Getting your body closer to the gender [you] identify with—that is what helps the dysphoria,” Fleming says. “And not giving people the opportunity to do that, making it harder for them to do that, is what has made the suicide rate among transgender people so high. We just—trans people are just trying to survive.”

IF YOU NEED HELP If you or someone you know is struggling or having thoughts of suicide, help is available. Call the National Suicide Prevention Lifeline at 1-800-273-8255 (TALK), use the online Lifeline Chat or contact the Crisis Text Line by texting TALK to 741741.

The Evidence for Trans Youth Gender-Affirming Medical Care

Research suggests gender-affirming medical care results in better mental health..

Posted January 24, 2022 | Reviewed by Abigail Fagan

• Sixteen studies to date have examined the impact of gender-affirming medical care for transgender youth.
• Existing evidence suggests that gender-affirming medical care results in favorable mental health outcomes.
• All major medical organizations oppose legislation that would ban gender-affirming medical care for transgender adolescents.

NOTE: This post was updated on October 11, 2022. In discussions of studies 5, 7, 8 and 10, the final sentence was appended to include further information about the study.

I'm a physician-scientist who studies the mental health of transgender and gender diverse youth. I also spend a lot of time on Twitter . And yes I know, that's my first mistake. I've noticed there seem to be hundreds if not thousands of Twitter accounts that will repeatedly post that there is no evidence that gender-affirming medical care results in good mental health outcomes for transgender youth.

Since several U.S. states are introducing legislation to outlaw gender-affirming medical care this year (despite opposition from just about every major medical organization including The American Medical Association, The American Academy of Pediatrics, and The American Psychiatric Association), I thought this was a good time to review the relevant research for you all. So buckle up — here we go. The studies are in chronological order. I'll provide a brief summary of each and provide the citation for people who want to read more. I'll plan on updating this post as new studies become available. As you read, please keep in mind that all studies have methodological strengths and weaknesses and conclusions must be drawn from all of these studies together.

The Studies

Study 1: De Vries, A. L., Steensma, T. D., Doreleijers, T. A., & Cohen‐Kettenis, P. T. (2011). Puberty suppression in adolescents with gender identity disorder: A prospective follow‐up study. The Journal of Sexual Medicine, 8(8), 2276-2283.

This study from the Netherlands followed 70 transgender adolescents and measured their mental health before and after pubertal suppression. Study participants had improvements in depression and global functioning following treatment. However, feelings of anxiety and anger , gender dysphoria , and body satisfaction did not change.

Study 2: De Vries, A. L., McGuire, J. K., Steensma, T. D., Wagenaar, E. C., Doreleijers, T. A., & Cohen-Kettenis, P. T. (2014). Young adult psychological outcome after puberty suppression and gender reassignment. Pediatrics, 134(4), 696-704.

Another study from the Netherlands. This one followed 55 transgender adolescents through pubertal suppression, gender-affirming hormone treatment ( estrogen or testosterone ), and gender-affirming genital surgery (as adults). Of note, many of these participants were also participants in study 1 (this study followed them for longer). The researchers found that psychological functioning steadily improved over the course of the study and by adulthood these now young adults had global functioning scores similar to or better than age-matched peers in the general population. Of note, one patient in this study died from a surgical complication of vaginoplasty (necrotizing fasciitis), but little additional information is provided.

Study 3: Costa, R., Dunsford, M., Skagerberg, E., Holt, V., Carmichael, P., & Colizzi, M. (2015). Psychological support, puberty suppression, and psychosocial functioning in adolescents with gender dysphoria. The Journal of Sexual Medicine, 12(11), 2206-2214.

This study is from the United Kingdom. They followed 101 adolescents who received pubertal suppression at the beginning of the study and 100 adolescents who, for a range of reasons, were deemed by the team not ready to start pubertal suppression and thus did not receive it over the course of the study. Both groups received supportive psychotherapy . Both groups saw improvement in mental health. While the pubertal suppression group had a 5-point higher mean score on the study's psychological functioning scale at the end of the study, the difference was not statistically significant. This could have been due to the small sample size by the end of the study (the researchers only had data from 36 participants in the therapy-only group and 35 participants in the pubertal suppression group at the final time point of the study). We will see that later studies were able to obtain larger sample sizes so that statistically significant differences between those who did and did not receive pubertal suppression could be detected.

Study 4: Allen, L. R., Watson, L. B., Egan, A. M., & Moser, C. N. (2019). Well-being and suicidality among transgender youth after gender-affirming hormones. Clinical Practice in Pediatric Psychology, 7(3), 302.

This study was from researchers at Children's Mercy Hospital Gender Pathway Services Clinic in Missouri. They followed 47 transgender adolescents who received gender-affirming hormones (estrogen or testosterone) to a mean 349 days after starting treatment. They found statistically significant increases in general well-being and a statistically significant decrease in suicidality. Of note, the adolescents also received psychotherapy.

Study 5: Kaltiala, R., Heino, E., Työläjärvi, M., & Suomalainen, L. (2020). Adolescent development and psychosocial functioning after starting cross-sex hormones for gender dysphoria. Nordic Journal of Psychiatry, 74(3), 213-219.

This study is from Finland. Researchers conducted a retrospective chart review of 52 adolescents who received gender-affirming hormones (estrogen or testosterone) and found statistically significant decreases in need for specialist level psychiatric treatment for depression (decreased from 54% to 15%), anxiety (decreased from 48% to 15%), and suicidality or self-harm (decreased from 35% to 4%) following treatment. However, the authors note that gender reassignment is "not enough to improve functioning and relieve psychiatric comorbidities among adolescents with gender dysphoria."

Study 6: de Lara, D. L., Rodríguez, O. P., Flores, I. C., Masa, J. L. P., Campos-Muñoz, L., Hernández, M. C., & Amador, J. T. R. (2020). Psychosocial assessment in transgender adolescents. Anales de Pediatría (English Edition), 93(1), 41-48.

This study is from Spain. It followed 23 transgender adolescents who received gender-affirming hormones (estrogen or testosterone) and 30 cisgender controls for approximately one year. They found the transgender adolescents at baseline had worse measures of mental health than the cisgender control adolescents but that this difference equalized by the end of the study. The transgender adolescents in the study who received gender-affirming hormones had statistically significant improvements in several mental health measures, including anxiety and depression.

Study 7: van der Miesen, A. I., Steensma, T. D., de Vries, A. L., Bos, H., & Popma, A. (2020). Psychological functioning in transgender adolescents before and after gender-affirmative care compared with cisgender general population peers. Journal of Adolescent Health, 66(6), 699-704.

This was another Dutch study, with an impressive sample size. Researchers compared 272 transgender adolescents referred to the gender clinic who had not yet received pubertal suppression with 178 transgender adolescents who had received pubertal suppression. They found those who received pubertal suppression had better mental health outcomes than those who did not receive pubertal suppression. However, because subjects received psychotherapy, the authors note that the study does not provide "direct evidence" that pubertal suppression improves mental health in transgender youth.

Study 8: Achille, C., Taggart, T., Eaton, N. R., Osipoff, J., Tafuri, K., Lane, A., & Wilson, T. A. (2020). Longitudinal impact of gender-affirming endocrine intervention on the mental health and well-being of transgender youths: preliminary results. International Journal of Pediatric Endocrinology, 2020(1), 1-5.

This study was from Stony Brook Children's Hospital in New York. It followed 50 transgender adolescents longitudinally. Over the course of the study, 23 received pubertal suppression only, 35 received gender-affirming hormones only, and 11 received both. Three participants received no gender-affirming medical interventions. Over the course of the study, there was a statistically significant decrease in depression scores in one group: Male-to-female transitioners who underwent puberty suppression only.

Study 9: Kuper, L. E., Stewart, S., Preston, S., Lau, M., & Lopez, X. (2020). Body dissatisfaction and mental health outcomes of youth on gender-affirming hormone therapy. Pediatrics, 145(4).

This study was from a gender clinic in Dallas, Texas. The researchers followed 148 transgender adolescents who were receiving gender-affirming medical treatment. 25 received pubertal suppression only, 93 received gender-affirming hormones (estrogen or testosterone) only, and 30 received both. 15 participants received gender-affirming chest surgery. When examining all participants together, the study found statistically significant improvements in body dissatisfaction, depressive symptoms, and anxiety symptoms.

Study 10: Turban, J. L., King, D., Carswell, J. M., & Keuroghlian, A. S. (2020). Pubertal suppression for transgender youth and risk of suicidal ideation. Pediatrics, 145(2).

This study was conducted by myself along with several other researchers from Harvard Medical School. It utilized data from a non-probability sample of 20,619 transgender adults who reported ever wanting pubertal suppression. Of these, 89 actually received pubertal suppression. After adjusting for potentially confounding variables , access to pubertal suppression was associated with a lower odds of lifetime suicidal ideation. Of note, this study did not identify psychotherapy as a potentially confounding variable.

Study 11: Carmichael, P., Butler, G., Masic, U., Cole, T. J., De Stavola, B. L., Davidson, S., ... & Viner, R. M. (2021). Short-term outcomes of pubertal suppression in a selected cohort of 12 to 15 year old young people with persistent gender dysphoria in the UK. PLoS One, 16(2), e0243894.

This is another study from the United Kingdom. Researchers presented data for transgender adolescents who had received pubertal suppression. They had data for 44 patients after 12 months of treatment, 24 patients after 24 months of treatment, and 14 patients after 36 months of treatment. They were unable to detect any changes on their mental health measures (positive or negative).

Study 12: Grannis, C., Leibowitz, S. F., Gahn, S., Nahata, L., Morningstar, M., Mattson, W. I., ... & Nelson, E. E. (2021). Testosterone treatment, internalizing symptoms, and body image dissatisfaction in transgender boys. Psychoneuroendocrinology, 132, 105358.

This study recruited 42 birth-assigned female adolescents from a gender clinic in Ohio. Nineteen were receiving testosterone and 23 were not. Those not receiving testosterone were not receiving it due to a number of reasons (referred to endocrinology but hadn't started, parents not providing consent, and one was not interested in testosterone). The adolescents who were receiving testosterone treatment had lower scores on measures of generalized anxiety, social anxiety , depression, and body image dissatisfaction.

Study 13: Hisle-Gorman, E., Schvey, N. A., Adirim, T. A., Rayne, A. K., Susi, A., Roberts, T. A., & Klein, D. A. (2021). Mental healthcare utilization of transgender youth before and after affirming treatment. The Journal of Sexual Medicine, 18(8), 1444-1454.

This study utilized military healthcare data from transgender youth who received medical care through the U.S. military healthcare system. The researchers identified 963 transgender adolescents who had received some form of gender-affirming medical treatment. The mean age of starting any gender-affirming medical care was 18.2 (so this study may not technically qualify for our review of studies of adolescents). Their outcomes of interest were number of mental healthcare visits after gender-affirming medical care and number of days taking a psychiatric medication after starting gender-affirming medical care. In their adjusted models, there was no change in number of annual mental healthcare visits and an increase in days taking psychiatric medication from a mean 120 days per year to a mean 212 days per year. It's difficult to make firm conclusions based on this study, given the unusual outcome measure of number of days per year taking a psychiatric medication. The authors present a range of possible interpretations in the discussion section of the manuscript for those who are interested.

Study 14: Green, A. E., DeChants, J. P., Price, M. N., & Davis, C. K. (2021). Association of gender-affirming hormone therapy with depression, thoughts of suicide, and attempted suicide among transgender and nonbinary youth. Journal of Adolescent Health.

This study was conducted by researchers from The Trevor Project. They recruited 5,753 transgender adolescents who said they wanted gender-affirming hormone treatment (estrogen or testosterone). Of these, 1,216 had accessed gender-affirming hormones treatment. To focus on the results for only participants who were under 18: After adjusting for potential confounding variables, access to gender-affirming hormones was associated with lower odds of recent depression and suicide attempts when compared to those who desired but did not access gender-affirming hormones.

Study 15: Turban, J. L., King, D., Kobe, J., Reisner, S. L., & Keuroghlian, A. S. (2022). Access to gender-affirming hormones during adolescence and mental health outcomes among transgender adults. PLoS One, 17(1), e0261039.

This study was also conducted by me and other researchers at Harvard Medical School. We examined 21,598 adults who reported ever desiring gender-affirming hormones (estrogen or testosterone). Of these, 481 accessed gender-affirming hormones during adolescence, 12,257 accessed gender-affirming hormones as adults, and 8,860 were never able to access gender-affirming hormones. We found that regardless of age of initiation, accessing gender-affirming hormones was associated with lower odds of past-year suicidal ideation and past year severe psychological distress. We also found that access to gender-affirming hormones during adolescence was associated with a lower odds of these same adverse mental health outcomes when compared to not accessing gender-affirming hormones until adulthood. Because the study was cross-sectional, we created a variable for people who had suicidal ideation in the past but did not have it in the past year (a proxy for mental health improving over time). We found that people who accessed gender-affirming hormones were more likely to meet this criterion than people who desired but did not access gender-affirming hormones, arguing against reverse causation (a common problem with cross-sectional studies).

Study 16: Tordoff, D. M., Wanta, J. W., Collin, A., Stephney, C., Inwards-Breland, D. J., Ahrens, K. (2022) Mental Health Outcomes in Transgender and Nonbinary Youths Receiving Gender-Affirming Care. JAMA Network Open, 5(2), e220978.

This study was a prospective cohort study from Seattle Children's Gender Clinic. The researchers followed 104 transgender and non-binary youth who were receiving gender-affirming medical treatment. After adjusting for temporal trends and potential confounders, they found lower odds of depression and suicidality among young people who had started gender-affirming medical care, when compared to those who did not.

No Randomized Controlled Trials

One will notice that there have not been any randomized controlled trials. There is a general consensus in the field that such a trial would be unethical given the body of literature we have so far indicating that those in the control group would be likely to suffer adverse mental health outcomes compared to those randomized to the treatment groups. For this reason, it appears that no institutional review board would approve a randomized controlled trial at this time, under the principle of "equipoise" to which some bioethicists refer.

In summary, there have been, to my knowledge, 16 studies to date studying the impact of gender-affirming medical care for transgender adolescents. Taken together, the body of research indicates that these interventions result in favorable mental health outcomes. I will continue to update this post as new studies become available. Please feel free to contact me if you are aware of any new studies I have not yet included.

De Vries, A. L., Steensma, T. D., Doreleijers, T. A., & Cohen‐Kettenis, P. T. (2011). Puberty suppression in adolescents with gender identity disorder: A prospective follow‐up study. The Journal of Sexual Medicine, 8(8), 2276-2283.

De Vries, A. L., McGuire, J. K., Steensma, T. D., Wagenaar, E. C., Doreleijers, T. A., & Cohen-Kettenis, P. T. (2014). Young adult psychological outcome after puberty suppression and gender reassignment. Pediatrics, 134(4), 696-704.

Costa, R., Dunsford, M., Skagerberg, E., Holt, V., Carmichael, P., & Colizzi, M. (2015). Psychological support, puberty suppression, and psychosocial functioning in adolescents with gender dysphoria. The Journal of Sexual Medicine, 12(11), 2206-2214.

Allen, L. R., Watson, L. B., Egan, A. M., & Moser, C. N. (2019). Well-being and suicidality among transgender youth after gender-affirming hormones. Clinical Practice in Pediatric Psychology, 7(3), 302.

Kaltiala, R., Heino, E., Työläjärvi, M., & Suomalainen, L. (2020). Adolescent development and psychosocial functioning after starting cross-sex hormones for gender dysphoria. Nordic Journal of Psychiatry, 74(3), 213-219.

de Lara, D. L., Rodríguez, O. P., Flores, I. C., Masa, J. L. P., Campos-Muñoz, L., Hernández, M. C., & Amador, J. T. R. (2020). Psychosocial assessment in transgender adolescents. Anales de Pediatría (English Edition), 93(1), 41-48.

van der Miesen, A. I., Steensma, T. D., de Vries, A. L., Bos, H., & Popma, A. (2020). Psychological functioning in transgender adolescents before and after gender-affirmative care compared with cisgender general population peers. Journal of Adolescent Health, 66(6), 699-704.

Achille, C., Taggart, T., Eaton, N. R., Osipoff, J., Tafuri, K., Lane, A., & Wilson, T. A. (2020). Longitudinal impact of gender-affirming endocrine intervention on the mental health and well-being of transgender youths: preliminary results. International Journal of Pediatric Endocrinology, 2020(1), 1-5.

Kuper, L. E., Stewart, S., Preston, S., Lau, M., & Lopez, X. (2020). Body dissatisfaction and mental health outcomes of youth on gender-affirming hormone therapy. Pediatrics, 145(4).

Turban, J. L., King, D., Carswell, J. M., & Keuroghlian, A. S. (2020). Pubertal suppression for transgender youth and risk of suicidal ideation. Pediatrics, 145(2).

Carmichael, P., Butler, G., Masic, U., Cole, T. J., De Stavola, B. L., Davidson, S., ... & Viner, R. M. (2021). Short-term outcomes of pubertal suppression in a selected cohort of 12 to 15 year old young people with persistent gender dysphoria in the UK. PLoS One, 16(2), e0243894.

Grannis, C., Leibowitz, S. F., Gahn, S., Nahata, L., Morningstar, M., Mattson, W. I., ... & Nelson, E. E. (2021). Testosterone treatment, internalizing symptoms, and body image dissatisfaction in transgender boys. Psychoneuroendocrinology, 132, 105358.

Hisle-Gorman, E., Schvey, N. A., Adirim, T. A., Rayne, A. K., Susi, A., Roberts, T. A., & Klein, D. A. (2021). Mental healthcare utilization of transgender youth before and after affirming treatment. The Journal of Sexual Medicine, 18(8), 1444-1454.

Green, A. E., DeChants, J. P., Price, M. N., & Davis, C. K. (2021). Association of gender-affirming hormone therapy with depression, thoughts of suicide, and attempted suicide among transgender and nonbinary youth. Journal of Adolescent Health.

Turban, J. L., King, D., Kobe, J., Reisner, S. L., & Keuroghlian, A. S. (2022). Access to gender-affirming hormones during adolescence and mental health outcomes among transgender adults. PLoS One, 17(1), e0261039.

Tordoff, D. M., Wanta, J. W., Collin, A., Stephney, C., Inwards-Breland, D. J., Ahrens, K. (2022) Mental Health Outcomes in Transgender and Nonbinary Youths Receiving Gender-Affirming Care. JAMA Network Open, 5(2), e220978.

Jack Turban MD MHS is a writer and fellow in child and adolescent psychiatry at Stanford University School of Medicine, where he researches the mental health of transgender and gender diverse youth.

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What does the scholarly research say about the effect of gender transition on transgender well-being?

We conducted a systematic literature review of all peer-reviewed articles published in English between 1991 and June 2017 that assess the effect of gender transition on transgender well-being. We identified 55 studies that consist of primary research on this topic, of which 51 (93%) found that gender transition improves the overall well-being of transgender people, while 4 (7%) report mixed or null findings. We found no studies concluding that gender transition causes overall harm. As an added resource, we separately include 17 additional studies that consist of literature reviews and practitioner guidelines.

Bottom Line

This search found a robust international consensus in the peer-reviewed literature that gender transition, including medical treatments such as hormone therapy and surgeries, improves the overall well-being of transgender individuals. The literature also indicates that greater availability of medical and social support for gender transition contributes to better quality of life for those who identify as transgender.

Below are the 8 findings of our review, and links to the 72 studies on which they are based. Click here to view our methodology . Click here for a printer-friendly one-pager of this research analysis .

Suggested Citation : What We Know Project, Cornell University, “What Does the Scholarly Research Say about the Effect of Gender Transition on Transgender Well-Being?” (online literature review), 2018.

Research Findings

1. The scholarly literature makes clear that gender transition is effective in treating gender dysphoria and can significantly improve the well-being of transgender individuals.

2. Among the positive outcomes of gender transition and related medical treatments for transgender individuals are improved quality of life, greater relationship satisfaction, higher self-esteem and confidence, and reductions in anxiety, depression, suicidality, and substance use.

3. The positive impact of gender transition on transgender well-being has grown considerably in recent years, as both surgical techniques and social support have improved.

4. Regrets following gender transition are extremely rare and have become even rarer as both surgical techniques and social support have improved. Pooling data from numerous studies demonstrates a regret rate ranging from .3 percent to 3.8 percent. Regrets are most likely to result from a lack of social support after transition or poor surgical outcomes using older techniques.

5. Factors that are predictive of success in the treatment of gender dysphoria include adequate preparation and mental health support prior to treatment, proper follow-up care from knowledgeable providers, consistent family and social support, and high-quality surgical outcomes (when surgery is involved).

6. Transgender individuals, particularly those who cannot access treatment for gender dysphoria or who encounter unsupportive social environments, are more likely than the general population to experience health challenges such as depression, anxiety, suicidality and minority stress. While gender transition can mitigate these challenges, the health and well-being of transgender people can be harmed by stigmatizing and discriminatory treatment.

7. An inherent limitation in the field of transgender health research is that it is difficult to conduct prospective studies or randomized control trials of treatments for gender dysphoria because of the individualized nature of treatment, the varying and unequal circumstances of population members, the small size of the known transgender population, and the ethical issues involved in withholding an effective treatment from those who need it.

8. Transgender outcomes research is still evolving and has been limited by the historical stigma against conducting research in this field. More research is needed to adequately characterize and address the needs of the transgender population.

Below are 51 studies that found that gender transition improves the well-being of transgender people. Click here to jump to 4 studies that contain mixed or null findings on the effect of gender transition on transgender well-being. Click here to jump to 17 studies that consist of literature reviews or guidelines that help advance knowledge about the effect of gender transition on transgender well-being.

Ainsworth and spiegel, 2010.

Ainsworth, T., & Spiegel, J. (2010). Quality of life of individuals with and without facial feminization surgery or gender reassignment surgery. Quality of Life Research , 19 (7), 1019-1024.

Objectives: To determine the self-reported quality of life of male-to-female (MTF) transgendered individuals and how this quality of life is influenced by facial feminization and gender reassignment surgery. Methods: Facial Feminization Surgery outcomes evaluation survey and the SF-36v2 quality of life survey were administered to male-to-female transgender individuals via the Internet and on paper. A total of 247 MTF participants were enrolled in the study. Results: Mental health-related quality of life was statistically diminished (P < 0.05) in transgendered women without surgical intervention compared to the general female population and transwomen who had gender reassignment surgery (GRS), facial feminization surgery (FFS), or both. There was no statistically significant difference in the mental health-related quality of life among transgendered women who had GRS, FFS, or both. Participants who had FFS scored statistically higher (P < 0.01) than those who did not in the FFS outcomes evaluation. Conclusions: Transwomen have diminished mental health-related quality of life compared with the general female population. However, surgical treatments (e.g. FFS, GRS, or both) are associated with improved mental health-related quality of life.

Bailey, Ellis, & McNeil, 2014

Bailey, L., Ellis, S. J., & McNeil, J. (2014). Suicide risk in the UK trans population and the role of gender transition in decreasing suicidal ideation and suicide attempt. The Mental Health Review , 19 (4), 209-220.

Purpose: The purpose of this paper is to present findings from the Trans Mental Health Study (McNeil et al., 2012) – the largest survey of the UK trans population to date and the first to explore trans mental health and well-being within a UK context. Findings around suicidal ideation and suicide attempt are presented and the impact of gender dysphoria, minority stress and medical delay, in particular, are highlighted. Design/methodology/approach: This represents a narrative analysis of qualitative sections of a survey that utilised both open and closed questions. The study drew on a non-random sample (n 1⁄4 889), obtained via a range of UK-based support organisations and services. Findings: The study revealed high rates of suicidal ideation (84 per cent lifetime prevalence) and attempted suicide (48 per cent lifetime prevalence) within this sample. A supportive environment for social transition and timely access to gender reassignment, for those who required it, emerged as key protective factors. Subsequently, gender dysphoria, confusion/denial about gender, fears around transitioning, gender reassignment treatment delays and refusals, and social stigma increased suicide risk within this sample. Research limitations/implications: Due to the limitations of undertaking research with this population, the research is not demographically representative. Practical implications: The study found that trans people are most at risk prior to social and/or medical transition and that, in many cases, trans people who require access to hormones and surgery can be left unsupported for dangerously long periods of time. The paper highlights the devastating impact that delaying or denying gender reassignment treatment can have and urges commissioners and practitioners to prioritise timely intervention and support. Originality/value: The first exploration of suicidal ideation and suicide attempt within the UK trans population revealing key findings pertaining to social and medical transition, crucial for policy makers, commissioners and practitioners working across gender identity services, mental health services and suicide prevention.

Bar et al., 2016

Bar, M. A., Jarus, T., Wada, M., Rechtman, L., & Noy, E. (2016). Male-to-female transitions: Implications for occupational performance, health, and life satisfaction. The Canadian Journal of Occupational Therapy , 83 (2), 72-82.

Background. People who undergo a gender transition process experience changes in different everyday occupations. These changes may impact their health and life satisfaction. Purpose. This study examined the difference in the occupational performance history scales (occupational identity, competence, and settings) between male-to-female transgender women and cisgender women and the relation of these scales to health and life satisfaction. Method. Twenty-two transgender women and 22 matched cisgender women completed a demographic questionnaire and three reliable measures in this cross-sectional study. Data were analyzed using a two-way analysis of variance and multiple linear regressions. Findings. The results indicate lower performance scores for the transgender women. In addition, occupational settings and group membership (transgender and cisgender groups) were found to be predictors of life satisfaction. Implications. The present study supports the role of occupational therapy in promoting occupational identity and competence of transgender women and giving special attention to their social and physical environment.

Bodlund and Kullgren, 1996

Bodlund, O., & Kullgren, G. (1996). Transsexualism–general outcome and prognostic factors: A five-year follow-up study of nineteen transsexuals in the process of changing sex. Archives of Sexual Behavior , 25 (3), 303-316.

Nineteen transsexuals, approved for sex reassignement, were followed-up after 5 years. Outcome was evaluated as changes in seven areas of social, psychological, and psychiatric functioning. At baseline the patients were evaluated according to axis I, II, V (DSM-III-R), SCID screen, SASB (Structural Analysis of Social Behavior), and DMT (Defense Mechanism Test). At follow-up all but 1 were treated with contrary sex hormones, 12 had completed sex reassignment surgery, and 3 females were waiting for phalloplasty. One male transsexual regretted the decision to change sex and had quit the process. Two transsexuals had still not had any surgery due to older age or ambivalence. Overall, 68% (n = 13) had improved in at least two areas of functioning. In 3 cases (16%) outcome were judged as unsatisfactory and one of those regarded sex change as a failure. Another 3 patients were mainly unchanged after 5 years. Female transsexuals had a slightly better outcome, especially concerning establishing and maintaining partnerships and improvement in socio-economic status compared to male transsexuals. Baseline factors associated with negative outcome (unchanged or worsened) were presence of a personality disorder and high number of fulfilled axis II criteria. SCID screen assessments had high prognostic power. Negative self-image, according to SASB, predicted a negative outcome, whereas DMT variables were not correlated to outcome.

Bouman et al., 2016

Bouman, W. P., Claes, L., Marshall, E., Pinner, G. T., Longworth, J., et al. (2016). Sociodemographic variables, clinical features, and the role of preassessment cross-sex hormones in older trans people. The Journal of Sexual Medicine , 13 (4), 711-719.

Introduction: As referrals to gender identity clinics have increased dramatically over the last few years, no studies focusing on older trans people seeking treatment are available. Aims: The aim of this study was to investigate the sociodemographic and clinical characteristics of older trans people attending a national service and to investigate the influence of cross-sex hormones (CHT) on psychopathology. Methods: Individuals over the age of 50 years old referred to a national gender identity clinic during a 30-month period were invited to complete a battery of questionnaires to measure psychopathology and clinical characteristics. Individuals on cross-sex hormones prior to the assessment were compared with those not on treatment for different variables measuring psychopathology. Main Outcome Measures: Sociodemographic and clinical variables and measures of depression and anxiety (Hospital Anxiety and Depression Scale), self-esteem (Rosenberg Self-Esteem Scale), victimization (Experiences of Transphobia Scale), social support (Multidimensional Scale of Perceived Social Support), interpersonal functioning (Inventory of Interpersonal Problems), and nonsuicidal self-injury (Self-Injury Questionnaire). Results: The sex ratio of trans females aged 50 years and older compared to trans males was 23.7:1. Trans males were removed for the analysis due to their small number (n = 3). Participants included 71 trans females over the age of 50, of whom the vast majority were white, employed or retired, and divorced and had children. Trans females on CHT who came out as trans and transitioned at an earlier age were significantly less anxious, reported higher levels of self-esteem, and presented with fewer socialization problems. When controlling for socialization problems, differences in levels of anxiety but not self-esteem remained. Conclusion: The use of cross-sex hormones prior to seeking treatment is widespread among older trans females and appears to be associated with psychological benefits. Existing barriers to access CHT for older trans people may need to be re-examined.

Boza and Nicholson, 2014

Boza, C., & Nicholson Perry, K. (2014). Gender-related victimization, perceived social support, and predictors of depression among transgender Australians. International Journal Of Transgenderism , 15 (1), 35-52.

This study examined mental health outcomes, gender-related victimization, perceived social support, and predictors of depression among 243 transgender Australians (n= 83 assigned female at birth, n= 160 assigned male at birth). Overall, 69% reported at least 1 instance of victimization, 59% endorsed depressive symptoms, and 44% reported a previous suicide attempt. Social support emerged as the most significant predictor of depressive symptoms (p>.05), whereby persons endorsing higher levels of overall perceived social support tended to endorse lower levels of depressive symptoms. Second to social support, persons who endorsed having had some form of gender affirmative surgery were significantly more likely to present with lower symptoms of depression. Contrary to expectations, victimization did not reach significance as an independent risk factor of depression (p=.053). The pervasiveness of victimization, depression, and attempted suicide represents a major health concern and highlights the need to facilitate culturally sensitive health care provision.

Budge et al., 2013

Budge, S. L., Katz-Wise, S. L., Tebbe, E. N., Howard, K. A. S., Schneider, C. L., et al. (2013). Transgender emotional and coping processes: Facilitative and avoidant coping throughout gender transitioning. The Counseling Psychologist , 41 (4), 601-647.

Eighteen transgender-identified individuals participated in semi-structured interviews regarding emotional and coping processes throughout their gender transition. The authors used grounded theory to conceptualize and analyze the data. There were three distinct phases through which the participants described emotional and coping experiences: (a) pretransition, (b) during the transition, and (c) posttransition. Five separate themes emerged, including descriptions of coping mechanisms, emotional hardship, lack of support, positive social support, and affirmative emotional experiences. The authors developed a model to describe the role of coping mechanisms and support experienced throughout the transition process. As participants continued through their transitions, emotional hardships lessened and they used facilitative coping mechanisms that in turn led to affirmative emotional experiences. The results of this study are indicative of the importance of guiding transgender individuals through facilitative coping experiences and providing social support throughout the transition process. Implications for counselors and for future research are discussed.

Cardoso da Silva et al., 2016

Cardoso da Silva, D., Schwarz, K., Fontanari, A.M.V., Costa, A.B., Massuda, R., et al. (2016). WHOQOL-100 Before and after sex reassignment surgery in Brazilian male-to-female transsexual individuals. Journal of Sexual Medicine , 13 (6), 988-993.

Introduction: The 100-item World Health Organization Quality of Life Assessment (WHOQOL-100) evaluates quality of life as a subjective and multidimensional construct. Currently, particularly in Brazil, there are controversies concerning quality of life after sex reassignment surgery (SRS). Aim: To assess the impact of surgical interventions on quality of life of 47 Brazilian male-to-female transsexual individuals using the WHOQOL-100. Methods: This was a prospective cohort study using the WHOQOL-100 and sociodemographic questions for individuals diagnosed with gender identity disorder according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The protocol was used when a transsexual person entered the ambulatory clinic and at least 12 months after SRS. Main Outcome Measures: Initially, improvement or worsening of quality of life was assessed using 6 domains and 24 facets. Subsequently, quality of life was assessed for individuals who underwent new surgical interventions and those who did not undergo these procedures 1 year after SRS. Results: The participants showed significant improvement after SRS in domains II (psychological) and IV (social relationships) of the WHOQOL-100. In contrast, domains I (physical health) and III (level of independence) were significantly worse after SRS. Individuals who underwent additional surgery had a decrease in quality of life reflected in domains II and IV. During statistical analysis, all results were controlled for variations in demographic characteristics, without significant results. Conclusion: The WHOQOL-100 is an important instrument to evaluate the quality of life of male-to-female transsexuals during different stages of treatment. SRS promotes the improvement of psychological aspects and social relationships. However, even 1 year after SRS, male-to-female transsexuals continue to report problems in physical health and difficulty in recovering their independence.

(Due to a citation error, this study was initially listed twice.)

Castellano et al., 2015

Castellano, E., Crespi, C., Dell’Aquila, R., Rosato, C., Catalano, V., et al. (2015). Quality of life and hormones after sex reassignment surgery.  Journal of Endocrinological Investigation , 38 (12), 1373-1381.

Background: Transpeople often look for sex reassignment surgery (SRS) to improve their quality of life (QoL). The hormonal therapy has many positive effects before and after SRS. There are no studies about correlation between hormonal status and QoL after SRS. Aim: To gather information on QoL, quality of sexual life and body image in transpeople at least 2 years after SRS, to compare these results with a control group and to evaluate the relations between the chosen items and hormonal status. Subjects and methods: Data from 60 transsexuals and from 60 healthy matched controls were collected. Testosterone, estradiol, LH and World Health Organization Quality of Life (WHOQOL-100) self-reported questionnaire were evaluated. Student’s t test was applied to compare transsexuals and controls. Multiple regression model was applied to evaluate WHOQOL’s chosen items and LH. Results: The QoL and the quality of body image scores in transpeople were not statistically different from the matched control groups’ ones. In the sexual life subscale, transwomen’s scores were similar to biological women’s ones, whereas transmen’s scores were statistically lower than biological men’s ones (P = 0.003). The quality of sexual life scored statistically lower in transmen than in transwomen (P = 0.048). A significant inverse relationship between LH and body image and between LH and quality of sexual life was found. Conclusions: This study highlights general satisfaction after SRS. In particular, transpeople’s QoL turns out to be similar to Italian matched controls. LH resulted inversely correlated to body image and sexual life scores.

Colizzi, Costa, & Todarello, 2014

Colizzi, M., Costa, R. & Todarello, O. (2014). Transsexual patients’ psychiatric comorbidity and positive effect of cross-sex hormonal treatment on mental health: Results from a longitudinal study.  Psychoneuroendocrinology , 39 , 65-73.

The aim of the present study was to evaluate the presence of psychiatric diseases/symptoms in transsexual patients and to compare psychiatric distress related to the hormonal intervention in a one year follow-up assessment. We investigated 118 patients before starting the hormonal therapy and after about 12 months. We used the SCID-I to determine major mental disorders and functional impairment. We used the Zung Self-Rating Anxiety Scale (SAS) and the Zung Self-Rating Depression Scale (SDS) for evaluating self-reported anxiety and depression. We used the Symptom Checklist 90-R (SCL-90-R) for assessing self-reported global psychological symptoms. Seventeen patients (14%) had a DSM-IV-TR axis I psychiatric comorbidity. At enrollment the mean SAS score was above the normal range. The mean SDS and SCL-90-R scores were on the normal range except for SCL-90-R anxiety subscale. When treated, patients reported lower SAS, SDS and SCL-90-R scores, with statistically significant differences. Psychiatric distress and functional impairment were present in a significantly higher percentage of patients before starting the hormonal treatment than after 12 months (50% vs. 17% for anxiety; 42% vs. 23% for depression; 24% vs. 11% for psychological symptoms; 23% vs. 10% for functional impairment). The results revealed that the majority of transsexual patients have no psychiatric comorbidity, suggesting that transsexualism is not necessarily associated with severe comorbid psychiatric findings. The condition, however, seemed to be associated with subthreshold anxiety/depression, psychological symptoms and functional impairment. Moreover, treated patients reported less psychiatric distress. Therefore, hormonal treatment seemed to have a positive effect on transsexual patients’ mental health.

Colizzi et al., 2013

Colizzi. M., Costa, R., Pace, V., & Todarello, O. (2013). Hormonal treatment reduces psychobiological distress in gender identity disorder, independently of the attachment style. The Journal of Sexual Medicine , 10 (12), 3049–3058.

Introduction: Gender identity disorder may be a stressful situation. Hormonal treatment seemed to improve the general health as it reduces psychological and social distress. The attachment style seemed to regulate distress in insecure individuals as they are more exposed to hypothalamic–pituitary–adrenal system dysregulation and subjective stress. Aim: The objectives of the study were to evaluate the presence of psychobiological distress and insecure attachment in transsexuals and to study their stress levels with reference to the hormonal treatment and the attachment pattern. Methods: We investigated 70 transsexual patients. We measured the cortisol levels and the perceived stress before starting the hormonal therapy and after about 12 months. We studied the representation of attachment in transsexuals by a backward investigation in the relations between them and their caregivers. Main Outcome Measures: We used blood samples for assessing cortisol awakening response (CAR); we used the Perceived Stress Scale for evaluating self‐reported perceived stress and the Adult Attachment Interview to determine attachment styles. Results: At enrollment, transsexuals reported elevated CAR; their values were out of normal. They expressed higher perceived stress and more attachment insecurity, with respect to normative sample data. When treated with hormone therapy, transsexuals reported significantly lower CAR (P < 0.001), falling within the normal range for cortisol levels. Treated transsexuals showed also lower perceived stress (P < 0.001), with levels similar to normative samples. The insecure attachment styles were associated with higher CAR and perceived stress in untreated transsexuals (P < 0.01). Treated transsexuals did not expressed significant differences in CAR and perceived stress by attachment. Conclusion: Our results suggested that untreated patients suffer from a higher degree of stress and that attachment insecurity negatively impacts the stress management. Initiating the hormonal treatment seemed to have a positive effect in reducing stress levels, whatever the attachment style may be.

Colton-Meier et al., 2011

Colton-Meier, S. L., Fitzgerald, K. M., Pardo, S. T., & Babcock, J. (2011). The effects of hormonal gender affirmation treatment on mental health in female-to-male transsexuals. Journal of Gay & Lesbian Mental Health , 15 (3), 281-299.

Hormonal interventions are an often-sought option for transgender individuals seeking to medically transition to an authentic gender. Current literature stresses that the effects and associated risks of hormone regimens should be monitored and well understood by health care providers (Feldman & Bockting, 2003). However, the positive psychological effects following hormone replacement therapy as a gender affirming treatment have not been adequately researched. This study examined the relationship of hormone replacement therapy, specifically testosterone, with various mental health outcomes in an Internet sample of more than 400 self-identified female-to-male transsexuals. Results of the study indicate that female-to-male transsexuals who receive testosterone have lower levels of depression, anxiety, and stress, and higher levels of social support and health related quality of life. Testosterone use was not related to problems with drugs, alcohol, or suicidality. Overall findings provide clear evidence that HRT is associated with improved mental health outcomes in female-to-male transsexuals.

Costantino et al., 2013

Costantino, A., Cerpolini, S., Alvisi, S., Morselli, P. G., Venturoli, S., & Meriggiola, M. C. (2013). A prospective study on sexual function and mood in female-to-male transsexuals during testosterone administration and after sex reassignment surgery. Journal of Sex & Marital Therapy , 39 (4), 321-335.

Testosterone administration in female-to-male transsexual subjects aims to develop and maintain the characteristics of the desired sex. Very little data exists on its effects on sexuality of female-to-male transsexuals. The aim of this study was to evaluate sexual function and mood of female-to-male transsexuals from their first visit, throughout testosterone administration and after sex reassignment surgery. Participants were 50 female-to-male transsexual subjects who completed questionnaires assessing sexual parameters and mood. The authors measured reproductive hormones and hematological parameters. The results suggest a positive effect of testosterone treatment on sexual function and mood in female-to-male transsexual subjects.

Davis and Meier, 2014

Davis, S. A. & Meier, S. C. (2014). Effects of testosterone treatment and chest reconstruction surgery on mental health and sexuality in female-to-male transgender people. International Journal of Sexual Health , 26 (2), 113-128.

Objectives: This study examined the effects of testosterone treatment with or without chest reconstruction surgery (CRS) on mental health in female-to-male transgender people (FTMs). Methods: More than 200 FTMs completed a written survey including quantitative scales to measure symptoms of anxiety and depression, feelings of anger, and body dissatisfaction, as well as qualitative questions assessing shifts in sexuality after the initiation of testosterone. Fifty-seven percent of participants were taking testosterone and 40% had undergone CRS. Results: Cross-sectional analysis using a between-subjects multivariate analysis of variance showed that participants who were receiving testosterone endorsed fewer symptoms of anxiety and depression as well as less anger than the untreated group. Participants who had CRS in addition to testosterone reported less body dissatisfaction than both the testosterone-only or the untreated groups. Furthermore, participants who were injecting testosterone on a weekly basis showed significantly less anger compared with those injecting every other week. In qualitative reports, more than 50% of participants described increased sexual attraction to nontransgender men after taking testosterone. Conclusions: Results indicate that testosterone treatment in FTMs is associated with a positive effect on mental health on measures of depression, anxiety, and anger, while CRS appears to be more important for the alleviation of body dissatisfaction. The findings have particular relevance for counselors and health care providers serving FTM and gender-variant people considering medical gender transition.

De Cuypere et al., 2006

De Cuypere, G., Elaut, E., Heylens, G., Maele, G. V., Selvaggi, G., et al. (2006). Long-term follow-up: Psychosocial outcome of Belgian transsexuals after sex reassignment surgery. Sexologies , 15 (2), 126-133.

Background: To establish the benefit of sex reassignment surgery (SRS) for persons with a gender identity disorder, follow-up studies comprising large numbers of operated transsexuals are still needed. Aims: The authors wanted to assess how the transsexuals who had been treated by the Ghent multidisciplinary gender team since 1985, were functioning psychologically, socially and professionally after a longer period. They also explored some prognostic factors with a view to refining the procedure. Method: From 107 Dutch-speaking transsexuals who had undergone SRS between 1986 and 2001, 62 (35 male-to-females and 27 female-to-males) completed various questionnaires and were personally interviewed by researchers, who had not been involved in the subjects’ initial assessment or treatment. Results: On the GAF (DSM-IV) scale the female-to-male transsexuals scored significantly higher than the male-to-females (85.2 versus 76.2). While no difference in psychological functioning (SCL-90) was observed between the study group and a normal population, subjects with a pre-existing psychopathology were found to have retained more psychological symptoms. The subjects proclaimed an overall positive change in their family and social life. None of them showed any regrets about the SRS. A homosexual orientation, a younger age when applying for SRS, and an attractive physical appearance were positive prognostic factors. Conclusion: While sex reassignment treatment is an effective therapy for transsexuals, also in the long term, the postoperative transsexual remains a fragile person in some respects.

Dhejne et al., 2014

Dhejne, C., Öberg, K., Arver, S., & Landén, M. (2014). An analysis of all applications for sex reassignment surgery in sweden, 1960-2010: Prevalence, incidence, and regrets. Archives of Sexual Behavior , 43 (8), 1535-1545.

Incidence and prevalence of applications in Sweden for legal and surgical sex reassignment were examined over a 50-year period (1960-2010), including the legal and surgical reversal applications. A total of 767 people (289 natal females and 478 natal males) applied for legal and surgical sex reassignment. Out of these, 89 % (252 female-to-males [FM] and 429 male-to-females [MF]) received a new legal gender and underwent sex reassignment surgery (SRS). A total of 25 individuals (7 natal females and 18 natal males), equaling 3.3 %, were denied a new legal gender and SRS. The remaining withdrew their application, were on a waiting list for surgery, or were granted partial treatment. The incidence of applications was calculated and stratified over four periods between 1972 and 2010. The incidence increased significantly from 0.16 to 0.42/100,000/year (FM) and from 0.23 to 0.73/100,000/year (MF). The most pronounced increase occurred after 2000. The proportion of FM individuals 30 years or older at the time of application remained stable around 30 %. In contrast, the proportion of MF individuals 30 years or older increased from 37 % in the first decade to 60 % in the latter three decades. The point prevalence at December 2010 for individuals who applied for a new legal gender was for FM 1:13,120 and for MF 1:7,750. The FM:MF sex ratio fluctuated but was 1:1.66 for the whole study period. There were 15 (5 MF and 10 MF) regret applications corresponding to a 2.2 % regret rate for both sexes. There was a significant decline of regrets over the time period.

Eldh, Berg, & Gustafsson, 1997

Eldh, J., Berg, A., Gustafsson, M. (1997). Long-term follow up after sex reassignment surgery. Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery , 27 (1), 39-45.

A long-term follow up of 136 patients operated on for sex reassignment was done to evaluate the surgical outcome. Social and psychological adjustments were also investigated by a questionnaire in 90 of these 136 patients. Optimal results of the operation are essential for a successful outcome. Personal and social instability before operation, unsuitable body build, and age over 30 years at operation correlated with unsatisfactory results. Adequate family and social support is important for postoperative functioning. Sex reassignment had no influence on the person’s ability to work.

Fisher et al., 2014

Fisher, A. D., Castellini, G., Bandini, E., Casale, H., Fanni, E., et al. (2014). Cross‐sex hormonal treatment and body uneasiness in individuals with gender dysphoria. The Journal of Sexual Medicine , 11 (3), 709–719.

Introduction: Cross‐sex hormonal treatment (CHT) used for gender dysphoria (GD) could by itself affect well‐being without the use of genital surgery; however, to date, there is a paucity of studies investigating the effects of CHT alone. Aims: This study aimed to assess differences in body uneasiness and psychiatric symptoms between GD clients taking CHT and those not taking hormones (no CHT). A second aim was to assess whether length of CHT treatment and daily dose provided an explanation for levels of body uneasiness and psychiatric symptoms. Methods: A consecutive series of 125 subjects meeting the criteria for GD who not had genital reassignment surgery were considered. Main Outcome Measures: Subjects were asked to complete the Body Uneasiness Test (BUT) to explore different areas of body‐related psychopathology and the Symptom Checklist‐90 Revised (SCL‐90‐R) to measure psychological state. In addition, data on daily hormone dose and length of hormonal treatment (androgens, estrogens, and/or antiandrogens) were collected through an analysis of medical records. Results: Among the male‐to‐female (MtF) individuals, those using CHT reported less body uneasiness compared with individuals in the no‐CHT group. No significant differences were observed between CHT and no‐CHT groups in the female‐to‐male (FtM) sample. Also, no significant differences in SCL score were observed with regard to gender (MtF vs. FtM), hormone treatment (CHT vs. no‐CHT), or the interaction of these two variables. Moreover, a two‐step hierarchical regression showed that cumulative dose of estradiol (daily dose of estradiol times days of treatment) and cumulative dose of androgen blockers (daily dose of androgen blockers times days of treatment) predicted BUT score even after controlling for age, gender role, cosmetic surgery, and BMI. Conclusions: The differences observed between MtF and FtM individuals suggest that body‐related uneasiness associated with GD may be effectively diminished with the administration of CHT even without the use of genital surgery for MtF clients. A discussion is provided on the importance of controlling both length and daily dose of treatment for the most effective impact on body uneasiness.

Glynn et al., 2016

Glynn, T. R., Gamarel, K. E., Kahler, C. W., Iwamoto, M., Operario, D., & Nemoto, T. (2016). The role of gender affirmation in psychological well-being among transgender women. Psychology Of Sexual Orientation And Gender Diversity , 3 (3), 336-344.

High prevalence of psychological distress, including greater depression, lower self-esteem, and suicidal ideation, has been documented across numerous samples of transgender women and has been attributed to high rates of discrimination and violence. According to the gender affirmation framework (Sevelius, 2013), access to sources of gender-affirmative support can offset such negative psychological effects of social oppression. However, critical questions remain unanswered in regards to how and which aspects of gender affirmation are related to psychological well-being. The aims of this study were to investigate the associations among 3 discrete areas of gender affirmation (psychological, medical, and social) and participants’ reports of psychological well-being. A community sample of 573 transgender women with a history of sex work completed a 1-time self-report survey that assessed demographic characteristics, gender affirmation, and mental health outcomes. In multivariate models, we found that social, psychological, and medical gender affirmation were significant predictors of lower depression and higher self-esteem whereas no domains of affirmation were significantly associated with suicidal ideation. Findings support the need for accessible and affordable transitioning resources for transgender women to promote better quality of life among an already vulnerable population. However, transgender individuals should not be portrayed simplistically as objects of vulnerability, and research identifying mechanisms to promote wellness and thriving is necessary for future intervention development. As the gender affirmation framework posits, the personal experience of feeling affirmed as a transgender person results from individuals’ subjective perceptions of need along multiple dimensions of gender affirmation. Thus, personalized assessment of gender affirmation may be a useful component of counseling and service provision for transgender women.

Gomez-Gil et al., 2012

Gomez-Gil, E., Zubiaurre-Elorz, L., Esteva, I., Guillamon, A., Godas, T., Cruz Almaraz, M., Halperin, I., Salamero, M. (2012). Hormone-treated transsexuals report less social distress, anxiety and depression. Psychoneuroendocrinology , 37 (5), 662-670.

Introduction: The aim of the present study was to evaluate the presence of symptoms of current social distress, anxiety and depression in transsexuals. Methods: We investigated a group of 187 transsexual patients attending a gender identity unit; 120 had undergone hormonal sex-reassignment (SR) treatment and 67 had not. We used the Social Anxiety and Distress Scale (SADS) for assessing social anxiety and the Hospital Anxiety and Depression Scale (HADS) for evaluating current depression and anxiety. Results: The mean SADS and HADS scores were in the normal range except for the HAD-Anxiety subscale (HAD-A) on the non-treated transsexual group. SADS, HAD-A, and HAD-Depression (HAD-D) mean scores were significantly higher among patients who had not begun cross-sex hormonal treatment compared with patients in hormonal treatment (F = 4.362, p = .038; F = 14.589, p = .001; F = 9.523, p = .002 respectively). Similarly, current symptoms of anxiety and depression were present in a significantly higher percentage of untreated patients than in treated patients (61% vs. 33% and 31% vs. 8% respectively). Conclusions: The results suggest that most transsexual patients attending a gender identity unit reported subclinical levels of social distress, anxiety, and depression. Moreover, patients under cross-sex hormonal treatment displayed a lower prevalence of these symptoms than patients who had not initiated hormonal therapy. Although the findings do not conclusively demonstrate a direct positive effect of hormone treatment in transsexuals, initiating this treatment may be associated with better mental health of these patients.

Gomez-Gil et al., 2014

Gómez-Gil, E., Zubiaurre-Elorza, L., de Antonio, E. D., Guillamon, A., & Salamero, M. (2014). Determinants of quality of life in Spanish transsexuals attending a gender unit before genital sex reassignment surgery. Quality of Life Research , 23 (2), 669-676.

Purpose: To evaluate the self-reported perceived quality of life (QoL) in transsexuals attending a Spanish gender identity unit before genital sex reassignment surgery, and to identify possible determinants that likely contribute to their QoL. Methods: A sample of 119 male-to-female (MF) and 74 female-to-male (FM) transsexuals were included in the study. The WHOQOL-BREF scale was used to evaluate self-reported QoL. Possible determinants included age, sex, education, employment, partnership status, undergoing cross-sex hormonal therapy, receiving at least one non-genital sex reassignment surgery, and family support (assessed with the family APGAR questionnaire). Results: Mean scores of all QoL domains ranged from 55.44 to 63.51. Linear regression analyses revealed that undergoing cross-sex hormonal treatment, having family support, and having an occupation were associated with a better QoL for all transsexuals. FM transsexuals have higher social domain QoL scores than MF transsexuals. The model accounts for 20.6 % of the variance in the physical, 32.5 % in the psychological, 21.9 % in the social, and 20.1 % in the environment domains, and 22.9 % in the global QoL factor. Conclusions: Cross-sex hormonal treatment, family support, and working or studying are linked to a better self-reported QoL in transsexuals. Healthcare providers should consider these factors when planning interventions to promote the health-related QoL of transsexuals.

Gorin-Lazard et al., 2012

Gorin‐Lazard, A., Baumstarck, K., Boyer, L., Maquigneau, A., Gebleux, S., Penochet, J., Pringuey, D., Albarel, F., Morange, I., Loundou, A., Berbis, J., Auquier, P., Lançon, C. and Bonierbale, M. (2012). Is hormonal therapy associated with better quality of life in transsexuals? A cross‐sectional study. The Journal of Sexual Medicine , 9 (2), 531–541.

Introduction: Although the impact of sex reassignment surgery on the self‐reported outcomes of transsexuals has been largely described, the data available regarding the impact of hormone therapy on the daily lives of these individuals are scarce. Aims: The objectives of this study were to assess the relationship between hormonal therapy and the self‐reported quality of life (QoL) in transsexuals while taking into account the key confounding factors and to compare the QoL levels between transsexuals who have, vs. those who have not, undergone cross‐sex hormone therapy as well as between transsexuals and the general population (French age‐ and sex‐matched controls). Methods: This study incorporated a cross‐sectional design that was conducted in three psychiatric departments of public university teaching hospitals in France. The inclusion criteria were as follows: 18 years or older, diagnosis of gender identity disorder (302.85) according to the Diagnostic and Statistical Manual, fourth edition text revision (DSM‐IV TR), inclusion in a standardized sex reassignment procedure following the agreement of a multidisciplinary team, and pre‐sex reassignment surgery. Main Outcome Measure. QoL was assessed using the Short Form 36 (SF‐36). Results: The mean age of the total sample was 34.7 years, and the sex ratio was 1:1. Forty‐four (72.1%) of the participants received hormonal therapy. Hormonal therapy and depression were independent predictive factors of the SF‐36 mental composite score. Hormonal therapy was significantly associated with a higher QoL, while depression was significantly associated with a lower QoL. Transsexuals’ QoL, independently of hormonal status, did not differ from the French age‐ and sex‐matched controls except for two subscales of the SF‐36 questionnaire: role physical (lower scores in transsexuals) and general health (lower scores in controls). Conclusion: The present study suggests a positive effect of hormone therapy on transsexuals’ QoL after accounting for confounding factors. These results will be useful for healthcare providers of transgender persons but should be confirmed with larger samples using a prospective study design.

Gorin-Lazard et al., 2013

Gorin-Lazard, A., Baumstarck, K., Boyer, L., Maquigneau, A., Penochet, J. C., et al. (2013). Hormonal therapy is associated with better self-esteem, mood, and quality of life in transsexuals. Journal of Nervous and Mental Disease , 201 (11), 996–1000.

Few studies have assessed the role of cross-sex hormones on psychological outcomes during the period of hormonal therapy preceding sex reassignment surgery in transsexuals. The objective of this study was to assess the relationship between hormonal therapy, self-esteem, depression, quality of life (QoL), and global functioning. This study incorporated a cross-sectional design. The inclusion criteria were diagnosis of gender identity disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) and inclusion in a standardized sex reassignment procedure. The outcome measures were self-esteem (Social Self-Esteem Inventory), mood (Beck Depression Inventory), QoL (Subjective Quality of Life Analysis), and global functioning (Global Assessment of Functioning). Sixty-seven consecutive individuals agreed to participate. Seventy-three percent received hormonal therapy. Hormonal therapy was an independent factor in greater self-esteem, less severe depression symptoms, and greater “psychological-like” dimensions of QoL. These findings should provide pertinent information for health care providers who consider this period as a crucial part of the global sex reassignment procedure.

Hess et al., 2014

Hess, J., Neto, R. R., Panic, L., Rübben, H., & Senf, W. (2014). Satisfaction with male-to-female gender reassignment surgery: Results of a retrospective analysis. Deutsches Ärzteblatt International , 111 (47), 795–801.

Background: The frequency of gender identity disorder is hard to determine; the number of gender reassignment operations and of court proceedings in accordance with the German Law on Transsexuality almost certainly do not fully reflect the underlying reality. There have been only a few studies on patient satisfaction with male-to-female gender reassignment surgery. Methods: 254 consecutive patients who had undergone male-to-female gender reassignment surgery at Essen University Hospital’s Department of Urology retrospectively filled out a questionnaire about their subjective postoperative satisfaction. Results: 119 (46.9%) of the patients filled out and returned the questionnaires, at a mean of 5.05 years after surgery (standard deviation 1.61 years, range 1–7 years). 90.2% said their expectations for life as a woman were fulfilled postoperatively. 85.4% saw themselves as women. 61.2% were satisfied, and 26.2% very satisfied, with their outward appearance as a woman; 37.6% were satisfied, and 34.4% very satisfied, with the functional outcome. 65.7% said they were satisfied with their life as it is now. Conclusion: The very high rates of subjective satisfaction and the surgical outcomes indicate that gender reassignment surgery is beneficial. These findings must be interpreted with caution, however, because fewer than half of the questionnaires were returned.

Heylens et al., 2014

Heylens, G., Verroken, C., De Cock, S., T’Sjoen, G., & De Cuypere, G. (2014). Effects of different steps in gender reassignment therapy on psychopathology: a prospective study of persons with a gender identity disorder. The Journal of Sexual Medicine , 11 (1), 119–126.

Introduction: At the start of gender reassignment therapy, persons with a gender identity disorder (GID) may deal with various forms of psychopathology. Until now, a limited number of publications focus on the effect of the different phases of treatment on this comorbidity and other psychosocial factors. Aims: The aim of this study was to investigate how gender reassignment therapy affects psychopathology and other psychosocial factors. Methods: This is a prospective study that assessed 57 individuals with GID by using the Symptom Checklist‐90 (SCL‐90) at three different points of time: at presentation, after the start of hormonal treatment, and after sex reassignment surgery (SRS). Questionnaires on psychosocial variables were used to evaluate the evolution between the presentation and the postoperative period. The data were statistically analyzed by using SPSS 19.0, with significance levels set at P < 0.05. Main Outcome Measures: The psychopathological parameters include overall psychoneurotic distress, anxiety, agoraphobia, depression, somatization, paranoid ideation/psychoticism, interpersonal sensitivity, hostility, and sleeping problems. The psychosocial parameters consist of relationship, living situation, employment, sexual contacts, social contacts, substance abuse, and suicide attempt. Results: A difference in SCL‐90 overall psychoneurotic distress was observed at the different points of assessments (P = 0.003), with the most prominent decrease occurring after the initiation of hormone therapy (P < 0.001). Significant decreases were found in the subscales such as anxiety, depression, interpersonal sensitivity, and hostility. Furthermore, the SCL‐90 scores resembled those of a general population after hormone therapy was initiated. Analysis of the psychosocial variables showed no significant differences between pre‐ and postoperative assessments. Conclusions: A marked reduction in psychopathology occurs during the process of sex reassignment therapy, especially after the initiation of hormone therapy.

Imbimbo et al., 2009

Imbimbo, C., Verze, P., Palmieri, A., Longo, N., Fusco, F., Arcaniolo, D., & Mirone, V. (2009). A report from a single institute’s 14-year experience in treatment of male-to-female transsexuals. The Journal of Sexual Medicine , 6 (10), 2736–2745.

Introduction: Gender identity disorder or transsexualism is a complex clinical condition, and prevailing social context strongly impacts the form of its manifestations. Sex reassignment surgery (SRS) is the crucial step of a long and complex therapeutic process starting with preliminary psychiatric evaluation and culminating in definitive gender identity conversion. Aim: The aim of our study is to arrive at a clinical and psychosocial profile of male-to-female transsexuals in Italy through analysis of their personal and clinical experience and evaluation of their postsurgical satisfaction levels SRS. Methods: From January 1992 to September 2006, 163 male patients who had undergone gender-transforming surgery at our institution were requested to complete a patient satisfaction questionnaire. Main Outcome Measures: The questionnaire consisted of 38 questions covering nine main topics: general data, employment status, family status, personal relationships, social and cultural aspects, presurgical preparation, surgical procedure, and postsurgical sex life and overall satisfaction. Results: Average age was 31 years old. Seventy-two percent had a high educational level, and 63% were steadily employed. Half of the patients had contemplated suicide at some time in their lives before surgery and 4% had actually attempted suicide. Family and colleague emotional support levels were satisfactory. All patients had been adequately informed of surgical procedure beforehand. Eighty-nine percent engaged in postsurgical sexual activities. Seventy-five percent had a more satisfactory sex life after SRS, with main complications being pain during intercourse and lack of lubrication. Seventy-eight percent were satisfied with their neovagina’s esthetic appearance, whereas only 56% were satisfied with depth. Almost all of the patients were satisfied with their new sexual status and expressed no regrets. Conclusions: Our patients’ high level of satisfaction was due to a combination of a well-conducted preoperative preparation program, competent surgical skills, and consistent postoperative follow-up.

Johansson et al., 2010

Johansson, A., Sundbom, E., Höjerback, T., & Bodlund, O. (2010). A five-year follow-up study of Swedish adults with gender identity disorder. Archives of Sexual Behavior , 39 (6), 1429-1437.

This follow-up study evaluated the outcome of sex reassignment as viewed by both clinicians and patients, with an additional focus on the outcome based on sex and subgroups. Of a total of 60 patients approved for sex reassignment, 42 (25 male-to-female [MF] and 17 female-to-male [FM]) transsexuals completed a follow-up assessment after 5 or more years in the process or 2 or more years after completed sex reassignment surgery. Twenty-six (62%) patients had an early onset and 16 (38%) patients had a late onset; 29 (69%) patients had a homosexual sexual orientation and 13 (31%) patients had a non-homosexual sexual orientation (relative to biological sex). At index and follow-up, a semi-structured interview was conducted. At follow-up, 32 patients had completed sex reassignment surgery, five were still in process, and five—following their own decision—had abstained from genital surgery. No one regretted their reassignment. The clinicians rated the global outcome as favorable in 62% of the cases, compared to 95% according to the patients themselves, with no differences between the subgroups. Based on the follow-up interview, more than 90% were stable or improved as regards work situation, partner relations, and sex life, but 5–15% were dissatisfied with the hormonal treatment, results of surgery, total sex reassignment procedure, or their present general health. Most outcome measures were rated positive and substantially equal for MF and FM. Late-onset transsexuals differed from those with early onset in some respects: these were mainly MF (88 vs. 42%), older when applying for sex reassignment (42 vs. 28 years), and non-homosexually oriented (56 vs. 15%). In conclusion, almost all patients were satisfied with the sex reassignment; 86% were assessed by clinicians at follow-up as stable or improved in global functioning.

Keo-Meier et al., 2015

Keo-Meier, C. L., Herman, L. I., Reisner, S. L., Pardo, S. T., Sharp, C., & Babcock, J. C. (2015). Testosterone treatment and MMPI-2 improvement in transgender men: A prospective controlled study. Journal of Consulting and Clinical Psychology, 83 , 143-156.

Objective: Most transgender men desire to receive testosterone treatment in order to masculinize their bodies. In this study, we aimed to investigate the short-term effects of testosterone treatment on psychological functioning in transgender men. This is the 1st controlled prospective follow-up study to examine such effects. Method: We examined a sample of transgender men (n = 48) and nontransgender male (n = 53) and female (n = 62) matched controls (mean age = 26.6 years; 74% White). We asked participants to complete the Minnesota Multiphasic Personality Inventory (2nd ed., or MMPI–2; Butcher, Graham, Tellegen, Dahlstrom, & Kaemmer, 2001) to assess psychological functioning at baseline and at the acute posttreatment follow-up (3 months after testosterone initiation). Regression models tested (a) Gender × Time interaction effects comparing divergent mean response profiles across measurements by gender identity; (b) changes in psychological functioning scores for acute postintervention measurements, adjusting for baseline measures, comparing transgender men with their matched nontransgender male and female controls and adjusting for baseline scores; and (c) changes in meeting clinical psychopathological thresholds. Results: Statistically significant changes in MMPI–2 scale scores were found at 3-month follow-up after initiating testosterone treatment relative to baseline for transgender men compared with female controls (female template): reductions in Hypochondria (p < .05), Depression (p < .05), Hysteria (p < .05), and Paranoia (p < .01); and increases in Masculinity–Femininity scores (p < .01). Gender × Time interaction effects were found for Hysteria (p < .05) and Paranoia (p < .01) relative to female controls (female template) and for Hypochondria (p < .05), Depression (p < .01), Hysteria (p < .01), Psychopathic Deviate (p < .05), Paranoia (p < .01), Psychasthenia (p < .01), and Schizophrenia (p < .01) compared with male controls (male template). In addition, the proportion of transgender men presenting with co-occurring psychopathology significantly decreased from baseline compared with 3-month follow-up relative to controls (p < .05). Conclusions: Findings suggest that testosterone treatment resulted in increased levels of psychological functioning on multiple domains in transgender men relative to nontransgender controls. These findings differed in comparisons of transgender men with female controls using the female template and with male controls using the male template. No iatrogenic effects of testosterone were found. These findings suggest a direct positive effect of 3 months of testosterone treatment on psychological functioning in transgender men.

Kraemer et al., 2008

Kraemer, B., Delsignore, A., Schnyder, U., & Hepp, U. (2008). Body image and transsexualism. Psychopathology , 41 (2), 96-100.

Background: To achieve a detailed view of the body image of transsexual patients, an assessment of perception, attitudes and experiences about one’s own body is necessary. To date, research on the body image of transsexual patients has mostly covered body dissatisfaction with respect to body perception. Sampling and Methods: We investigated 23 preoperative (16 male-to-female and 7 female-to-male transsexual patients) and 22 postoperative (14 male-to-female and 8 female-to-male) transsexual patients using a validated psychological measure for body image variables. Results: We found that preoperative transsexual patients were insecure and felt unattractive because of concerns about their body image. However, postoperative transsexual patients scored high on attractiveness and self-confidence. Furthermore, postoperative transsexual patients showed low scores for insecurity and concerns about their body. Conclusions: Our results indicate an improvement of body image concerns for transsexual patients following standards of care for gender identity disorder. Follow-up studies are recommended to confirm the assumed positive outcome of standards of care on body image.

Landen et al., 1998

Landén, M., Wålinder, J., Hambert, G., & Lundström, B. (1998). Factors predictive of regret in sex reassignment. Acta Psychiatrica Scandinavica , 97 (4), 284-289.

The objective of this study was to evaluate the features and calculate the frequency of sex-reassigned subjects who had applied for reversal to their biological sex, and to compare these with non-regretful subjects. An inception cohort was retrospectively identified consisting of all subjects with gender identity disorder who were approved for sex reassignment in Sweden during the period 1972-1992. The period of time that elapsed between the application and this evaluation ranged from 4 to 24 years. The total cohort consisted of 218 subjects. The results showed that 3.8% of the patients who were sex reassigned during 1972-1992 regretted the measures taken. The cohort was subdivided according to the presence or absence of regret of sex reassignment, and the two groups were compared. The results of logistic regression analysis indicated that two factors predicted regret of sex reassignment, namely lack of support from the patient’s family, and the patient belonging to the non-core group of transsexuals. In conclusion, the results show that the outcome of sex reassignment has improved over the years. However, the identified risk factors indicate the need for substantial efforts to support the families and close friends of candidates for sex reassignment.

Lawrence, 2003

Lawrence, A. A. (2003). Factors associated with satisfaction or regret following male-to-female sex reassignment surgery. Archives of Sexual Behavior , 32 (4), 299-315.

This study examined factors associated with satisfaction or regret following sex reassignment surgery (SRS) in 232 male-to-female transsexuals operated on between 1994 and 2000 by one surgeon using a consistent technique. Participants, all of whom were at least 1-year postoperative, completed a written questionnaire concerning their experiences and attitudes. Participants reported overwhelmingly that they were happy with their SRS results and that SRS had greatly improved the quality of their lives. None reported outright regret and only a few expressed even occasional regret. Dissatisfaction was most strongly associated with unsatisfactory physical and functional results of surgery. Most indicators of transsexual typology, such as age at surgery, previous marriage or parenthood, and sexual orientation, were not significantly associated with subjective outcomes. Compliance with minimum eligibility requirements for SRS specified by the Harry Benjamin International Gender Dysphoria Association was not associated with more favorable subjective outcomes. The physical results of SRS may be more important than preoperative factors such as transsexual typology or compliance with established treatment regimens in predicting postoperative satisfaction or regret.

Lawrence, 2006

Lawrence, A. A. (2006). Patient-reported complications and functional outcomes of male-to-female sex reassignment surgery. Archives of Sexual Behavior , 35 (6), 717-727.

This study examined preoperative preparations, complications, and physical and functional outcomes of male-to-female sex reassignment surgery (SRS), based on reports by 232 patients, all of whom underwent penile-inversion vaginoplasty and sensate clitoroplasty, performed by one surgeon using a consistent technique. Nearly all patients discontinued hormone therapy before SRS and most reported that doing so created no difficulties. Preoperative electrolysis to remove genital hair, undergone by most patients, was not associated with less serious vaginal hair problems. No patients reported rectal-vaginal fistula or deep-vein thrombosis and reports of other significant surgical complications were uncommon. One third of patients, however, reported urinary stream problems. No single complication was significantly associated with regretting SRS. Satisfaction with most physical and functional outcomes of SRS was high; participants were least satisfied with vaginal lubrication, vaginal touch sensation, and vaginal erotic sensation. Frequency of achieving orgasm after SRS was not significantly associated with most general measures of satisfaction. Later years of surgery, reflecting greater surgeon experience, were not associated with lower prevalence rates for most complications or with better ratings for most physical and functional outcomes of SRS.

Lobato et al., 2006

Lobato M. I., Koff, W. J., Manenti, C., da Fonseca Seger, D., Salvador, J., et al. (2006). Follow-up of sex reassignment surgery in transsexuals: a Brazilian cohort.  Archives of Sexual Behavior, 35(6) , 711–715.

This study examined the impact of sex reassignment surgery on the satisfaction with sexual experience, partnerships, and relationship with family members in a cohort of Brazilian transsexual patients. A group of 19 patients who received sex reassignment between 2000 and 2004 (18 male- to-female, 1 female-to-male) after a two-year evaluation by a multidisciplinary team, and who agreed to participate in the study, completed a written questionnaire. Mean age at entry into the program was 31.21 ± 8.57 years and mean schooling was 9.2 ± 1.4 years. None of the patients reported regret for having undergone the surgery. Sexual experience was considered to have improved by 83.3% of the patients, and became more frequent for 64.7% of the patients. For 83.3% of the patients, sex was considered to be pleasurable with the neovagina/neopenis. In addition, 64.7% reported that initiating and maintaining a relationship had become easier. The number of patients with a partner increased from 52.6% to 73.7%. Family relationships improved in 26.3% of the cases, whereas 73.7% of the patients did not report a difference. None of the patients reported worse relationships

Manieri et al., 2014

Manieri, C., Castellano, E., Crespi, C., Di Bisceglie, C., Dell’Aquila, C., et al. (2014). Medical treatment of subjects with gender identity disorder: The experience in an Italian public health center. International Journal Of Transgenderism , 15 (2), 53-65.

Hormonal treatment is the main element during the transition program for transpeople. The aim of this paper is to describe the care and treatment of subjects, highlighting both the endocrine-metabolic effects of the hormonal therapy and the quality of life during the first year of cross-sex therapy in an Italian gender team. We studied 83 subjects (56 male-to-female [MtF], 27 female-to-male [FtM]) with hematological and hormonal evaluations every 3 months during the first year of hormonal therapy. MtF persons were treated with 17βestradiol and antiandrogens (cyproterone acetate, spironolactone, dutasteride); FtM persons were treated with transdermal or intramuscular testosterone. The WHO Quality of Life questionnaire was administered at the beginning and 1 year later. Hormonal changes paralleled phenotype modifications with wide variability. Most of both MtF and FtM subjects reported a statistically significant improvement in body image (p < 0.05). In particular, MtF subjects reported a statistically significant improvement in the quality of their sexual life and in the general quality of life (p < 0.05) 1 year after treatment initiation. Cross-sex therapy seems to be free of major risks in healthy subjects under clinical supervision during the first year. Selected subjects show an optimal adaptation to hormone-induced neuropsychological modifications and satisfaction regarding general and sexual life.

Megeri and Khoosal, 2007

Megeri, D., & Khoosal, D. (2007). Anxiety and depression in males experiencing gender dysphoria. Sexual & Relationship Therapy , 22 (1), 77-81.

Objective: The aim of the study was to compare anxiety and depression scores for the first 40 male to female people experiencing gender dysphoria attending the Leicester Gender Identity Clinic using the same sample as control pre and post gender realignment surgery. Hypothesis: There is an improvement in the scores of anxiety and depression following gender realignment surgery among people with gender dysphoria (male to female – transwomen). Results: There was no significant change in anxiety and depression scores in people with gender dysphoria (male to female) pre- and post-operatively.

Nelson, Whallett, & Mcgregor, 2009

Nelson, L., Whallett, E., & McGregor, J. (2009). Transgender patient satisfaction following reduction mammaplasty. Journal of Plastic, Reconstructive & Aesthetic Surgery , 62 (3), 331-334.

Aim: To evaluate the outcome of reduction mammaplasty in female-to-male transgender patients. Method: A 5-year retrospective review was conducted on all female-to-male transgender patients who underwent reduction mammaplasty. A postal questionnaire was devised to assess patient satisfaction, surgical outcome and psychological morbidity. Results: Seventeen patients were identified. The senior author performed bilateral reduction mammaplasties and free nipple grafts in 16 patients and one patient had a Benelli technique reduction. Complications included two haematomas, one wound infection, one wound dehiscence and three patients had hypertrophic scars. Secondary surgery was performed in seven patients and included scar revision, nipple reduction/realignment, dog-ear correction and nipple tattooing. The mean follow-up period after surgery was 10 months (range 2–23 months). Twelve postal questionnaires were completed (response rate 70%). All respondents expressed satisfaction with their result and no regret. Seven patients had nipple sensation and nine patients were satisfied with nipple position. All patients thought their scars were reasonable and felt that surgery had improved their self-confidence and social interactions. Conclusion: Reduction mammaplasty for female-to-male gender reassignment is associated with high patient satisfaction and a positive impact on the lives of these patients.

Newfield et al., 2006

Newfield, E., Hart, S., Dibble, S., & Kohler, L. (2006). Female-to-male transgender quality of life. Quality of Life Research , 15 (9), 1447-1457.

Objectives: We evaluated health-related quality of life in female-to-male (FTM) transgender individuals, using the Short-Form 36-Question Health Survey version 2 (SF-36v2). Methods: Using email, Internet bulletin boards, and postcards, we recruited individuals to an Internet site ( http://www.transurvey.org ), which contained a demographic survey and the SF36v2. We enrolled 446 FTM transgender and FTM transsexual participants, of which 384 were from the US. Results: Analysis of quality of life health concepts demonstrated statistically significant (p<0.0\) diminished quality of life among the FTM transgender participants as compared to the US male and female population, particularly in regard to mental health. FTM transgender participants who received testosterone (67%) reported statistically significant higher quality of life scores (/?<0.01) than those who had not received hormone therapy. Conclusions: FTM transgender participants reported significantly reduced mental health-related quality of life and

Padula, Heru, & Campbell, 2016

Padula, W. V., Heru, S. & Campbell, J. D. (2016). Societal implications of health insurance coverage for medically necessary services in the U.S. transgender population: A cost-effectiveness analysis. Journal of General Internal Medicine , 31 ( 4), 394-401.

Background: Recently, the Massachusetts Group Insurance Commission (GIC) prioritized research on the implications of a clause expressly prohibiting the denial of health insurance coverage for transgender-related services. These medically necessary services include primary and preventive care as well as transitional therapy. Objective: To analyze the cost-effectiveness of insurance coverage for medically necessary transgender-related services. Design: Markov model with 5- and 10-year time horizons from a U.S. societal perspective, discounted at 3 % (USD 2013). Data on outcomes were abstracted from the 2011 National Transgender Discrimination Survey (NTDS). Patients: U.S. transgender population starting before transitional therapy. Interventions: No health benefits compared to health insurance coverage for medically necessary services. This coverage can lead to hormone replacement therapy, sex reassignment surgery, or both. Main Measures: Cost per quality-adjusted life year (QALY) for successful transition or negative outcomes (e.g. HIV, depression, suicidality, drug abuse, mortality) dependent on insurance coverage or no health benefit at a willingness-to-pay threshold of $100,000/QALY. Budget impact interpreted as the U.S. per-member-per-month cost. Key Results: Compared to no health benefits for transgender patients ($23,619; 6.49 QALYs), insurance coverage for medically necessary services came at a greater cost and effectiveness ($31,816; 7.37 QALYs), with an incremental cost-effectiveness ratio (ICER) of $9314/QALY. The budget impact of this coverage is approximately $0.016 per member per month. Although the cost for transitions is $10,000–22,000 and the cost of provider coverage is $2175/year, these additional expenses hold good value for reducing the risk of negative endpoints —HIV, depression, suicidality, and drug abuse. Results were robust to uncertainty. The probabilistic sensitivity analysis showed that provider coverage was cost-effective in 85 % of simulations. Conclusions: Health insurance coverage for the U.S. transgender population is affordable and cost-effective, and has a low budget impact on U.S. society. Organizations such as the GIC should consider these results when examining policies regarding coverage exclusions.

Parola et al., 2010

Parola, N., Bonierbale, M., Lemaire, A., Aghababian, V., Michel, A., & Lançon, C. (2010). Study of quality of life for transsexuals after hormonal and surgical reassignment. Sexologies , 19 (1), 24-28.

Aim: The main objective of this work is to provide a more detailed assessment of the impact of surgical reassignment on the most important aspects of daily life for these patients. Our secondary objective was to establish the influence of various factors likely to have an impact on the quality of life (QoL), such as biological gender and the subject’s personality. Methods: A personality study was conducted using Eysenck Personality Inventory (EPI) so as to analyze two aspects of the personality (extraversion and neuroticism). Thirty-eight subjects who had undergone hormonal surgical reassignment were included in the study. Results: The results show that gender reassignment surgery improves the QoL for transsexuals in several different important areas: most are satisfied of their sexual reassignment (28/30), their social (21/30) and sexual QoL (25/30) are improved. However, there are differences between male-to-female (MtF) and female-to-male (FtM) transsexuals in terms of QoL: FtM have a better social, professional, friendly lifestyles than MtF. Finally, the results of this study did not evidence any influence by certain aspects of the personality, such as extraversion and neuroticism, on the QoL for reassigned subjects.

Pfäfflin, 1993

Pfäfflin, F. (1993). Regrets after sex reassignment surgery. Journal of Psychology & Human Sexuality , 5 (4), 69-85.

Using data draw from the follow-up literature covering the last 30 years, and the author’s clinical data on 295 men and women after SRS, an estimation of the number of patients who regretted the operations is made. Among female-to-male transsexuals after SRS, i.e., in men, no regrets were reported in the author’s sample, and in the literature they amount to less than 1%. Among male-to- female transsexuals after SRS, i.e., in women, regrets are reported in 1-1.5%. Poor differential diagnosis, failure to carry out the real-life- test, and poor surgical results seem to be the main reasons behind the regrets reported in the literature. According to three cases observed by the author in addition to personality traits the lack of proper care in treating the patients played a major role.

Pimenoff and Pfäfflin, 2011

Pimenoff, V., & Pfäfflin, F. (2011). Transsexualism: Treatment outcome of compliant and noncompliant patients. International Journal Of Transgenderism , 13 (1), 37-44.

The objective of the study was a follow-up of the treatment outcome of Finnish transsexuals who sought sex reassignment during the period 1970–2002 and a comparison of the results and duration of treatment of compliant and noncompliant patients. Fifteen male-to-female transsexuals and 17 female-to-male transsexuals who had undergone hormone and surgical treatment and legal sex reassignment in Finland completed a questionnaire on psychosocial data and on their experience with the different phases of clinical assessment and treatment. The changes in their vocational functioning and social and psychic adjustment were used as outcome indicators. The results and duration of the treatment of compliant and noncompliant patients were compared. The patients benefited significantly from treatment. The noncompliant patients achieved equally good results as the compliant ones, and did so in a shorter time. A good treatment outcome could be achieved even when the patient had told the assessing psychiatrist a falsified story of his life and sought hormone therapy, genital surgery, or legal sex reassignment on his own initiative without a recommendation from the psychiatrist. Based on these findings, it is recommended that the doctor-patient relationship be reconsidered and founded on frank cooperation.

Rakic et al., 1996

Rakic, Z., Starcevic, V., Maric, J., & Kelin, K. (1996). The outcome of sex reassignment surgery in Belgrade: 32 patients of both sexes. Archives of Sexual Behavior , 25 (5), 515-525.

Several aspects of the quality of life after sex reassignment surgery in 32 transsexuals of both sexes (22 men, 10 women) were examined. The Belgrade Team for Gender Identity Disorders designed a standardized questionnaire for this purpose. The follow-up period after operation was from 6 months to 4 years, and four aspects of the quality of life were examined: attitude towards the patients’ own body, relationships with other people, sexual activity, and occupational functioning. In most transsexuals, the quality of life was improved after surgery inasmuch as these four aspects are concerned. Only a few transsexuals were not satisfied with their life after surgery.

Rehman et al., 1999

Rehman, J., Lazer, S., Benet, A. E., Schaefer, L. C., & Melman, A. (1999). The reported sex and surgery satisfactions of 28 postoperative male-to-female transsexual patients. Archives of Sexual Behavior , 28 (1), 71-89.

From 1980 to July 1997 sixty-one male-to-female gender transformation surgeries were performed at our university center by one author (A.M.). Data were collected from patients who had surgery up to 1994 (n = 47) to obtain a minimum follow-up of 3 years; 28 patients were contacted. A mail questionnaire was supplemented by personal interviews with 11 patients and telephone interviews with remaining patients to obtain and clarify additional information. Physical and functional results of surgery were judged to be good, with few patients requiring additional corrective surgery. General satisfaction was expressed over the quality of cosmetic (normal appearing genitalia) and functional (ability to perceive orgasm) results. Follow-up showed satisfied who believed they had normal appearing genitalia and the ability to experience orgasm. Most patients were able to return to their jobs and live a more satisfactory social and personal life. One significant outcome was the importance of proper preparation of patients for surgery and especially the need for additional postoperative psychotherapy. None of the patients regretted having had surgery. However, some were, to a degree, disappointed because of difficulties experienced post operatively in adjusting satisfactorily as women both in their relationships with men and in living their lives generally as women. Findings of this study make a strong case for making a change in the Harry Benjamin Standards of Care to include a period of postoperative psychotherapy.

Rotondi et al., 2011

Rotondi, N. K., Bauer, G. R., Scanlon, K., Kaay, M., Travers, R., & Travers, A. (2011). Prevalence of and risk and protective factors for depression in female-to-male transgender Ontarians: Trans PULSE Project. Canadian Journal Of Community Mental Health , 30 (2), 135-155.

Although depression is understudied in transgender and transsexual communities, high prevalences have been reported. This paper presents original research from the Trans PULSE Project, an Ontario-wide, community-based initiative that surveyed 433 participants using respondent-driven sampling. The purpose of this analysis was to determine the prevalence of, and risk and protective factors for, depression among female-to-male (FTM) Ontarians (n = 207). We estimate that 66.4% of FTMs have symptomatology consistent with depression. In multivariable analyses, sexual satisfaction was a strong protective factor. Conversely, experiencing transphobia and being at the stage of planning but not having begun a medical transition (hormones and/or surgery) adversely affected mental health in FTMs.

Ruppin and Pfäfflin, 2015

Ruppin, U., & Pfäfflin, F. (2015). Long-term follow-up of adults with gender identity disorder. Archives of Sexual Behavior , 44 (5), 1321-1329.

The aim of this study was to re-examine individuals with gender identity disorder after as long a period of time as possible. To meet the inclusion criterion, the legal recognition of participants’ gender change via a legal name change had to date back at least 10 years. The sample comprised 71 participants (35 MtF and 36 FtM). The follow-up period was 10–24 years with a mean of 13.8 years (SD = 2.78). Instruments included a combination of qualitative and quantitative methods: Clinical interviews were conducted with the participants, and they completed a follow-up questionnaire as well as several standardized questionnaires they had already filled in when they first made contact with the clinic. Positive and desired changes were determined by all of the instruments: Participants reported high degrees of well-being and a good social integration. Very few participants were unemployed, most of them had a steady relationship, and they were also satisfied with their relationships with family and friends. Their overall evaluation of the treatment process for sex reassignment and its effectiveness in reducing gender dysphoria was positive. Regarding the results of the standardized questionnaires, participants showed significantly fewer psychological problems and interpersonal difficulties as well as a strongly increased life satisfaction at follow-up than at the time of the initial consultation. Despite these positive results, the treatment of transsexualism is far from being perfect.

Smith et al., 2005

Smith, Y. L. S., Van Goozen, S. H. M., Kuiper, A. J., & Cohen-Kettenis, P. (2005). Sex reassignment: Outcomes and predictors of treatment for adolescent and adult transsexuals. Psychological Medicine, 35 (1), 89-99.

Background: We prospectively studied outcomes of sex reassignment, potential differences between subgroups of transsexuals, and predictors of treatment course and outcome. Method: Altogether 325 consecutive adolescent and adult applicants for sex reassignment participated: 222 started hormone treatment, 103 did not; 188 completed and 34 dropped out of treatment. Only data of the 162 adults were used to evaluate treatment. Results between subgroups were compared to determine post-operative differences. Adults and adolescents were included to study predictors of treatment course and outcome. Results were statistically analysed with logistic regression and multiple linear regression analyses. Results: After treatment the group was no longer gender dysphoric. The vast majority functioned quite well psychologically, socially and sexually. Two non-homosexual male-to-female transsexuals expressed regrets. Post-operatively, female-to-male and homosexual transsexuals functioned better in many respects than male-to-female and non-homosexual transsexuals. Eligibility for treatment was largely based upon gender dysphoria, psychological stability, and physical appearance. Male-to-female transsexuals with more psychopathology and cross-gender symptoms in childhood, yet less gender dysphoria at application, were more likely to drop out prematurely. Non-homosexual applicants with much psychopathology and body dissatisfaction reported the worst post-operative outcomes. Conclusions: The results substantiate previous conclusions that sex reassignment is effective. Still, clinicians need to be alert for non-homosexual male-to-females with unfavourable psychological functioning and physical appearance and inconsistent gender dysphoria reports, as these are risk factors for dropping out and poor post-operative results. If they are considered eligible, they may require additional therapeutic guidance during or even after treatment.

van de Grift et al., 2017

van de Grift, T. C., Elaut, E., Cerwenka, S. C., Cohen-Kettenis, P. T., Cuypere, G. D., Richter-Appelt, H., & Kreukels, B. P. (2017). Effects of medical interventions on gender dysphoria and body image. Psychosomatic Medicine , 79 (7), 815-823.

Objective: The aim of this study from the European Network for the Investigation of Gender Incongruence is to investigate the status of all individuals who had applied for gender confirming interventions from 2007 to 2009, irrespective of whether they received treatment. The current article describes the study protocol, the effect of medical treatment on gender dysphoria and body image, and the predictive value of (pre)treatment factors on posttreatment outcomes. Methods: Data were collected on medical interventions, transition status, gender dysphoria (Utrecht Gender Dysphoria Scale), and body image (Body Image Scale for transsexuals). In total, 201 people participated in the study (37% of the original cohort). Results: At follow-up, 29 participants (14%) did not receive medical interventions, 36 hormones only (18%), and 136 hormones and surgery (68%). Most transwomen had undergone genital surgery, and most transmen chest surgery. Overall, the levels of gender dysphoria and body dissatisfaction were significantly lower at follow-up compared with clinical entry. Satisfaction with therapy responsive and unresponsive body characteristics both improved. High dissatisfaction at admission and lower psychological functioning at follow-up were associated with persistent body dissatisfaction. Conclusions: Hormone-based interventions and surgery were followed by improvements in body satisfaction. The level of psychological symptoms and the degree of body satisfaction at baseline were significantly associated with body satisfaction at follow-up.

van de Grift, T. C., Elaut, E., Cerwenka, S. C., Cohen-Kettenis, P. T., & Kreukels, B. P. (2017). Surgical satisfaction, quality of life, and their association after gender-affirming surgery: A follow-up study. Journal of Sex & Marital Therapy , 44 (2), 138-148.

We assessed the outcomes of gender-affirming surgery (GAS, or sex-reassignment surgery) 4 to 6 years after first clinical contact, and the associations between postoperative (dis)satisfaction and quality of life (QoL). Our multicenter, cross-sectional follow-up study involved persons diagnosed with gender dysphoria (DSM-IV-TR) who applied for medical interventions from 2007 until 2009. Of 546 eligible persons, 201 (37%) responded, of whom 136 had undergone GAS (genital, chest, facial, vocal cord and/or thyroid cartilage surgery). Main outcome measures were procedure performed, self-reported complications, and satisfaction with surgical outcomes (standardized questionnaires), QoL (Satisfaction With Life Scale, Subjective Happiness Scale, Cantril Ladder), gender dysphoria (Utrecht Gender Dysphoria Scale), and psychological symptoms (Symptom Checklist-90). Postoperative satisfaction was 94% to 100%, depending on the type of surgery performed. Eight (6%) of the participants reported dissatisfaction and/or regret, which was associated with preoperative psychological symptoms or self-reported surgical complications (OR= 6.07). Satisfied respondents’ QoL scores were similar to reference values; dissatisfied or regretful respondents’ scores were lower. Therefore, dissatisfaction after GAS may be viewed as indicator of unfavorable psychological and QoL outcomes.

Vujovic et al., 2009

Vujovic, S., Popovic, S., Sbutega-Milosevic, G., Djordjevic, M., & Gooren, L. (2009). Transsexualism in Serbia: A twenty-year follow-up study. The Journal of Sexual Medicine , 6 (4), 1018-1023.

Introduction: Gender dysphoria occurs in all societies and cultures. The prevailing social context has a strong impact on its manifestations as well as on applications by individuals with the condition for sex reassignment treatment. Aim: To describe a transsexual population seeking sex reassignment treatment in Serbia, part of former Yugoslavia. Methods: Data, collated over a period of 20 years, from subjects applying for sex reassignment to the only center in Serbia, were analyzed retrospectively. Main Outcome Measures: Age at the time of application, demographic data, family background, sex ratio, the prevalence of polycystic ovarian syndrome (PCOS) among female-to-male (FTM) transsexuals, and readiness to undergo surgical sex reassignment were tabulated. Results: Applicants for sex reassignment in Serbia are relatively young. The sex ratio is close to 1:1. They often come from single-child families. More than 10% do not wish to undergo surgical sex reassignment. The prevalence of PCOS among FTM transsexuals was higher than in the general population but considerably lower than that reported in the literature from other populations. Of those who had undergone sex reassignment, none expressed regret for their decision. Conclusions: Although transsexualism is a universal phenomenon, the relatively young age of those applying for sex reassignment and the sex ratio of 1:1 distinguish the population in Serbia from others reported in the literature.

Weigert et al., 2013

Weigert, R., Frison, E., Sessiecq, Q., Al Mutairi, K., & Casoli, V. (2013). Patient satisfaction with breasts and psychosocial, sexual, and physical well-being after breast augmentation in male-to-female transsexuals. Plastic and Reconstructive Surgery, 132 (6), 1421-1429.

Background: Satisfaction with breasts, sexual well-being, psychosocial well-being, and physical well-being are essential outcome factors following breast augmentation surgery in male-to-female transsexual patients. The aim of this study was to measure change in patient satisfaction with breasts and sexual, physical, and psychosocial well-being after breast augmentation in male-to-female transsexual patients. Methods: All consecutive male-to-female transsexual patients who underwent breast augmentation between 2008 and 2012 were asked to complete the BREAST-Q Augmentation module questionnaire before surgery, at 4 months, and later after surgery. A prospective cohort study was designed and postoperative scores were compared with baseline scores. Satisfaction with breasts and sexual, physical, and psychosocial outcomes assessment was based on the BREAST-Q. Results: Thirty-five male-to-female transsexual patients completed the questionnaires. BREAST-Q subscale median scores (satisfaction with breasts, +59 points; sexual well-being, +34 points; and psychosocial well-being, +48 points) improved significantly (p < 0.05) at 4 months postoperatively and later. No significant change was observed in physical well-being. Conclusions: In this prospective, noncomparative, cohort study, the current results suggest that the gains in breast satisfaction, psychosocial well-being, and sexual well-being after male-to-female transsexual patients undergo breast augmentation are statistically significant and clinically meaningful to the patient at 4 months after surgery and in the long term.

Weyers et al., 2009

Weyers, S., Elaut, E., De Sutter, P., Gerris, J., T’Sjoen, G., et al. (2009). Long-term assessment of the physical, mental, and sexual health among transsexual women. The Journal of Sexual Medicine , 6 (3), 752-760.

Introduction: Transsexualism is the most extreme form of gender identity disorder and most transsexuals eventually pursue sex reassignment surgery (SRS). In transsexual women, this comprises removal of the male reproductive organs, creation of a neovagina and clitoris, and often implantation of breast prostheses. Studies have shown good sexual satisfaction after transition. However, long-term follow-up data on physical, mental and sexual functioning are lacking. Aim: To gather information on physical, mental, and sexual well-being, health-promoting behavior and satisfaction with gender-related body features of transsexual women who had undergone SRS. Methods: Fifty transsexual women who had undergone SRS >or=6 months earlier were recruited. Main Outcome Measures: Self-reported physical and mental health using the Dutch version of the Short-Form-36 (SF-36) Health Survey; sexual functioning using the Dutch version of the Female Sexual Function Index (FSFI). Satisfaction with gender-related bodily features as well as with perceived female appearance; importance of sex, relationship quality, necessity and advisability of gynecological exams, as well as health concerns and feelings of regret concerning transition were scored. Results: Compared with reference populations, transsexual women scored good on physical and mental level (SF-36). Gender-related bodily features were shown to be of high value. Appreciation of their appearance as perceived by others, as well as their own satisfaction with their self-image as women obtained a good score (8 and 9, respectively). However, sexual functioning as assessed through FSFI was suboptimal when compared with biological women, especially the sublevels concerning arousal, lubrication, and pain. Superior scores concerning sexual function were obtained in those transsexual women who were in a relationship and in heterosexuals. Conclusions: Transsexual women function well on a physical, emotional, psychological and social level. With respect to sexuality, they suffer from specific difficulties, especially concerning arousal, lubrication, and pain.

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Below are 4 studies that contain mixed or null findings on the effect of gender transition on transgender well-being. Click here to jump to the 17 studies that consist of literature reviews or guidelines that help advance knowledge about the effect of gender transition on transgender well-being . Click here to jump to the 51 studies that found that gender transition improves the well-being of transgender people .

Barrett, 1998.

Barrett J. (1998). Psychological and social function before and after phalloplasty. The International Journal of Transgenderism , 2 (1), 1-8.

There are no quantitative assessments of the benefits of phalloplasty in a female transsexual population. The study addresses this question, comparing transsexuals accepted for such surgery with transsexuals after such surgery has been performed. A population of 23 transsexuals accepted for phalloplasty was compared to a population of 40 who had undergone such surgery between six and one hundred and sixty months previously. The General Health Questionnaire (GHQ), Symptom Checklist 90 (SCL-90), Bem Sex Role Inventory and Social Role Performance Schedule (SRPS) were employed. Additionally, a questionnaire assessing satisfaction with cosmetic appearance, sexual function, relationship and urinary function was used, along with a semi-structured interview quantifying alcohol, cigarette and drug usage, and current sexual practice. There were significant differences between the populations. The post operative group showed higher depression ratings on the depression subscale of the GHQ. The masculine pre-operative Bem scores were neutral post-operatively as feminine sub-scores increased. There was improved satisfaction with genital appearance post-operatively, but satisfaction with relationships fell, although to a non-significant extent. Most other changes were in the expected direction but did not achieve significance. Transsexuals accepted for phalloplasty have very good psychological health. Tendency to further improvement is the case after phalloplasty. Depression is commoner, however, and quality of relationships declines somewhat, perhaps in consequence. Surgeons might advise partners as well as patients of realistic expectations from such surgery.

Lindqvist et al., 2017

Lindqvist, E. K., Sigurjonsson, H., Möllermark, C., Rinder, J., Farnebo, F., et al. (2017). Quality of life improves early after gender reassignment surgery in transgender women. European Journal of Plastic Surgery , 40 (3), 223-226.

Background: Few studies have examined the long-term quality of life (QoL) of individuals with gender dysphoria, or how it is affected by treatment. Our aim was to examine the QoL of transgender women undergoing gender reassignment surgery (GRS). Methods: We performed a prospective cohort study on 190 patients undergoing male-to-female GRS at Karolinska University Hospital between 2003 and 2015. We used the Swedish version of the Short Form-36 Health Survey (SF-36), which measures QoL across eight domains. The questionnaire was distributed to patients pre-operatively, as well as 1, 3, and 5 years post-operatively. The results were compared between the different measure points, as well as between the study group and the general population. Results: On most dimensions of the SF-36 questionnaire, transgender women reported a lower QoL than the general population. The scores of SF-36 showed a non-significant trend to be lower 5 years post-GRS compared to pre-operatively, a decline consistent with that of the general population. Self-perceived health compared to 1 year previously rose in the first post-operative year, after which it declined. Conclusions: To our knowledge, this is the largest prospective study to follow a group of transgender patients with regards to QoL over continuous temporal measure points. Our results show that transgender women generally have a lower QoL compared to the general population. GRS leads to an improvement in general well-being as a trend but over the long-term, QoL decreases slightly in line with that of the comparison group. Level of evidence: Level III, therapeutic study.

Simonsen et al., 2016

Simonsen, R. K., Giraldi, A., Kristensen, E., & Hald, G. M. (2016). Long-term follow-up of individuals undergoing sex reassignment surgery: Psychiatric morbidity and mortality. Nordic Journal Of Psychiatry , 70 (4), 241-247.

Background: There is a lack of long-term register-based follow-up studies of sex-reassigned individuals concerning mortality and psychiatric morbidity. Accordingly, the present study investigated both mortality and psychiatric morbidity using a sample of individuals with transsexualism which comprised 98% (n = 104) of all individuals in Denmark. Aims: (1) To investigate psychiatric morbidity before and after sex reassignment surgery (SRS) among Danish individuals who underwent SRS during the period of 1978–2010. (2) To investigate mortality among Danish individuals who underwent SRS during the period of 1978–2010.Method: Psychiatric morbidity and mortality were identified by data from the Danish Psychiatric Central Research Register and the Cause of Death Register through a retrospective register study of 104 sex-reassigned individuals. Results: Overall, 27.9% of the sample were registered with psychiatric morbidity before SRS and 22.1% after SRS (p = not significant). A total of 6.7% of the sample were registered with psychiatric morbidity both before and after SRS. Significantly more psychiatric diagnoses were found before SRS for those assigned as female at birth. Ten individuals were registered as deceased post-SRS with an average age of death of 53.5 years. Conclusions: No significant difference in psychiatric morbidity or mortality was found between male to female and female to male (FtM) save for the total number of psychiatric diagnoses where FtM held a significantly higher number of psychiatric diagnoses overall. Despite the over-representation of psychiatric diagnoses both pre- and post-SRS the study found that only a relatively limited number of individuals had received diagnoses both prior to and after SRS. This suggests that generally SRS may reduce psychological morbidity for some individuals while increasing it for others.

Udeze, 2008

Udeze, B., Abdelmawla, N., Khoosal, D., & Terry, T. (2008). Psychological functions in male-to-female transsexual people before and after surgery. Sexual & Relationship Therapy , 23 (2), 141-145.

Patients with gender dysphoria (GD) suffer from a constant feeling of psychological discomfort related to their anatomical sex. Gender reassignment surgery (GRS) attempts to release this discomfort. The aim of this study was to compare the functioning of a cohort or patients with GD before and after GRS. We hypothesized that there would be an improvement in the scores of the self-administered SCL-90R following gender reassignment surgery among male-to-female people with gender dysphoria. We studied 40 patients with a DSM-IV diagnosis of Gender Identity Disorder (GID) who attended Leicester Gender Identity Clinic. We compared their functioning as measured by Symptom Check List-90R (SCL-90R) which was administered to 40 randomly selected male-to-female patients before and within six months after GRS using the same sample as control pre-and post-surgery. There was no significant change in the different sub-scales of the SCL-90R scores in patients with male-to-female GID pre- and within six months post-surgery. The results of the study showed that GRS had no significant effect on functioning as measured by SCL-90R within six months of surgery. Our study has the advantage of reducing inter-subject variability by using the same patients as their own control. This study may be limited by the duration of reassessment post-surgery. Further studies with larger sample size and using other psychosocial scales are needed to elucidate on the effectiveness of surgical intervention on psychosocial parameters in patients with GD.

Below are 17 studies that consist of literature reviews or guidelines that help advance knowledge about the effect of gender transition on transgender well-being. Click here to jump to the 4 studies that contain mixed or null findings on the effect of gender transition on transgender well-being. Click here Click here to jump to the 51 studies that found that gender transition improves the well-being of transgender people .

American psychological, 2015.

Guidelines for psychological practice with transgender and gender nonconforming people. (2015). American Psychologist, 70 (9), 832-864.

In 2015, the American Psychological Association adopted Guidelines for Psychological Practice with Transgender and Gender Nonconforming Clients in order to describe affirmative psychological practice with transgender and gender nonconforming (TGNC) clients. There are 16 guidelines in this document that guide TGNC-affirmative psychological practice across the lifespan, from TGNC children to older adults. The Guidelines are organized into five clusters: (a) foundational knowledge and awareness; (b) stigma, discrimination, and barriers to care; (c) lifespan development; (d) assessment, therapy, and intervention; and (e) research, education, and training. In addition, the guidelines provide attention to TGNC people across a range of gender and racial/ethnic identities. The psychological practice guidelines also attend to issues of research and how psychologists may address the many social inequities TGNC people experience.

Bockting et al., 2016

Bockting, W., Coleman, E., Deutsch, M. B., Guillamon, A., Meyer, W., et al. (2016). Adult development and quality of life of transgender and gender nonconforming people. Current Opinion in Endocrinology & Diabetes and Obesity , 23 (2), 188–197.

Purpose of review: Research on the health of transgender and gender nonconforming people has been limited with most of the work focusing on transition-related care and HIV. The present review summarizes research to date on the overall development and quality of life of transgender and gender nonconforming adults, and makes recommendations for future research. Recent findings: Pervasive stigma and discrimination attached to gender nonconformity affect the health of transgender people across the lifespan, particularly when it comes to mental health and well-being. Despite the related challenges, transgender and gender nonconforming people may develop resilience over time. Social support and affirmation of gender identity play herein a critical role. Although there is a growing awareness of diversity in gender identity and expression among this population, a comprehensive understanding of biopsychosocial development beyond the gender binary and beyond transition is lacking. Summary: Greater visibility of transgender people in society has revealed the need to understand and promote their health and quality of life broadly, including but not limited to gender dysphoria and HIV. This means addressing their needs in context of their families and communities, sexual and reproductive health, and successful aging. Research is needed to better understand what factors are associated with resilience and how it can be effectively promoted.

Byne et al., 2012

Byne, W., Bradley, S.J., Coleman, E., et al. (2012). Report of the American Psychiatric Association task force on treatment of gender identity disorder. Archives of Sexual Behavior, 41 (4): 759–796.

Both the diagnosis and treatment of Gender Identity Disorder (GID) are controversial. Although linked, they are separate issues and the DSM does not evaluate treatments. The Board of Trustees (BOT) of the American Psychiatric Association (APA), therefore, formed a Task Force charged to perform a critical review of the literature on the treatment of GID at different ages, to assess the quality of evidence pertaining to treatment, and to prepare a report that included an opinion as to whether or not sufficient credible literature exists for development of treatment recommendations by the APA. The literature on treatment of gender dysphoria in individuals with disorders of sex development was also assessed. The completed report was accepted by the BOT on September 11, 2011. The quality of evidence pertaining to most aspects of treatment in all subgroups was determined to be low; however, areas of broad clinical consensus were identified and were deemed sufficient to support recommendations for treatment in all subgroups. With subjective improvement as the primary outcome measure, current evidence was judged sufficient to support recommendations for adults in the form of an evidence-based APA Practice Guideline with gaps in the empirical data supplemented by clinical consensus. The report recommends that the APA take steps beyond drafting treatment recommendations. These include issuing position statements to clarify the APA’s position regarding the medical necessity of treatments for GID, the ethical bounds of treatments of gender variant minors, and the rights of persons of any age who are gender variant, transgender or transsexual.

Carroll, 1999

Carroll, R. A. (1999). Outcomes of treatment for gender dysphoria. Journal of Sex Education and Therapy , 24 (3), 128–136.

This paper reviews the empirical research on the psychosocial outcomes of treatment for gender dysphoria. Recent research has highlighted the heterogeneity of transgendered experiences. There are four possible outcomes for patients who present with the dilemma of gender dysphoria: an unresolved outcome, acceptance of one’s given gender, engaging in a cross-gender role on a part-time basis, and making a full-time transition to the other gender role. Clinical work, but not empirical research, suggests that some individuals with gender dysphoria may come to accept their given gender role through psychological treatment. Many individuals find that it is psychologically sufficient to express the transgendered part of themselves through such activities as cross-dressing or gender blending. The large body of research on the outcome of gender reassignment surgery indicates that, for the majority of those who undergo this process, the outcome is positive. Predictors of a good outcome include good pre-reassignment psychological adjustment, family support, at least 1 year of living in the desired role, consistent use of hormones, psychological treatment, and good surgical outcomes. The outcome literature provides strong support for adherence to the Standards of Care of the Harry Benjamin International Gender Dysphoria Association. Implications to be drawn from this research include an appreciation of the diversity of transgendered experience, the need for more research on non-reassignment resolutions to gender dysphoria, and the importance of assisting the transgendered individual to identify the resolution that best suits him or her.

Cohen-Kettenis and Gooren, 1999

Cohen-Kettenis, P. T., & Gooren, L. J. G. (1999). Transsexualism: A review of etiology, diagnosis and treatment. Journal of Psychosomatic Research , 46 (4), 315-333.

Transsexualism is considered to be the extreme end of the spectrum of gender identity disorders characterized by, among other things, a pursuit of sex reassignment surgery (SRS). The origins of transsexualism are still largely unclear. A first indication of anatomic brain differences between transsexuals and nontranssexuals has been found. Also, certain parental (rearing) factors seem to be associated with transsexualism. Some contradictory findings regarding etiology, psychopathology and success of SRS seem to be related to the fact that certain subtypes of transsexuals follow different developmental routes. The observations that psychotherapy is not helpful in altering a crystallized cross-gender identity and that certain transsexuals do not show severe psychopathology has led clinicians to adopt sex reassignment as a treatment option. In many countries, transsexuals are now treated according to the Standards of Care of the Harry Benjamin International Gender Dysphoria Association, a professional organization in the field of transsexualism. Research on postoperative functioning of transsexuals does not allow for unequivocal conclusions, but there is little doubt that sex reassignment substantially alleviates the suffering of transsexuals. However, SRS is no panacea. Psychotherapy may be needed to help transsexuals in adapting to the new situation or in dealing with issues that could not be addressed before treatment.

Coleman et al., 2012

Coleman, E., Bockting, W., Botzer, M., Cohen-Kettenis, P., DeCuypere, G., et al. (2012). Standards of care for the health of transsexual, transgender, and gender-nonconforming people, version 7. International Journal of Transgenderism , 13 (4), 165-232.

The Standards of Care (SOC) for the Health of Transsexual, Transgender, and Gender Nonconforming People is a publication of the World Professional Association for Transgender Health (WPATH). The overall goal of the SOC is to provide clinical guidance for health professionals to assist transsexual, transgender, and gender nonconforming people with safe and effective pathways to achieving lasting personal comfort with their gendered selves, in order to maximize their overall health, psychological well-being, and self-fulfillment. This assistance may include primary care, gynecologic and urologic care, reproductive options, voice and communication therapy, mental health services (e.g., assessment, counseling, psychotherapy), and hormonal and surgical treatments. The SOC are based on the best available science and expert professional consensus. Because most of the research and experience in this field comes from a North American and Western European perspective, adaptations of the SOC to other parts of the world are necessary. The SOC articulate standards of care while acknowledging the role of making informed choices and the value of harm reduction approaches. In addition, this version of the SOC recognizes that treatment for gender dysphoria i.e., discomfort or distress that is caused by a discrepancy between persons gender identity and that persons sex assigned at birth (and the associated gender role and/or primary and secondary sex characteristics) has become more individualized. Some individuals who present for care will have made significant self-directed progress towards gender role changes or other resolutions regarding their gender identity or gender dysphoria. Other individuals will require more intensive services. Health professionals can use the SOC to help patients consider the full range of health services open to them, in accordance with their clinical needs and goals for gender expression.

Committee on Health Care for Underserved, 2011

Committee Opinion No. 512: Health Care for Transgender Individuals. (2011). Obstetrics & Gynecology , 118 (6), 1454–1458.

Transgender individuals face harassment, discrimination, and rejection within our society. Lack of awareness, knowledge, and sensitivity in health care communities eventually leads to inadequate access to, underutilization of, and disparities within the health care system for this population. Although the care for these patients is often managed by a specialty team, obstetrician–gynecologists should be prepared to assist or refer transgender individuals with routine treatment and screening as well as hormonal and surgical therapies. The American College of Obstetricians and Gynecologists opposes discrimination on the basis of gender identity and urges public and private health insurance plans to cover the treatment of gender identity disorder.

Costa and Colizzi, 2016

Costa, R., & Colizzi, M. (2016). The effect of cross-sex hormonal treatment on gender dysphoria individuals’ mental health: A systematic review. Neuropsychiatric Disease and Treatment , 12 , 1953-1966.

Cross-sex hormonal treatment represents a main aspect of gender dysphoria health care pathway. However, it is still debated whether this intervention translates into a better mental well-being for the individual and which mechanisms may underlie this association. Although sex reassignment surgery has been the subject of extensive investigation, few studies have specifically focused on hormonal treatment in recent years. Here, we systematically review all studies examining the effect of cross-sex hormonal treatment on mental health and well-being in gender dysphoria. Research tends to support the evidence that hormone therapy reduces symptoms of anxiety and dissociation, lowering perceived and social distress and improving quality of life and self-esteem in both male-to-female and female-to-male individuals. Instead, compared to female-to-male individuals, hormone-treated male-to-female individuals seem to benefit more in terms of a reduction in their body uneasiness and personality-related psychopathology and an amelioration of their emotional functioning. Less consistent findings support an association between hormonal treatment and other mental health-related dimensions. In particular, depression, global psychopathology, and psychosocial functioning difficulties appear to reduce only in some studies, while others do not suggest any improvement in these domains. Results from longitudinal studies support more consistently the association between hormonal treatment and improved mental health. On the contrary, a number of cross-sectional studies do not support this evidence. This review provides possible biological explanation vs psychological explanation (direct effect vs indirect effect) for the hormonal treatment-induced better mental well-being. In conclusion, this review indicates that gender dysphoria-related mental distress may benefit from hormonal treatment intervention, suggesting a transient reaction to the nonsatisfaction connected to the incongruent body image rather than a stable psychiatric comorbidity. In this perspective, timely hormonal treatment intervention represents a crucial issue in gender dysphoria individuals’ mental health-related outcome.

Dhejne et al., 2016

Dhejne, C., Van Vlerken, R., Heylens, G., & Arcelus, J. (2016). Mental health and gender dysphoria: A review of the literature. International Review Of Psychiatry , 28 (1), 44-57.

Studies investigating the prevalence of psychiatric disorders among trans individuals have identified elevated rates of psychopathology. Research has also provided conflicting psychiatric outcomes following gender-confirming medical interventions. This review identifies 38 cross-sectional and longitudinal studies describing prevalence rates of psychiatric disorders and psychiatric outcomes, pre- and post-gender-confirming medical interventions, for people with gender dysphoria. It indicates that, although the levels of psychopathology and psychiatric disorders in trans people attending services at the time of assessment are higher than in the cis population, they do improve following gender-confirming medical intervention, in many cases reaching normative values. The main Axis I psychiatric disorders were found to be depression and anxiety disorder. Other major psychiatric disorders, such as schizophrenia and bipolar disorder, were rare and were no more prevalent than in the general population. There was conflicting evidence regarding gender differences: some studies found higher psychopathology in trans women, while others found no differences between gender groups. Although many studies were methodologically weak, and included people at different stages of transition within the same cohort of patients, overall this review indicates that trans people attending transgender health-care services appear to have a higher risk of psychiatric morbidity (that improves following treatment), and thus confirms the vulnerability of this population.

Gijs and Brewaeys, 2007

Gijs, L., & Brewaeys, A. (2007). Surgical treatment of gender dysphoria in adults and adolescents: Recent developments, effectiveness, and challenges. Annual Review of Sex Research , 18 (1), 178-224.

In 1990 Green and Fleming concluded that sex reassignment surgery (SRS) is an effective treatment for transsexuality because it reduced gender dysphoria drastically. Since 1990, many new outcome studies have been published, raising the question as to whether the conclusion of Green and Fleming still holds. After describing terminological and conceptual developments related to the treatment of gender identity disorder (GID), follow-up studies, including both adults and adolescents, of the outcomes of SRS are reviewed. Special attention is paid to the effects of SRS on gender dysphoria, sexuality, and regret. Despite methodological shortcomings of many of the studies, we conclude that SRS is an effective treatment for transsexualism and the only treatment that has been evaluated empirically with large clinical case series.

Gooren, 2011

Gooren, L. J. (2011). Care of transsexual persons. New England Journal of Medicine , 364 (13), 1251–1257.

This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author’s clinical recommendations. A healthy and successful 40-year-old man finds it increasingly difficult to live as a male. In childhood he preferred playing with girls and recalls feeling that he should have been one. Over time he has come to regard himself more and more as a female personality inhabiting a male body. After much agonizing, he has concluded that only sex reassignment can offer the peace of mind he craves. What would you advise? A healthy and successful 40-year-old man finds it increasingly difficult to live as a male. In childhood he preferred playing with girls and recalls feeling that he should have been one. Over time he has come to regard himself more and more as a female personality inhabiting a male body. After much agonizing, he has concluded that only sex reassignment can offer the peace of mind he craves. What would you advise?

Hembree et al., 2009

Hembree, W. C., Cohen-Kettenis, P., Delemarre-van de Waal, H. A., Gooren, L. J., Meyer, W., et al. (2009). Endocrine treatment of transsexual persons: An endocrine society clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism, 94 (9), 3132–3154.

Objective: The aim was to formulate practice guidelines for endocrine treatment of transsexual persons. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence, which was low or very low. Consensus Process: Committees and members of The Endocrine Society, European Society of Endocrinology, European Society for Paediatric Endocrinology, Lawson Wilkins Pediatric Endocrine Society, and World Professional Association for Transgender Health commented on preliminary drafts of these guidelines. Conclusions: Transsexual persons seeking to develop the physical characteristics of the desired gender require a safe, effective hormone regimen that will 1) suppress endogenous hormone secretion determined by the person’s genetic/biologic sex and 2) maintain sex hormone levels within the normal range for the person’s desired gender. A mental health professional (MHP) must recommend endocrine treatment and participate in ongoing care throughout the endocrine transition and decision for surgical sex reassignment. The endocrinologist must confirm the diagnostic criteria the MHP used to make these recommendations. Because a diagnosis of transsexualism in a prepubertal child cannot be made with certainty, we do not recommend endocrine treatment of prepubertal children. We recommend treating transsexual adolescents (Tanner stage 2) by suppressing puberty with GnRH analogues until age 16 years old, after which cross-sex hormones may be given. We suggest suppressing endogenous sex hormones, maintaining physiologic levels of gender-appropriate sex hormones and monitoring for known risks in adult transsexual persons. Endocrine treatment of transsexual persons should include suppression of endogenous sex hormones, physiologic levels of gender-appropriate sex hormones, and suppression of puberty in adolescents (Tanner stage 2).

Michel et al., 2002

Michel, A., Ansseau, M., Legros, J., Pitchot, W., & Mormont, C. (2002). The transsexual: What about the future? European Psychiatry , 17 (6), 353-362.

Since the 1950s, sexual surgical reassignments have been frequently carried out. As this surgical therapeutic procedure is controversial, it seems important to explore the actual consequences of such an intervention and objectively evaluate its relevance. In this context, we have carried out a review of the literature. After looking at the methodological limitations of follow-up studies, the psychological, sexual, social, and professional futures of the individuals subject to a transsexual operation are presented. Finally, prognostic aspects are considered. In the literature, follow-up studies tend to show that surgical transformations have positive consequences for the subjects. In the majority of cases, transsexuals are very satisfied with their intervention and any difficulties experienced are often temporary and disappear within a year after the surgical transformation. Studies show that there is less than 1% of regrets, and a little more than 1% of suicides among operated subjects. The empirical research does not confirm the opinion that suicide is strongly associated with surgical transformation.

Murad et al., 2010

Murad, M. H., Elamin, M. B., Garcia, M. Z., Mullan, R. J., Murad, A., Erwin, P. J., & Montori, V. M. (2010). Hormonal therapy and sex reassignment: A systematic review and meta-analysis of quality of life and psychosocial outcomes. Clinical Endocrinology , 72 (2), 214-231.

Objective: To assess the prognosis of individuals with gender identity disorder (GID) receiving hormonal therapy as a part of sex reassignment in terms of quality of life and other self‐reported psychosocial outcomes. Methods: We searched electronic databases, bibliography of included studies and expert files. All study designs were included with no language restrictions. Reviewers working independently and in pairs selected studies using predetermined inclusion and exclusion criteria, extracted outcome and quality data. We used a random‐effects meta‐analysis to pool proportions and estimate the 95% confidence intervals (CIs). We estimated the proportion of between‐study heterogeneity not attributable to chance using the I2 statistic. Results: We identified 28 eligible studies. These studies enrolled 1833 participants with GID (1093 male‐to‐female, 801 female‐to‐male) who underwent sex reassignment that included hormonal therapies. All the studies were observational and most lacked controls. Pooling across studies shows that after sex reassignment, 80% of individuals with GID reported significant improvement in gender dysphoria (95% CI = 68–89%; 8 studies; I2 = 82%); 78% reported significant improvement in psychological symptoms (95% CI = 56–94%; 7 studies; I2 = 86%); 80% reported significant improvement in quality of life (95% CI = 72–88%; 16 studies; I2 = 78%); and 72% reported significant improvement in sexual function (95% CI = 60–81%; 15 studies; I2 = 78%). Conclusions: Very low quality evidence suggests that sex reassignment that includes hormonal interventions in individuals with GID likely improves gender dysphoria, psychological functioning and comorbidities, sexual function and overall quality of life.

Reisner et al., 2016

Reisner, S. L., Poteat, T., Keatley, J., Cabral, M., Mothopeng, T., et al. (2016). Global health burden and needs of transgender populations: A review. The Lancet , 388 (10042), 412-436.

Transgender people are a diverse population affected by a range of negative health indicators across high-income, middle-income, and low-income settings. Studies consistently document a high prevalence of adverse health outcomes in this population, including HIV and other sexually transmitted infections, mental health distress, and substance use and abuse. However, many other health areas remain understudied, population-based representative samples and longitudinal studies are few, and routine surveillance efforts for transgender population health are scarce. The absence of survey items with which to identify transgender respondents in general surveys often restricts the availability of data with which to estimate the magnitude of health inequities and characterise the population-level health of transgender people globally. Despite the limitations, there are sufficient data highlighting the unique biological, behavioural, social, and structural contextual factors surrounding health risks and resiliencies for transgender people. To mitigate these risks and foster resilience, a comprehensive approach is needed that includes gender affirmation as a public health framework, improved health systems and access to health care informed by high quality data, and effective partnerships with local transgender communities to ensure responsiveness of and cultural specificity in programming. Consideration of transgender health underscores the need to explicitly consider sex and gender pathways in epidemiological research and public health surveillance more broadly.

Schmidt and Levine, 2015

Schmidt, L., & Levine, R. (2015). Psychological Outcomes and Reproductive Issues Among Gender Dysphoric Individuals. Endocrinology and Metabolism Clinics of North America , 44 (4), 773-785.

Gender dysphoria is a condition in which a person experiences discrepancy between the natal anatomic sex and the gender he or she identifies with, resulting in internal distress and a desire to live as the preferred gender. There is increasing demand for treatment, which includes suppression of puberty, cross-sex hormone therapy, and sex reassignment surgery. This article reviews longitudinal outcome data evaluating psychological well-being and quality of life among transgender individuals who have undergone cross-sex hormone treatment or sex reassignment surgery. Proposed methodologies for diagnosis and initiation of treatment are discussed, and the effects of cross-sex hormones and sex reassignment surgery on future reproductive potential.

White Hughto and Reisner, 2016

White Hughto, J. M., & Reisner, S. L. (2016). A systematic review of the effects of hormone therapy on psychological functioning and quality of life in transgender individuals. Transgender Health , 1 (1), 21–31.

Objectives: To review evidence from prospective cohort studies of the relationship between hormone therapy and changes in psychological functioning and quality of life in transgender individuals accessing hormone therapy over time. Data Sources: MEDLINE, PsycINFO, and PubMed were searched for relevant studies from inception to November 2014. Reference lists of included studies were hand searched. Results: Three uncontrolled prospective cohort studies, enrolling 247 transgender adults (180 male-to-female [MTF], 67 female-to-male [FTM]) initiating hormone therapy for the treatment of gender identity disorder (prior diagnostic term for gender dysphoria), were identified. The studies measured exposure to hormone therapy and subsequent changes in mental health (e.g., depression, anxiety) and quality of life outcomes at follow-up. Two studies showed a significant improvement in psychological functioning at 3–6 months and 12 months compared with baseline after initiating hormone therapy. The third study showed improvements in quality of life outcomes 12 months after initiating hormone therapy for FTM and MTF participants; however, only MTF participants showed a statistically significant increase in general quality of life after initiating hormone therapy. Conclusions: Hormone therapy interventions to improve the mental health and quality of life in transgender people with gender dysphoria have not been evaluated in controlled trials. Low quality evidence suggests that hormone therapy may lead to improvements in psychological functioning. Prospective controlled trials are needed to investigate the effects of hormone therapy on the mental health of transgender people.

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Gender identity

An overview of our work on gender identity.

Gender identity is a personal internal perception of oneself and, as such, the gender category with which a person identifies may not match the sex they were registered at birth. In contrast, sex is biologically determined.

Background to our work on gender identity

Our 2021 Census topic consultation identified a need amongst a number of data users for information about gender identity for policy development and service planning, especially in relation to the provision of health services. These requirements are strengthened by the need for information on those with the protected characteristic of gender reassignment as set out in the Equality Act 2010. The Gender identity topic report (PDF, 728KB) on the consultation findings provides further information.

Beyond our census work, we are currently engaging with the Government Statistical Service (GSS) Harmonisation team to develop a harmonised standard for collecting gender identity data for use across government departments.

Our current work includes:

• England and Wales 2021 Census gender question development
• harmonising with the devolved administrations
• cross-government gender identity and sexual orientation harmonisation work and the Government Equalities Office (GEO) LGBT Action Plan (PDF, 2.6MB) commitments
• Scottish Government working group on sex, gender and data
• work with the United Nations Economic Commission for Europe (UNECE) and other member countries to share approaches to measuring gender identity

Update to our work on the gender identity topic

Recommendation on gender identity for the 2021 census (december 2018).

The government published a white paper laying out the UK Statistics Authority’s proposals for the conduct and content of the 2021 Census . The proposals include a recommendation for the inclusion of a voluntary gender identity question, to be asked of those aged 16 years and over.

To coincide with this release, we published an update on our research and testing of questions for questions and topics for the 2021 Census . This report outlined the work we had done against each of the commitments in our Gender Identity Research and Testing Plan (PDF, 798KB) .

Harmonisation Champion network

The gender identity topic is represented at the Government Statistical Service Harmonisation Champion Network (this replaces the National Statistics Harmonisation Group (NSHG)).

For any queries regarding this work, please contact us by email at pop.info@ons.gov.uk or by phone on +44(0) 1329 444661.

Recent publications

June 2020, research reports on sex, gender identity and sexual orientation.

We published reports on Sex and gender identity question development for Census 2021 , and Exploring existing data on gender identity and sexual orientation .

September 2019, Guidance for questions on sex, gender identity and sexual orientation for the 2019 Census Rehearsal for the 2021 Census

We published a paper presenting the guidance for questions on sex, gender identity and sexual orientation for the 2019 Census Rehearsal for the 2021 Census, which includes a summary of the research that has informed the drafting of this guidance.

September 2019, Measuring sex in the UK censuses: harmonisation update

The Government Statistical Service (GSS) published the article Measuring sex in the UK censuses: Harmonisation update .

June 2019, In-depth review of measuring gender identity

The Office for National Statistics (ONS) and Statistics Canada (STC), as part of the UNECE Bureau of the Conference of European Statisticians, collaborated to undertake an In-depth review of measuring gender identity (paper published in June 2019). The review examines different approaches to statistical measurement of gender identity being undertaken so far, including the context and rationale; identifies issues and challenges; and provides some recommendations for the way forward.

February 2019, What is the difference between sex and gender?

This article sets out how “sex” and “gender” are used in the context of the UN Sustainable Development Goals (SDGs) .

Related publications

December 2017, 2021 census topic research report.

On 13 December 2017, we published an update of our gender identity research as part of the 2021 Census topic research report .

September 2017, Qualitative research on gender identity: phase 1 summary report

During March and April 2017, our Data Collection Methodology branch undertook focus groups and one-to-one in-depth interviews with transgender and cisgender participants. They explored issues around the collection of gender identity, including: responses to sex and gender questions and potential barriers to answering; terminology; privacy; burden and acceptability. In September 2017, we published a Qualitative research on gender identity: phase 1 summary report , which covers the purpose of the research, the methodology used, as well as findings, conclusions and recommendations. We will be undertaking phase 2 of the qualitative research in due course.

June 2017, Gender identity update event

As part of our ongoing stakeholder engagement, a Gender identity update event was held in June 2017. This provided our stakeholders with an update to our work so far. The event included an overview of work to date, findings from our research and testing, and next steps.

January 2017, Gender identity update paper

In January 2017, we published a Gender identity update , which outlines developments around the topic of gender identity since the publication of our Trans Data Position Paper (PDF, 186KB) in 2009. It covers legislation; Women and Equalities Committee inquiry into equality for transgender (trans) people; data collection and question development worldwide; and details of our research, testing and findings so far. It also sets out the next steps and future work we will be undertaking. A further update was published in autumn 2017 (see December 2017, 2021 Census topic research report ).

August 2016, Gender identity workshop

As the first stage of our stakeholder engagement, a Gender identity workshop was held in August 2016. This workshop enabled us to gain further understanding and clarity around concepts, terminology and information needs on gender identity.

May 2016, Gender identity working group

In May 2016, we established a working group to work with stakeholders and identify user needs for gender identity estimates.

You might also be interested in:

• Census 2021 Question development
• National Records of Scotland: Scotland’s Census 2021 Sex and Gender Identity Topic Report (PDF, 1.42MB)
• Sex and gender within the context of data collected for the Sustainable Development Goals (SDGs)
• UNECE: In-depth review of measuring gender identity
• Government Equalities Office (GEO)
• GEO: National LGBT Survey: Research report
• GEO: LGBT Action Plan 2018: Improving the lives of Lesbian, Gay, Bisexual and Transgender people
• GEO: National LGBT Survey Data Viewer
• Equality Act 2010

Related downloads

• Trans Data Position Paper (191.0 kB pdf)

• Introduction
• Conclusions
• Article Information

Error bars represent 95% CIs. GAS indicates gender-affirming surgery.

Percentages are based on the number of procedures divided by number of patients; thus, as some patients underwent multiple procedures the total may be greater than 100%. Error bars represent 95% CIs.

eTable.  ICD-10 and CPT Codes of Gender-Affirming Surgery

eFigure. Percentage of Patients With Codes for Gender Identity Disorder Who Underwent GAS

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Wright JD , Chen L , Suzuki Y , Matsuo K , Hershman DL. National Estimates of Gender-Affirming Surgery in the US. JAMA Netw Open. 2023;6(8):e2330348. doi:10.1001/jamanetworkopen.2023.30348

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National Estimates of Gender-Affirming Surgery in the US

• 1 Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, New York
• 2 Department of Obstetrics and Gynecology, University of Southern California, Los Angeles

Question   What are the temporal trends in gender-affirming surgery (GAS) in the US?

Findings   In this cohort study of 48 019 patients, GAS increased significantly, nearly tripling from 2016 to 2019. Breast and chest surgery was the most common class of procedures performed overall; genital reconstructive procedures were more common among older individuals.

Meaning   These findings suggest that there will be a greater need for clinicians knowledgeable in the care of transgender individuals with the requisite expertise to perform gender-affirming procedures.

Importance   While changes in federal and state laws mandating coverage of gender-affirming surgery (GAS) may have led to an increase in the number of annual cases, comprehensive data describing trends in both inpatient and outpatient procedures are limited.

Objective   To examine trends in inpatient and outpatient GAS procedures in the US and to explore the temporal trends in the types of GAS performed across age groups.

Design, Setting, and Participants   This cohort study includes data from 2016 to 2020 in the Nationwide Ambulatory Surgery Sample and the National Inpatient Sample. Patients with diagnosis codes for gender identity disorder, transsexualism, or a personal history of sex reassignment were identified, and the performance of GAS, including breast and chest procedures, genital reconstructive procedures, and other facial and cosmetic surgical procedures, were identified.

Main Outcome Measures   Weighted estimates of the annual number of inpatient and outpatient procedures performed and the distribution of each class of procedure overall and by age were analyzed.

Results   A total of 48 019 patients who underwent GAS were identified, including 25 099 (52.3%) who were aged 19 to 30 years. The most common procedures were breast and chest procedures, which occurred in 27 187 patients (56.6%), followed by genital reconstruction (16 872 [35.1%]) and other facial and cosmetic procedures (6669 [13.9%]). The absolute number of GAS procedures rose from 4552 in 2016 to a peak of 13 011 in 2019 and then declined slightly to 12 818 in 2020. Overall, 25 099 patients (52.3%) were aged 19 to 30 years, 10 476 (21.8%) were aged 31 to 40, and 3678 (7.7%) were aged12 to 18 years. When stratified by the type of procedure performed, breast and chest procedures made up a greater percentage of the surgical interventions in younger patients, while genital surgical procedures were greater in older patients.

Conclusions and Relevance   Performance of GAS has increased substantially in the US. Breast and chest surgery was the most common group of procedures performed. The number of genital surgical procedures performed increased with increasing age.

Gender dysphoria is characterized as an incongruence between an individual’s experienced or expressed gender and the gender that was assigned at birth. 1 Transgender individuals may pursue multiple treatments, including behavioral therapy, hormonal therapy, and gender-affirming surgery (GAS). 2 GAS encompasses a variety of procedures that align an individual patient’s gender identity with their physical appearance. 2 - 4

While numerous surgical interventions can be considered GAS, the procedures have been broadly classified as breast and chest surgical procedures, facial and cosmetic interventions, and genital reconstructive surgery. 2 , 4 Prior studies 2 - 7 have shown that GAS is associated with improved quality of life, high rates of satisfaction, and a reduction in gender dysphoria. Furthermore, some studies have reported that GAS is associated with decreased depression and anxiety. 8 Lastly, the procedures appear to be associated with acceptable morbidity and reasonable rates of perioperative complications. 2 , 4

Given the benefits of GAS, the performance of GAS in the US has increased over time. 9 The increase in GAS is likely due in part to federal and state laws requiring coverage of transition-related care, although actual insurance coverage of specific procedures is variable. 10 , 11 While prior work has shown that the use of inpatient GAS has increased, national estimates of inpatient and outpatient GAS are lacking. 9 This is important as many GAS procedures occur in ambulatory settings. We performed a population-based analysis to examine trends in GAS in the US and explored the temporal trends in the types of GAS performed across age groups.

To capture both inpatient and outpatient surgical procedures, we used data from the Nationwide Ambulatory Surgery Sample (NASS) and the National Inpatient Sample (NIS). NASS is an ambulatory surgery database and captures major ambulatory surgical procedures at nearly 2800 hospital-owned facilities from up to 35 states, approximating a 63% to 67% stratified sample of hospital-owned facilities. NIS comprehensively captures approximately 20% of inpatient hospital encounters from all community hospitals across 48 states participating in the Healthcare Cost and Utilization Project (HCUP), covering more than 97% of the US population. Both NIS and NASS contain weights that can be used to produce US population estimates. 12 , 13 Informed consent was waived because data sources contain deidentified data, and the study was deemed exempt by the Columbia University institutional review board. This cohort study followed the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline.

We selected patients of all ages with an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision ( ICD-10 ) diagnosis codes for gender identity disorder or transsexualism ( ICD-10 F64) or a personal history of sex reassignment ( ICD-10 Z87.890) from 2016 to 2020 (eTable in Supplement 1 ). We first examined all hospital (NIS) and ambulatory surgical (NASS) encounters for patients with these codes and then analyzed encounters for GAS within this cohort. GAS was identified using ICD-10 procedure codes and Common Procedural Terminology codes and classified as breast and chest procedures, genital reconstructive procedures, and other facial and cosmetic surgical procedures. 2 , 4 Breast and chest surgical procedures encompassed breast reconstruction, mammoplasty and mastopexy, or nipple reconstruction. Genital reconstructive procedures included any surgical intervention of the male or female genital tract. Other facial and cosmetic procedures included cosmetic facial procedures and other cosmetic procedures including hair removal or transplantation, liposuction, and collagen injections (eTable in Supplement 1 ). Patients might have undergone procedures from multiple different surgical groups. We measured the total number of procedures and the distribution of procedures within each procedural group.

Within the data sets, sex was based on patient self-report. The sex of patients in NIS who underwent inpatient surgery was classified as either male, female, missing, or inconsistent. The inconsistent classification denoted patients who underwent a procedure that was not consistent with the sex recorded on their medical record. Similar to prior analyses, patients in NIS with a sex variable not compatible with the procedure performed were classified as having undergone genital reconstructive surgery (GAS not otherwise specified). 9

Clinical variables in the analysis included patient clinical and demographic factors and hospital characteristics. Demographic characteristics included age at the time of surgery (12 to 18 years, 19 to 30 years, 31 to 40 years, 41 to 50 years, 51 to 60 years, 61 to 70 years, and older than 70 years), year of the procedure (2016-2020), and primary insurance coverage (private, Medicare, Medicaid, self-pay, and other). Race and ethnicity were only reported in NIS and were classified as White, Black, Hispanic and other. Race and ethnicity were considered in this study because prior studies have shown an association between race and GAS. The income status captured national quartiles of median household income based of a patient’s zip code and was recorded as less than 25% (low), 26% to 50% (medium-low), 51% to 75% (medium-high), and 76% or more (high). The Elixhauser Comorbidity Index was estimated for each patient based on the codes for common medical comorbidities and weighted for a final score. 14 Patients were classified as 0, 1, 2, or 3 or more. We separately reported coding for HIV and AIDS; substance abuse, including alcohol and drug abuse; and recorded mental health diagnoses, including depression and psychoses. Hospital characteristics included a composite of teaching status and location (rural, urban teaching, and urban nonteaching) and hospital region (Northeast, Midwest, South, and West). Hospital bed sizes were classified as small, medium, and large. The cutoffs were less than 100 (small), 100 to 299 (medium), and 300 or more (large) short-term acute care beds of the facilities from NASS and were varied based on region, urban-rural designation, and teaching status of the hospital from NIS. 8 Patients with missing data were classified as the unknown group and were included in the analysis.

National estimates of the number of GAS procedures among all hospital encounters for patients with gender identity disorder were derived using discharge or encounter weight provided by the databases. 15 The clinical and demographic characteristics of the patients undergoing GAS were reported descriptively. The number of encounters for gender identity disorder, the percentage of GAS procedures among those encounters, and the absolute number of each procedure performed over time were estimated. The difference by age group was examined and tested using Rao-Scott χ 2 test. All hypothesis tests were 2-sided, and P  < .05 was considered statistically significant. All analyses were conducted using SAS version 9.4 (SAS Institute Inc).

A total of 48 019 patients who underwent GAS were identified ( Table 1 ). Overall, 25 099 patients (52.3%) were aged 19 to 30 years, 10 476 (21.8%) were aged 31 to 40, and 3678 (7.7%) were aged 12 to 18 years. Private insurance coverage was most common in 29 064 patients (60.5%), while 12 127 (25.3%) were Medicaid recipients. Depression was reported in 7192 patients (15.0%). Most patients (42 467 [88.4%]) were treated at urban, teaching hospitals, and there was a disproportionate number of patients in the West (22 037 [45.9%]) and Northeast (12 396 [25.8%]). Within the cohort, 31 668 patients (65.9%) underwent 1 procedure while 13 415 (27.9%) underwent 2 procedures, and the remainder underwent multiple procedures concurrently ( Table 1 ).

The overall number of health system encounters for gender identity disorder rose from 13 855 in 2016 to 38 470 in 2020. Among encounters with a billing code for gender identity disorder, there was a consistent rise in the percentage that were for GAS from 4552 (32.9%) in 2016 to 13 011 (37.1%) in 2019, followed by a decline to 12 818 (33.3%) in 2020 ( Figure 1 and eFigure in Supplement 1 ). Among patients undergoing ambulatory surgical procedures, 37 394 (80.3%) of the surgical procedures included gender-affirming surgical procedures. For those with hospital admissions with gender identity disorder, 10 625 (11.8%) of admissions were for GAS.

Breast and chest procedures were most common and were performed for 27 187 patients (56.6%). Genital reconstruction was performed for 16 872 patients (35.1%), and other facial and cosmetic procedures for 6669 patients (13.9%) ( Table 2 ). The most common individual procedure was breast reconstruction in 21 244 (44.2%), while the most common genital reconstructive procedure was hysterectomy (4489 [9.3%]), followed by orchiectomy (3425 [7.1%]), and vaginoplasty (3381 [7.0%]). Among patients who underwent other facial and cosmetic procedures, liposuction (2945 [6.1%]) was most common, followed by rhinoplasty (2446 [5.1%]) and facial feminizing surgery and chin augmentation (1874 [3.9%]).

The absolute number of GAS procedures rose from 4552 in 2016 to a peak of 13 011 in 2019 and then declined slightly to 12 818 in 2020 ( Figure 1 ). Similar trends were noted for breast and chest surgical procedures as well as genital surgery, while the rate of other facial and cosmetic procedures increased consistently from 2016 to 2020. The distribution of the individual procedures performed in each class were largely similar across the years of analysis ( Table 3 ).

When stratified by age, patients 19 to 30 years had the greatest number of procedures, 25 099 ( Figure 2 ). There were 10 476 procedures performed in those aged 31 to 40 years and 4359 in those aged 41 to 50 years. Among patients younger than 19 years, 3678 GAS procedures were performed. GAS was less common in those cohorts older than 50 years. Overall, the greatest number of breast and chest surgical procedures, genital surgical procedures, and facial and other cosmetic surgical procedures were performed in patients aged 19 to 30 years.

When stratified by the type of procedure performed, breast and chest procedures made up the greatest percentage of the surgical interventions in younger patients while genital surgical procedures were greater in older patients ( Figure 2 ). Additionally, 3215 patients (87.4%) aged 12 to 18 years underwent GAS and had breast or chest procedures. This decreased to 16 067 patients (64.0%) in those aged 19 to 30 years, 4918 (46.9%) in those aged 31 to 40 years, and 1650 (37.9%) in patients aged 41 to 50 years ( P  < .001). In contrast, 405 patients (11.0%) aged 12 to 18 years underwent genital surgery. The percentage of patients who underwent genital surgery rose sequentially to 4423 (42.2%) in those aged 31 to 40 years, 1546 (52.3%) in those aged 51 to 60 years, and 742 (58.4%) in those aged 61 to 70 years ( P  < .001). The percentage of patients who underwent facial and other cosmetic surgical procedures rose with age from 9.5% in those aged 12 to 18 years to 20.6% in those aged 51 to 60 years, then gradually declined ( P  < .001). Figure 2 displays the absolute number of procedure classes performed by year stratified by age. The greatest magnitude of the decline in 2020 was in younger patients and for breast and chest procedures.

These findings suggest that the number of GAS procedures performed in the US has increased dramatically, nearly tripling from 2016 to 2019. Breast and chest surgery is the most common class of procedure performed while patients are most likely to undergo surgery between the ages of 19 and 30 years. The number of genital surgical procedures performed increased with increasing age.

Consistent with prior studies, we identified a remarkable increase in the number of GAS procedures performed over time. 9 , 16 A prior study examining national estimates of inpatient GAS procedures noted that the absolute number of procedures performed nearly doubled between 2000 to 2005 and from 2006 to 2011. In our analysis, the number of GAS procedures nearly tripled from 2016 to 2020. 9 , 17 Not unexpectedly, a large number of the procedures we captured were performed in the ambulatory setting, highlighting the need to capture both inpatient and outpatient procedures when analyzing data on trends. Like many prior studies, we noted a decrease in the number of procedures performed in 2020, likely reflective of the COVID-19 pandemic. 18 However, the decline in the number of procedures performed between 2019 and 2020 was relatively modest, particularly as these procedures are largely elective.

Analysis of procedure-specific trends by age revealed a number of important findings. First, GAS procedures were most common in patients aged 19 to 30 years. This is in line with prior work that demonstrated that most patients first experience gender dysphoria at a young age, with approximately three-quarters of patients reporting gender dysphoria by age 7 years. These patients subsequently lived for a mean of 23 years for transgender men and 27 years for transgender women before beginning gender transition treatments. 19 Our findings were also notable that GAS procedures were relatively uncommon in patients aged 18 years or younger. In our cohort, fewer than 1200 patients in this age group underwent GAS, even in the highest volume years. GAS in adolescents has been the focus of intense debate and led to legislative initiatives to limit access to these procedures in adolescents in several states. 20 , 21

Second, there was a marked difference in the distribution of procedures in the different age groups. Breast and chest procedures were more common in younger patients, while genital surgery was more frequent in older individuals. In our cohort of individuals aged 19 to 30 years, breast and chest procedures were twice as common as genital procedures. Genital surgery gradually increased with advancing age, and these procedures became the most common in patients older than 40 years. A prior study of patients with commercial insurance who underwent GAS noted that the mean age for mastectomy was 28 years, significantly lower than for hysterectomy at age 31 years, vaginoplasty at age 40 years, and orchiectomy at age 37 years. 16 These trends likely reflect the increased complexity of genital surgery compared with breast and chest surgery as well as the definitive nature of removal of the reproductive organs.

This study has limitations. First, there may be under-capture of both transgender individuals and GAS procedures. In both data sets analyzed, gender is based on self-report. NIS specifically makes notation of procedures that are considered inconsistent with a patient’s reported gender (eg, a male patient who underwent oophorectomy). Similar to prior work, we assumed that patients with a code for gender identity disorder or transsexualism along with a surgical procedure classified as inconsistent underwent GAS. 9 Second, we captured procedures commonly reported as GAS procedures; however, it is possible that some of these procedures were performed for other underlying indications or diseases rather than solely for gender affirmation. Third, our trends showed a significant increase in procedures through 2019, with a decline in 2020. The decline in services in 2020 is likely related to COVID-19 service alterations. Additionally, while we comprehensively captured inpatient and ambulatory surgical procedures in large, nationwide data sets, undoubtedly, a small number of procedures were performed in other settings; thus, our estimates may underrepresent the actual number of procedures performed each year in the US.

These data have important implications in providing an understanding of the use of services that can help inform care for transgender populations. The rapid rise in the performance of GAS suggests that there will be a greater need for clinicians knowledgeable in the care of transgender individuals and with the requisite expertise to perform GAS procedures. However, numerous reports have described the political considerations and challenges in the delivery of transgender care. 22 Despite many medical societies recognizing the necessity of gender-affirming care, several states have enacted legislation or policies that restrict gender-affirming care and services, particularly in adolescence. 20 , 21 These regulations are barriers for patients who seek gender-affirming care and provide legal and ethical challenges for clinicians. As the use of GAS increases, delivering equitable gender-affirming care in this complex landscape will remain a public health challenge.

Accepted for Publication: July 15, 2023.

Published: August 23, 2023. doi:10.1001/jamanetworkopen.2023.30348

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2023 Wright JD et al. JAMA Network Open .

Corresponding Author: Jason D. Wright, MD, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, 161 Fort Washington Ave, 4th Floor, New York, NY 10032 ( [email protected] ).

Author Contributions: Dr Wright had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Wright, Chen.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Wright.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Wright, Chen.

Administrative, technical, or material support: Wright, Suzuki.

Conflict of Interest Disclosures: Dr Wright reported receiving grants from Merck and personal fees from UpToDate outside the submitted work. No other disclosures were reported.

Data Sharing Statement: See Supplement 2 .

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Progression of gender dysphoria in children and adolescents: a longitudinal study.

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Stephanie Wagner , Leonidas Panagiotakopoulos , Rebecca Nash , Andrew Bradlyn , Darios Getahun , Timothy L. Lash , Douglas Roblin , Michael J. Silverberg , Vin Tangpricha , Suma Vupputuri , Michael Goodman; Progression of Gender Dysphoria in Children and Adolescents: A Longitudinal Study. Pediatrics July 2021; 148 (1): e2020027722. 10.1542/peds.2020-027722

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The progression of gender-expansive behavior to gender dysphoria and to gender-affirming hormonal treatment (GAHT) in children and adolescents is poorly understood.

A cohort of 958 gender-diverse (GD) children and adolescents who did not have a gender dysphoria–related diagnosis (GDRD) or GAHT at index were identified. Rates of first GDRD and first GAHT prescription were compared across demographic groups.

Overall, 29% of participants received a GDRD and 25% were prescribed GAHT during the average follow-up of 3.5 years (maximum 9 years). Compared with youth assigned male sex at birth, those assigned female sex at birth were more likely to receive a diagnosis and initiate GAHT with hazard ratio (95% confidence interval) estimates of 1.3 (1.0–1.7), and 2.5 (1.8–3.3), respectively. A progression to diagnosis was more common among those aged ≥15 years at initial presentation compared with those aged 10 to 14 years and those aged 3 to 9 years (37% vs 28% vs 16%, respectively). By using the youngest group as a reference, the adjusted hazard ratios (95% confidence interval) for a GDRD were 2.0 (1.3–3.0) for age 10 to 14 years and 2.7 (1.8–3.9) for age ≥15 years. Racial and ethnic minorities were less likely to receive a diagnosis or be prescribed GAHT.

This study characterized the progression of GD behavior in children and adolescents. Less than one-third of GD youth receive an eventual GDRD, and approximately one-quarter receive GAHT. Female sex at birth, older age of initial GD presentation to medical care, and non-Hispanic white race and ethnicity increased the likelihood of receiving diagnosis and treatment.

The progression of gender-expansive behavior to gender dysphoria and to gender-affirming hormonal treatment in children and adolescents is poorly understood. We do not yet know rates of conversion, diagnosis, or speed of progression to diagnosis.

In this study, we characterized the progression of gender-diverse behavior in children and adolescents.

Understanding the natural history of gender-expansive behavior is an increasingly important issue in caring for gender-diverse (GD) children and adolescents. Changing definitions, evolving theories of gender identity development, and availability of new data affect current understanding of the optimal care required to support GD youth.

The term “gender identity” refers to a wide range of individual self-identifications that may encompass various degrees of maleness or femaleness or a complete rejection of binary gender categories. GD individuals are those whose gender identity does not fully match their recorded sex at birth. 1   “Gender-variant behavior” is a related term that describes behaviors that contrast with what society may term as “typical” or “sex-typed.” 1   The language pertaining to individuals who experience distress with their assigned sex has changed in recent decades, and it continues to evolve, particularly with the introduction of the term “gender dysphoria” in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition to emphasize distress secondary to GD identity rather than pathologizing GD identity itself, 1 – 4   and the diagnosis of gender dysphoria as part of the International Classification of Diseases, 11th Revision , in which distress is no longer required, but must give access to gender-affirming medical treatment if necessary. 5   To date, no comprehensive longitudinal studies have characterized the progression of GD behaviors to gender dysphoria or related diagnosis.

The optimal age of starting gender-affirming therapies is an area of ongoing discussion. A strong scientific debate concerns optimal time for intervention because of some evidence indicating that childhood dysphoria might not still be equally present in adolescence 6   and other articles indicating that chances of attenuation of the gender nonconformity are considered to be much higher in the prepubertal compared with the pubertal youth. 7   Guidelines issued by the Endocrine Society and the World Professional Association for Transgender Health (WPATH) recommend psychosocial support and possible social transition for prepubescent children. 8 – 10   As children enter the period of early development of secondary sex characteristics, defined as Tanner stage 2, 11 , 12   guidelines recommend the use of gonadotropin-releasing hormone (GnRH) agonists to suppress continued puberty. The goals of hormone suppression are to (1) minimize dysphoria, (2) allow the safe passing of time before more definite decisions are made, and (3) facilitate gender affirmation later in life. 9 , 10   Both guidelines suggest initiating gender-affirming hormonal treatments (GAHTs) at ∼16 years of age but acknowledge that in many cases it may be appropriate to initiate earlier. 9 , 10 , 13   Access and affordability of these interventions vary across countries, health systems, and insurance plans. 8  

Practice guidelines for puberty suppression and GAHT are primarily based on consensus rather than high-quality empirical data. 9 , 10 , 13 – 18   The authors of these guidelines point out a lack of strong evidence in identifying the optimal age at which gender-affirming treatments should be initiated. 13 , 14 , 16  

Most available studies addressing the gender-affirming care offered to GD children and adolescents were based in individual clinics and included relatively small numbers (range: 25–187) of participants and nonuniformity in the design of subjects studied. 19 – 21   Moreover, little is known about the typical time course from initial presentation of GD behavior in children to initiation of gender-affirming care. 18 , 20 – 28   With the knowledge that the GD population is growing and increasing proportions of GD individuals are presenting at an earlier age, there is a need for large-scale longitudinal studies investigating patterns and determinants of GD-specific care in children and adolescents. 29 – 33   The purpose of this study was to examine the likelihood and predictors of receiving a GD-specific diagnosis and GAHT among youth who express gender-variant behavior. We used data from a large cohort of GD youth who received care within 3 integrated health care systems in the United States.

This study uses data from the Study of Transition, Outcomes, and Gender (STRONG) cohort. The STRONG cohort includes participants from Kaiser Permanente (KP) integrated health care systems in Georgia, Northern California, and Southern California. The 3 KP sites collectively provide comprehensive health care to ∼9 million individuals. 34 , 35   The current transgender health care protocols at KP follow the Endocrine Society and WPATH guidelines, which include mental health support, GnRH agonists, feminizing and masculinizing hormones, and surgery. 36   The Emory University Rollins School of Public Health served as the coordinating center. The study protocol received approvals from the institutional review boards of all 4 institutions (3 KP sites and the coordinating center) with exemption of informed consent. The details of STRONG cohort ascertainment and data collection were described in previous publications. 17 , 32 , 37   Participants were identified in the electronic health record from January 1, 2006, to December 31, 2014, by searching for keywords in free-text clinical notes reflecting GD behaviors. Each participant’s index date was defined on the basis of the first evidence of GD behaviors mentioned in the notes, as evidenced in the presence of keywords such as “transgender,” and “gender identity.” The full list of keywords can be found in our previous publication. 32   All notes were reviewed to confirm eligibility. The analytic data set was limited to participants who were aged <18 years at index date, had at least 1 follow-up appointment, and had evidence of GD behavior, as reflected in the keywords, but did not have a diagnosis related to gender dysphoria and had not received any GAHT. Participants whose sex recorded at birth could not be determined ( n = 14) were excluded from the analyses because sex recorded at birth was considered a key variable in the analyses. Two types of events of interest were ascertained during follow-up: an assignment of the first gender dysphoria–related diagnosis (GDRD) and receipt of GAHT. The GDRDs were based on the International Classification of Diseases, Ninth Revision and included codes for conditions such as transsexualism (302.5) and gender identity disorder in children (302.6). The Diagnostic and Statistical Manual of Mental Disorders uses the International Classification of Diseases coding scheme with direct match between the 2 systems. For this reason, any International Classification of Diseases codes used in this analysis would be equivalent to the same diagnosis in the contemporaneous Diagnostic and Statistical Manual of Mental Disorders . Cohort ascertainment and follow-up were undertaken before the health plans switched to International Classification of Diseases, 10th Revision codes. GAHT receipt was determined from pharmacy records and date of therapy initiation was based on the first prescription for a puberty suppression medication or cross-sex hormonal therapy.

The follow-up for each participant extended from the index date until the event of interest (diagnostic code or first ordered GAHT prescription, depending on the analysis), disenrollment from KP, or end of follow-up (December 31, 2014). The data were examined by using time-to-event analyses to take into account censoring and variable duration of follow-up.

Kaplan Meier curves were constructed to compare timing and occurrence of GDRD and GAHT initiation across subgroups of participants. The independent variables in these analyses included age category at index date (categorized as 3–9, 10–14 and ≥15–17 years), recorded sex at birth, and race and ethnicity (non-Hispanic white individuals versus individuals of other races and ethnicities). These age groups represent 3 distinct populations: children who have not started puberty, based on national averages (age 3–9 years); children after the onset of puberty who may be considered as candidates for puberty suppression (age 10–14 years); and teenagers who might be offered feminizing or masculinizing hormones on the basis of current treatment guidelines (age ≥15 years). 36  

Multivariable Cox proportional hazards models were used to evaluate the associations of all 3 independent variables (site, sex recorded at birth, age, and race and ethnicity) considered individually and simultaneously with each event of interest. The results of the Cox models were expressed as crude and adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). All models were evaluated for validity of proportional hazard assumptions by inspecting log-log curves. If proportional hazard assumptions were violated, stratified Cox models were used. The data analyses were performed by using SAS software version 9.4 (SAS Institute, Inc, Cary, NC).

After applying eligibility criteria ( Fig 1 ), 958 children were included in the final analysis data set ( Table 1 ). Of those, 431 individuals were assigned male sex at birth (AMAB) and 527 individuals were assigned female sex at birth (AFAB). Children aged <10 years at index date represented 21% of the total cohort, 30% of the AMAB group and 14% of the AFAB group. In both the AMAB and AFAB groups, non-Hispanic white individuals made up >45% of the children. A majority of individuals (63%) received care at KP Northern California. Of the total analytic cohort, 29% of participants received a GDRD and 25% were prescribed GAHT during an average follow-up of 3 years (maximum 9 years). Among 677 cohort members without a diagnosis, 74 (11%) received GAHT treatment, whereas, among 281 children and adolescent with a diagnosis, 162 (58%) initiated GAHT.

Inclusion and exclusion of individuals.

Selected Participant Characteristics by Recorded Sex at Birth

Column percentages.

Row percentages.

Compared with the AFAB group, a lower proportion of AMAB children and adolescents received a GDRD (24% vs 33%) or initiated GAHT (14% vs 33%) during follow-up ( Table 1 ). When time to diagnosis was compared across age groups among AMAB and AFAB children ( Fig 2A and C , respectively), the youngest age group (3–9 years of age) was most likely to remain diagnosis-free to the end of follow-up for both (85% in AMAB and 72% in AFAB). Among AMAB participants, the proportion of those who received a diagnosis before the end of follow-up was lower in the middle age group (10–14 years) than in the oldest age group (≥15 years) (20% vs 35%, respectively) ( Fig 2A ) but this was not the case among AFAB participants ( Fig 2C ). Whereas few of the youngest children received GAHT by the end of the follow-up (5% in the AFAB group and 4% in the AMAB group), treatment was generally more delayed in older AMAB than older AFAB children ( Fig 2B and D ).

Kaplan-Meier time-to-event analysis by age at index date stratified by sex recorded at birth. A, AMAB outcome: GDRD. B, AMAB outcome: GAHT. C, AFAB outcome: GDRD. D, AFAB outcome: GAHT.

In the multivariable model ( Table 2 ), the difference in diagnosis rates between AFAB and AMAB participants was attenuated (adjusted HR = 1.3; 95% CI: 1.0–1.7), but the difference in GAHT receipt remained evident (adjusted HR = 2.5; 95% CI: 1.8–3.3). By contrast, the differences in diagnosis rates remained pronounced across the 3 age groups; using the youngest age group (3–9 years) as reference, the adjusted HRs (95% CI) were 2.0 (1.3–3.0) for age 10 to 14 years and 2.7 (1.8–3.9) for age ≥15 years. The proportional hazard assumption for the age variables was violated in the analyses that used GAHT initiation as the end point of interest, and for this reason the corresponding adjusted HR estimates across the age groups were not generated by the model ( Table 2 ).

Results of Cox Proportional Models Evaluating Associations Between Participant Characteristics and Each Event of Interest

Model was stratified on age and study site because of violation of proportional hazards assumption for these 2 variables; for this reason, the results are controlled for age and study site, but no HR estimates are provided.

Includes persons with unknown race and ethnicity.

Relative to non-Hispanic white children, children of minority racial and ethnic groups were less likely to receive a GDRD (26% vs 33%) or be prescribed GAHT (21% vs 29%) during follow-up, and the time to diagnosis and GAHT were also different in the 2 groups ( Fig 3 ). Controlling for other variables ( Table 2 ), the difference in diagnosis rates was less evident (adjusted HR = 0.8; 95% CI: 0.6–1.0) whereas the difference in GAHT receipt was greater (adjusted HR = 0.6; 95% CI: 0.5–0.8).

Kaplan-Meier time-to-event analysis for non-Hispanic white individuals versus individuals of other races and ethnicities. A, Outcome: GDRD. B, Outcome: GAHT.

When the data were examined by site, rates of diagnosis appeared to be lower among children residing in Georgia compared with their California counterparts ( Fig 4 ). The HR estimates, however, were imprecise because of the small size of the KP Georgia cohort. The proportional hazard assumption for site variable was violated for GAHT initiation, and for this reason we controlled for site in the stratified Cox model, but the adjusted HR estimates for this variable are not presented ( Table 2 ).

Kaplan-Meier time-to-event analysis by study site. A, outcome: GDRD. B, outcome: GAHT. KP GA, Kaiser Permanente Georgia; KP NC, Kaiser Permanente Northern California; KP SC, Kaiser Permanente Southern California.

This electronic health record-based cohort study nested in 3 large integrated health care systems revealed that gender-expansive behaviors in most children do not lead to a GDRD and initiation of GAHT. We observed that the rates of diagnosis and GAHT initiation differed across demographic categories of participants and tended to be higher in (1) older adolescents, (2) AFAB cohort members, and (3) non-Hispanic white people. Because of the limited sample size, differences across study sites could not be definitively tested and no conclusion could be reached. In our cohort, data have overrepresentation from subjects who were AFAB, and, although this is also the case in more recent publications, 38 , 39   the skew toward subjects who were AFAB was not as pronounced as in those studies. This is likely due to the fact that our cohort dates back to 2006, and thus the difference is not as pronounced as in studies including subjects from more recent years.

Our results need to be viewed in the context of similar findings reported previously in European research. 21 , 28   Two similarly designed, but nonoverlapping, studies performed a follow-up assessment of children treated for gender dysphoria at a specialized clinic in the Netherlands. 21 , 28   The first study included 77 children who had been referred to a gender-specific clinic between 1989 and 2005 for gender dysphoria at age <12 years at initial presentation. 21   After an average follow-up of 10 years, 27% of the initial cohort continued experiencing gender dysphoria; however, this result may have been affected by the relatively high (30%) proportion of participants who did not respond to the survey. The authors also reported that individuals with gender dysphoria had more extreme gender dysphoria observed during childhood and were more likely to meet criteria for a gender dysphoria diagnosis during childhood. 21  

The second Dutch study originated from the same clinic but sampled a different group of adolescents ( n = 127) between 2000 and 2008. 28   As in the earlier study, participants received a GDRD at <12 years old and were followed-up at 15 years old or older. Approximately 37% of adolescents in the overall cohort still experienced gender dysphoria at follow-up, although a high percentage of nonrespondents (22%) were counted in the study as no longer experiencing gender dysphoria. It is noteworthy that this study did not record pubertal Tanner staging at enrollment; thus, although participants were all <12 years old, some could have been pubertal and some others prepubertal. Factors associated with unalleviated gender dysphoria included more pronounced dysphoria symptoms and older age at presentation. In addition, continuous gender dysphoria was more common among individuals who were AFAB. 28  

Both Dutch studies found that most participants did not experience gender dysphoria beyond puberty. This result is consistent with our observation that less than one-third of children presenting with GD behaviors received a GDRD and only approximately one-quarter initiated hormone therapy during follow-up. The Dutch researchers also reported a greater likelihood of unalleviated gender dysphoria in children who presented at an older age and among AFAB participants, both results in agreement with our findings.

Perhaps the most important methodologic feature of our study compared with previous research is the use of system-wide cohort ascertainment that was not limited to a particular clinical center. Although many of the transgender members of KP receive specialized coordinated care through Multispecialty Transitions Clinics, this was not an inclusion criterion in the study. Rather the present data set included any member with evidence of transgender status or gender diversity documented in the medical records. Thus, the resulting patient population represents an unselected group with diverse pathways to care. This may explain the relatively low percentage of GD children who received a GDRD, and the relatively high proportion of children who received care without a diagnosis. The deidentified data permitted inclusion of all eligible persons in the analyses because participation did not require subject opt-in. In addition, the keyword-based approach to identify eligible study participants offered a rare opportunity to evaluate the course of events in children at earlier stages of gender-variant behavior, which is rarely possible in specialized clinic-based studies.

The second methodologic feature that distinguishes our study from previously published studies conducted in the Netherlands is the more recent time period (1985–2008 vs 2006–2014). As the size and the composition of transgender populations are rapidly changing, especially in the youngest age groups, 40   it appears likely that the results may also be affected by sociopolitical and medical advances, increased access to medical care, less pronounced cultural stigma and evolving social norms with differential impact across generations. 41 – 44   On the other hand, greater awareness of the available gender-affirming care options, without adequate access to this care, may also exacerbate gender dysphoria.

Another notable aspect of the current study is the diverse sample and ability to examine racial and/or ethnic disparities in the care of GD children. We observed that non-Hispanic white participants had an earlier progression to diagnosis and a more rapid initiation of GAHT compared with other racial and ethnic groups. Although relative sparsity of data for specific racial and/or ethnic minority groups precluded a more granular examination of differences by race and/or ethnicity, our findings are in broad agreement with other studies that have shown cultural biases adversely affecting accessing care for gender dysphoria. 45 – 47   There was also a suggestion that geographical location may play a role; however, the analyses lacked power to evaluate modification by geographic region.

The observed disparities in receiving gender-affirming care may be the result of differences in attitudes toward gender diversity among children, their peers, and their families. 48 – 50   More broadly, a number of social factors, including political environment, culture, and religious taboos, may influence the degree to which GD children are accepted. 51 – 55   It is also possible that geographic region and/or ethnicity play a role in social acceptance and ability to access gender-affirming care. 56 – 58  

The difference in rates of diagnosis and especially treatment initiation between AMAB and AFAB children requires further investigation. Although some reports indicate that transgender boys and transgender girls experience differences in parental acceptance, 59   a more likely reason is that endogenous puberty occurs later in natal boys, and, because gender dysphoria typically worsens with pubertal progression, children who were AMAB might seek and receive gender-affirming care later than their AFAB counterparts. 60   Moreover, current Endocrine Society and WPATH guidelines recommend GAHT initiation once Tanner 2 stage is reached; this occurs on average later in AMAB children compared with their AFAB peers. 11 , 12   One could also argue that the observed disparity in GAHT initiation between AMAB and AFAB participants is attributable to the differences in the cost of therapy. Whereas the use of GnRH agonists is routinely preferred in AMAB youth, in AFAB children and adolescents use of contraception offers a cheaper alternative. Recently, use of GnRH agonists has expanded as it is increasingly covered by insurance plans 61   ; however, the cohort in the current study was followed to the end of 2014, which might have been just before this change in medical practice.

Although our findings indicate that most children with GD behaviors did not receive a GDRD and did not start GAHT during follow-up (3 years on average), these results cannot be interpreted as evidence of long-term outcomes. Thus, it is likely that the proportion of individuals who eventually start gender-affirming care will increase with extended follow-up; however, we expect that some GD study participants will remain dysphoria-free and not require intervention.

It is worth noting that the methodologic features of our study can be viewed as both its strengths and its weaknesses. Because the analyses were based exclusively on the information obtained from medical records, this design precluded collection of patient- and family-reported measures. As such, the degree of documentation by medical professionals can influence the index date and therefore the timing of follow-up initiation. Other limitations of our analyses include the lack of data on social environment or psychological support, pubertal status, and the inability to distinguish children who identify as transgender from those who present with nonbinary or other gender-nonconforming identities. In addition, GD children enrolled in integrated health care systems come primarily from families with health insurance and may not be representative of all GD youth in the United States. On the other hand, this cohort does include patients enrolled in Medicaid plans, allowing that at least some of the study participants come from populations with lower socioeconomic status. Although GAHT protocols do not differ substantially across study sites, the relatively long interval of data collection and follow-up (2006–2016) means that the therapeutic approaches changed over time, and thus children identified earlier in the study may have different pathways to care compared with their counterparts in more recent years.

Our analyses reveal that GD adolescents are more likely to receive a GDRD or hormone therapy compared with younger children. We also found that both diagnosis receipt and treatment initiation were more common among non-Hispanic white children and AFAB children relative to their respective counterparts. The observed differences by geographic locations require confirmation because of the limited sample size.

Taken together, these results indicate that, even in the presence of similar access to care, use and timing of services may differ across groups of GD children and adolescents. With respect to their clinical interpretation, our findings are more likely to inform primary health care providers who first encounter GD children rather than practitioners specializing in gender-affirming care. In future studies, researchers should explore the possible reasons for the observed differences by recruiting a cohort with a wider range of sociodemographic characteristics, especially with regards to race and ethnicity, and include data on parental perceptions of transgender care and pubertal staging. It would be interesting to know how many of the youth presenting to care for GAHT have already socially transitioned, as well as examine deeper the effect of therapy on psychological functioning. Perhaps the most important next step in this area of research is to compare health outcomes and quality of life among GD children and adolescents who began receiving care at different ages. These types of data are needed to inform clinical practice and facilitate development of evidence-based guidelines.

Drs Wagner and Goodman conceptualized the analysis plan and drafted and finalized the manuscript; Mr Panagiotakopoulos conceptualized the analysis plan, drafted and finalized the manuscript, provided clinical consultation in the interpretation of results, critically reviewed the manuscript for important intellectual content specific to transgender and gender-diverse youth and the end points of interest discussed in the manuscript, and revised the final version of the manuscript; Drs Bradlyn, Getahun, Roblin, and Silverberg conceptualized and designed the study and contributed to the acquisition of data, critically reviewed the manuscript for important intellectual content within areas of expertise, such as epidemiological methods, bias, health care access, and health service use interpretation, and broad messaging of the manuscript, and revised the final version of the manuscript; Dr Lash conceptualized and designed the study and contributed to the acquisition of data, critically reviewed the manuscript for important intellectual content within areas of expertise, such as epidemiological methods, bias, health care access, and health service use interpretation, and broad messaging of the manuscript, revised the final version of the manuscript, provided substantial analysis consultation and helped with interpretation of analyses, and critically reviewed and revised the manuscript for important statistical interpretation of the data; Ms Nash provided substantial analysis consultation and helped with interpretation of the analyses and critically reviewed and revised the manuscript for important statistical interpretation of the data; Dr Tangpricha provided clinical consultation in the interpretation of results, critically reviewed the manuscript for important intellectual content specific to transgender and gender-diverse youth at the end points of interest discussed in the manuscript, and revised the final version of the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

FUNDING: Funded by contract AD-12-11-4532 from the Patient-Centered Outcome Research Institute and grant R21HD076387 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Funded by the National Institutes of Health (NIH).

assigned female sex at birth

assigned male sex at birth

confidence interval

gender-affirming hormonal treatment

gender-diverse

gender dysphoria–related diagnosis

gonadotropin-releasing hormone

hazard ratio

Kaiser Permanente

Study of Transition, Outcomes, and Gender

World Professional Association for Transgender Health

Competing Interests

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Medical transition

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Puberty blockers potentially have a negative impact on neuropsychological functioning.

A 2024 review by Sallie Baxendale [1] extensively examined the neuropsychological impacts of puberty blockers. The review indicated that animal studies showed a non-reversible negative impact on cognitive and behavioral functions. In human studies, the evidence suggested detrimental effects on IQ among those treated with puberty blockers for precocious puberty. Specifically, one study documented an average decrease in full-scale IQ of 7 points, including a case where an individual’s IQ fell by 15 points from 138 to 123 after treatment. Another case study involving a gender dysphoric young person reported a drop of 9 points in global (overall) IQ and 15 points in working memory during the course of treatment with puberty blockers.

[1] Baxendale, S. (2024). The impact of suppressing puberty on neuropsychological function: A review. Acta Paediatrica, 113 (7), 1156-1167. [ Link ]

Puberty blockers are more than a ‘pause button’: roughly 98% of children who take them go on to take cross-sex hormones.

A 2021 study from the UK [1] found that only 1 out of 44 children placed on puberty blockers did not continue to take cross-sex hormones.

Similarly, a Dutch study [2] reported that only 1.9% of adolescents who started puberty suppression treatment abandoned this course and did not take cross-sex hormones.

In fact, in a different Dutch study [3] , “[n]o adolescent withdrew from puberty suppression, and all started cross‐sex hormone treatment, the first step of actual gender reassignment.”

Puberty blockers are drugs which change young bodies in ways we have yet to understand, and may be permanent. This is an experimental treatment program: puberty blockers have never been licensed to treat children with gender dysphoria, in any country.

[1] Carmichael, P., Butler, G., Masic, U., Cole, T. J., De Stavola, B. L., Davidson, S., Skageberg, E. M., Khadr, S., & Viner, R. M. (2021). Short-term outcomes of pubertal suppression in a selected cohort of 12 to 15 year old young people with persistent gender dysphoria in the UK. PLOS ONE 16 (2). [ Link ]

[2] Wiepjes, C.M., Nota, N.M., de Blok, C.J.M., Klaver, M., de Vries, A.L.C., Wensing-Kruger, S.A., de Jongh, R.T., Bouman, M.B., Steensma, T.D., Cohen-Kettenis, P., Gooren, L.J.G., Kreukels, B.P.C. & den Heijer, M. (2018). The Amsterdam Cohort of Gender Dysphoria Study (1972-2015): Trends in Prevalence, Treatment, and Regrets. Journal of Sexual Medicine 15 (4). [ Link ]

[3] de Vries, A.L.C., Steensma, T.D., Doreleijers, T.A. & Cohen-Kettenis, P.T. (2011). Puberty suppression in adolescents with gender identity disorder: a prospective follow-up study. J Sex Med 8 (8): 2276-83. [ Link ]

There has been a roughly twenty-fold rise in the number of people seeking transition, with teenagers hugely over-represented.

A 2017 paper [1] reports that “the prevalence of a self-reported transgender identity in children, adolescents and adults ranges from 0.5 to 1.3%, markedly higher than prevalence rates based on clinic-referred samples of adults.”

This is reflected in data from gender clinics. The UK’s Gender Identity Development Service reported [2] a twenty-fold increase in referrals over the course of the last decade:

This surge was primarily driven by adolescents, with 15 being the most common age of referral:

Similarly, a Dutch gender identity clinic reported [3] a twenty-fold increase, albeit over a longer time span: from 34 in 1980 to 686 in 2015:

New Zealand [4] , Finland [5] and Canada [6] have recorded similar dramatic exponential increases.

[1] Zucker, K. J. (2017). Epidemiology of gender dysphoria and transgender identity. Sexual Health 14 (5): 404-411. [ Link ]

[2] Gender Identity Development Service (2021). Referrals to GIDS, financial years 2010-11 to 2020-21. [Link]

[3] Wiepjes, C.M., Nota, N.M., de Blok, C.J.M., Klaver, M., de Vries, A.L.C., Wensing-Kruger, S.A., de Jongh, R.T., Bouman, M.B., Steensma, T.D., Cohen-Kettenis, P., Gooren, L.J.G., Kreukels, B.P.C. & den Heijer, M. (2018). The Amsterdam Cohort of Gender Dysphoria Study (1972-2015): Trends in Prevalence, Treatment, and Regrets. Journal of Sexual Medicine 15 (4). [ Link ]

[4] Delahunt, J.W., Denison, H.J., Sim, D.A., Bullock, J.J. & Krebs, J.D. (2018). Increasing rates of people identifying as transgender presenting to Endocrine Services in the Wellington region. N Z Med J 131: 33-42. [ Link ]

[5] Kaltiala-Heino, R., Sumia, M., Työläjärvi, M. & Lindberg, N. (2015). Two years of gender identity service for minors: overrepresentation of natal girls with severe problems in adolescent development. Child and Adolescent Psychiatry and Mental Health 9 (1). [ Link ]

[6] Aitken, M., Steensma, T.D., Blanchard, R., VanderLaan, D.P., Wood, H., Fuentes, A., Spegg, C., Wasserman, L., Ames, M., Fitzsimmons, C.L., Leef, J.H., Lishak, V., Reim, E., Takagi, A., Vinik, J., Wreford, J., Cohen-Kettenis, P.T., de Vries, A.L., Kreukels, B.P. & Zucker, K.J. (2015). Evidence for an altered sex ratio in clinic-referred adolescents with gender dysphoria. J Sex Med 12 (3): 756-63. [ Link ]

The profile of people seeking transition has shifted drastically, from overwhelmingly middle-aged males to predominantly adolescent females.

A 2017 paper [1] notes that “in adolescents, there has been a recent inversion in the sex ratio from one favouring birth-assigned males to one favouring birth-assigned females.” By contrast, over 90% of transsexual adults in the 1960s were male [2] .

In fact, there was hardly any scientific literature before 2012 on girls ages 11 to 21 ever having developed gender dysphoria at all. Yet of the young people described in Lisa Littman’s 2018 seminal paper on young people [3] , 82.8% were female.

The data for the UK’s Gender Identity Development Service [4] show that 138 children were referred in 2011, and most of those children were boys. By 2021, however, a complete sex ratio reversal had occurred, and the clinic saw 2383 children that year, with almost 70% being female.

A 2017 article by Lisa Marchiano [5] collated data from different clinics around the world and found international evidence for this shift in distribution.

[2] Barrett, J. (2015). Written evidence submitted by British Association of Gender Identity Specialists to the Transgender Equality Inquiry. data.parliament.uk [Link]

[3] Littman, L. (2018). Rapid-onset gender dysphoria in adolescents and young adults: A study of parental reports. PLOS ONE, 13 (8). [ Link ]

[4] Gender Identity Development Service (2021). Referrals to GIDS, financial years 2010-11 to 2020-21. [Link]

[5] Marchiano, L. (2017). Outbreak: On Transgender Teens and Psychic Epidemics. Psychological Perspectives 60 (3): 345-366. [Link]

There is limited evidence that medical transition leads to positive outcomes.

A number of different studies have noted the paucity of good quality evidence for transition.

An Australian paper [1] states that most available evidence indicating positive outcomes for gender reassignment is of poor quality.

A German study [2] “found insufficient evidence to determine the efficacy or safety of hormonal treatment approaches for transgender women in transition”, adding that “[t]his lack of studies shows a gap between current clinical practice and clinical research.”

A British review [3] conducted by the National Institute for Health and Care Excellence (NICE) graded certainty of evidence for puberty blocker use as “very low” in every category, including impact on gender dysphoria, mental health, body image, global functioning, psychosocial functioning, cognitive functioning, bone density and adverse effects.

A chapter [4] in an edited volume details the low evidence base for treatment pathways employed at the UK’s Gender Identity Development Service, demonstrating how negative evidence was “ignored or suppressed”.

Finally, a systematic review [5] commissioned by the World Professional Association for Transgender Health (WPATH) to “systematically review the effect of gender-affirming hormone therapy on psychological outcomes among transgender people” noted that, in some areas, there was low quality or insufficient evidence.

[1] D’Angelo, R. (2018). Psychiatry’s ethical involvement in gender-affirming care. Australasian Psychiatry 26 (5): 460-463. [ Link ]

[2] Haupt, C., Henke, M., Kutschmar, A., Hauser, B., Baldinger, S., Saenz, S.R. & Schreiber, G. (2020). Antiandrogen or estradiol treatment or both during hormone therapy in transitioning transgender women. Cochrane Database of Systematic Reviews 11. [ Link ]

[3] National Institute for Health and Care Excellence (2021). Evidence review: Gonadotrophin releasing hormone analogues for children and adolescents with gender dysphoria. National Institute for Health and Care Excellence (NICE); NHS England; NHS Improvement. [ Link ]

[4] Biggs, M. (2019). The Tavistock’s Experiment with Puberty Blockers. In: Moore, M. & Brunskell-Evans, H. (eds.). Inventing Transgender Children and Young People. Cambridge Scholars Publishing. [ Link ]

[5] Baker, K.E., Wilson, L.M., Sharma, R., Dukhanin, V., McArthur, K. & Robinson, K.A. (2021) Hormone Therapy, Mental Health, and Quality of Life Among Transgender People: A Systematic Review. Journal of the Endocrine Society 5 (4). [ Link ]

Studies on gender dysphoric young people often suffer from high rates of loss to follow-up – which could skew transition satisfaction rates.

In one study [1] of 77 pre-teen participants, 30% were lost to follow up by their teenage years: either they did not respond to the recruiting letter, or were not traceable. In another study [2] , as many as 75% of participants were lost to follow up.

An excellent précis of this problem can be found in a 2018 paper [3] , which gives further detail:

Smith et al. report that sex reassignment is effective, based on a study of 162 adults who had undergone SRS. They were able to obtain follow-up data from only 126 (78%) of subjects because a significant number were “untraceable” or had moved abroad.

De Cuypere et al. report that sex reassignment surgery is an effective treatment for transsexuals. Of 107 patients who had undergone SRS between 1986 and 2001, 30 (28%) could not be contacted and 15 (14%) refused to participate.

Johannson et al. reported good outcomes for SRS. Of 60 patients who had undergone SRS, 42 (70%) agreed to participate in the follow up research. Of the non-participants, 1 had died of complications of SRS, 8 could not be contacted and 9 refused to participate.

Salvador et al. reported that SRS has a positive effect on psychosocial functioning. Only 55 of the 69 patients (80%) could be contacted as 17 were lost to follow-up

Van de Grift et al. reported 94–96% of patients are satisfied with SRS and have good quality of life. A total of 546 patients with Gender Dysphoria who had applied for SRS at clinics in Amsterdam, Hamburg and Ghent were contacted to complete an online survey. Only 201 (37%) responded and completed the survey. 

A good example of how this phenomenon can affect satisfaction and regret statistics comes from a 2018 paper [4] , which is often cited as proof of low regret rates. The loss to follow up rate in this paper is 36%. The authors also state:

In addition, in our population the average time to regret was 130 months, so it might be too early to examine regret rates in people who started with HT [hormonal treatment] in the past 10 years.

[1] Wallien, M.S. & Cohen-Kettenis P.T. (2008) Psychosexual outcome of gender-dysphoric children. J Am Acad Child Adolesc Psychiatry 47 (12): 1413-23. [ Link ]

[2] Rauchfleisch, U., Barth, D. & Battegay, R. (1998). Resultate einer Langzeitkatamnese von Transsexuellen. Der Nervenzart 69: 799-805. [ Link ]

[3] D’Angelo, R. (2018). Psychiatry’s ethical involvement in gender-affirming care. Australasian Psychiatry 26 (5): 460-463. [ Link ]

[4] Wiepjes, C.M., Nota, N.M., de Blok, C.J.M., Klaver, M., de Vries, A.L.C., Wensing-Kruger, S.A., de Jongh, R.T., Bouman, M.B., Steensma, T.D., Cohen-Kettenis, P., Gooren, L.J.G., Kreukels, B.P.C. & den Heijer, M. (2018). The Amsterdam Cohort of Gender Dysphoria Study (1972-2015): Trends in Prevalence, Treatment, and Regrets. Journal of Sexual Medicine 15 (4). [ Link ]

There is evidence that all-cause mortality is higher among trans people than among the general population.

A Swedish study [1] found that sex-reassigned transsexual persons – both male and female – had approximately a three times higher risk of all-cause mortality than non-transsexuals. Elevated causes of mortality included cancer, cardiovascular disease, and violent crime:

This finding was backed up by a Dutch study [2] , which stated:

This observational study showed an increased mortality risk in transgender people using hormone treatment, regardless of treatment type. This increased mortality risk did not decrease over time.

[1] Dhejne, C., Lichtenstein, P., Boman, M., Johansson, A. L. V., Långström, N., & Landén, M. (2011). Long-term follow-up of transsexual persons undergoing sex reassignment surgery: Cohort study in Sweden. PLoS ONE, 6(2). [ Link ]

[2] de Blok, C.J.M., Wiepjes, C.M., van Velzen, D.M., Staphorsius, A.S., Nota, N.M., Gooren, L.J.G., Kreukels, B.P.C. & den Heijer, M. (2021). Mortality trends over five decades in adult transgender people receiving hormone treatment: a report from the Amsterdam cohort of gender dysphoria. The Lancet Diabetes & Endocrinology 9. [ Link ]

There is little evidence that medical transition decreases suicidality.

When it comes to gender dysphoric children, there is little evidence that medical transition decreases suicide rates. There is little evidence to assert that puberty blockers are necessary to prevent suicide [1] .

After sex reassignment surgery, one study showed that adult transsexual clients were 4.9 times more likely to have made a suicide attempt and 19.1 times more likely to have died from suicide, after adjusting for prior psychiatric comorbidity [2] . Similarly, an Australian paper [3] notes that many patients have poor outcomes, which puts them at risk of suicide.

A prominent study [4] claiming that medical transition alleviated suicidality had to be corrected [5] , to clarify that it proved “no advantage of surgery” in this regard.

A long-term Swedish study [6] finds that post-operative transgender people have “considerably higher risks” for suicidal behavior.

Similarly, a study in the European Journal of Endocrinology [7] demonstrates that suicide rates among transgender male-to-females were 51% higher than the general population.

[1] Biggs, M. (2020). Puberty Blockers and Suicidality in Adolescents Suffering from Gender Dysphoria. Archives of Sexual Behavior (49): 2227–2229. [ Link ]

[2] Zucker, K.J., Lawrence, A.A., Kreukels, B.P. (2016). Gender Dysphoria in Adults. Annu Rev Clin Psychol. 12: 217-47. [ Link ]

[4] Bränström, R. & Pachankis, J. E. (2019). Reduction in Mental Health Treatment Utilization Among Transgender Individuals After Gender-Affirming Surgeries: A Total Population Study. American Journal of Psychiatry 177 (8): 727-734. [ Link ]

[5] American Journal of Psychiatry (2020). Correction to Bränström and Pachankis. Published online: 1 August 2020. [ Link ]

[6] Dhejne, C., Lichtenstein, P., Boman, M., Johansson, A. L. V., Långström, N., & Landén, M. (2011). ‘Long-term follow-up of transsexual persons undergoing sex reassignment surgery: Cohort study in Sweden’. PLoS ONE, 6(2). [ Link ]

[7] Asscheman, H., Giltay, E. J., Megens, J. A. J., de Ronde, W., van Trotsenburg, M. A. A. & Gooren, L. J. G. (2011). A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. European Journal of Endocrinology 164 (4). [ Link ]

Female-to-male genital reconstruction surgery has a high negative outcome rate, including urethral compromise and worsened mental health.

The results of a 2021 international survey [1] of 129 female-to-male patients who underwent genital reconstruction surgery support anecdotal reports that complication rates following genital reconstruction are higher than are commonly reported in the surgical literature. 

Complication rates, including urethral compromise, and worsened mental health outcomes remain high for gender affirming penile reconstruction. In total, the 129 patients reported 281 complications requiring 142 revisions.

Another paper [2] found a 70% complication rate in one type of female-to-male genital reconstruction surgery.

Even with the “radial forearm free flap” method of creating a synthetic penis — “considered by many as the gold standard for phalloplasty” [3] — there are high rates of complications, with up to 64% urethroplasty related complications [4] .

[1] Robinson, I.S., Blasdel, G., Cohen, O., Zhao, L.C. & Bluebond-Langner, R. (2021). Surgical Outcomes Following Gender Affirming Penile Reconstruction: Patient-Reported Outcomes From a Multi-Center, International Survey of 129 Transmasculine Patients. J Sex Med 18 (4): 800-811. [ Link ]

[2] Bettocchi, C., Ralph, D.J. & Pryor, J.P. (2005). Pedicled pubic phalloplasty in females with gender dysphoria. BJU Int. 95:120–4. [ Link ]

[3] Rashid, M. & Tamimy, M. S. (2013). Phalloplasty: The dream and the reality. Indian J Plast Surg 46 (2): 283-293. [Link]

[4] Fang, R.H., Lin, J.T. & Ma S. (1994). Phalloplasty for female transsexuals with sensate free forearm flap. Microsurgery 15: 349–52. [ Link ]

The chances of developing osteoporosis and cardiovascular problems increase with feminizing hormones.

A 2012 paper [1] found that a quarter of the male-to-female transsexuals it studied had osteoporosis at the lumbar spine and radius.

In the same study, 6% of male-to-female transsexuals experienced a thromboembolic event (a blood clot causing obstruction), and another 6% experienced other cardiovascular problems. These effects were observed after only 11.3 years of hormone treatment on average.

A further study [2] found that long-term bone mineral density decreases in transwomen who take cross-sex hormones in the long term.

[1] Wierckx, K., Mueller, S., Weyers, S., Van Caenegem, E., Roef, G., Heylens, G. & T’Sjoen, G. (2012). Long-Term Evaluation of Cross-Sex Hormone Treatment in Transsexual Persons. The Journal of Sexual Medicine 9 (10): 2641-2651. [Link]

[2] Delgado-Ruiz, R., Swanson, P., & Romanos, G. (2019). Systematic Review of the Long-Term Effects of Transgender Hormone Therapy on Bone Markers and Bone Mineral Density and Their Potential Effects in Implant Therapy. Journal of clinical medicine 8 (6): 784. [ Link ]

Puberty blockers and cross-sex hormones negatively impact bone health in a significant number of cases.

There is little long-term evidence on bone mass density in relation to puberty blockers. However, in a significant minority of cases of long-term puberty suppression related to gender identity, bone mass density scores qualify as “low for age” [1] . Low bone mass density increases risk of osteoporosis and fractures.

Adolescents who enter puberty at an older age have persistently lower bone mass density than their peers [2] : in one case study [3] , an adolescent had a bone mass density -2 standard deviations below the mean after three years of blocking puberty.

It has also been noted [4] that:

In early-pubertal transgender youth, BMD [bone mass density] was lower than reference standards for sex designated at birth. This lower BMD may be explained, in part, by suboptimal calcium intake and decreased physical activity–potential targets for intervention.

Bone metabolism is also decreased as a result of taking cross-sex hormones, for both males and (in later life) females [5] .

[1] Biggs, M. (2021). Revisiting the effect of GnRH analogue treatment on bone mineral density in young adolescents with gender dysphoria. Journal of Pediatric Endocrinology and Metabolism 34 (7): 937-939. [ Link ]

[2] Elhakeem, A., Frysz, M., Tilling, K., Tobias, J.H. & Lawlor, D.A. (2019). Association Between Age at Puberty and Bone Accrual From 10 to 25 Years of Age. JAMA Netw Open; 2(8). [ Link ]

[3] Pang, K.C., Notini, L., McDougall, R., Gillam, L., Savulescu, J., Wilkinson, D., Clark, B.A., Olson-Kennedy, J., Telfer, M.M. & Lantos, J.D. (2020). Long-term Puberty Suppression for a Nonbinary Teenager. Pediatrics 145 (2). [ Link ]

[4] Lee, J. Y., Finlayson, C., Olson-Kennedy, J., Garofalo, R., Chan, Y. M., Glidden, D. V., & Rosenthal, S. M. (2020). Low Bone Mineral Density in Early Pubertal Transgender/Gender Diverse Youth: Findings From the Trans Youth Care Study. Journal of the Endocrine Society 4 (9). [ Link ]

[5] Vlot, M.C., Wiepjes, C.M., de Jongh, R.T., T’Sjoen, G., Heijboer, A.C. & den Heijer, M. (2019). Gender-Affirming Hormone Treatment Decreases Bone Turnover in Transwomen and Older Transmen. J Bone Miner Res, 34: 1862-1872. [ Link ]

In one well-known study, the psychological state of some gender dysphoric children receiving puberty blockers deteriorated.

A British study conducted in 2021 by Carmichael et al.   [1]  evaluated the effects of puberty blockers on children aged 12 to 15 with severe and persistent gender dysphoria. The study concluded that these treatments did not significantly affect the children’s psychological function, thoughts of self-harm, or body image, although they did experience decreased growth in height and bone strength by the end of their treatment at age 16.

However, a crucial re-analysis by McPherson and Freedman in 2023 [2] re-examined the original findings by assessing individual trajectories rather than group averages. This analysis showed that after 12 months on puberty blockers, 34% of the children experienced a deterioration in psychological state, 29% improved, and 37% remained unchanged. This discredits the initial study’s conclusion of “no significant change” in psychological function.

[2] McPherson, S., & Freedman, D. E. (2023). Psychological Outcomes of 12–15-Year-Olds with Gender Dysphoria Receiving Pubertal Suppression in the UK: Assessing Reliable and Clinically Significant Change.  Journal of Sex & Marital Therapy , 1-11. [ Link ]

Medical transition puts both males and females at risk of infertility.

A wide-ranging study [1] found that gender-related drug regimens place patients at risk of infertility:

Suppression of puberty with gonadotropin-releasing hormone agonist analogs (GnRHa) in the pediatric transgender patient can pause the maturation of germ cells, and thus, affect fertility potential. Testosterone therapy in transgender men can suppress ovulation and alter ovarian histology, while estrogen therapy in transgender women can lead to impaired spermatogenesis and testicular atrophy. The effect of hormone therapy on fertility is potentially reversible, but the extent is unclear.

On surgeries, the study noted that cross-sex surgery that includes hysterectomy and oophorectomy in transmen or orchiectomy in transwomen results in permanent sterility.

[1] Cheng, P.J., Pastuszak, A.W., Myers, J.B., Goodwin, I.A. & Hotaling, J.M. (2019). Fertility concerns of the transgender patient. Transl Androl Urol. 8 (3): 209-218. [ Link ]

Long-term testosterone use in natal females can cause vaginal atrophy, which makes sex painful.

A study [1] of 16 female-to-male transgender individuals concluded that long-term testosterone administration leads to vaginal atrophy (Baldassarre et al., 2013). The study noted that:

Vaginal samples from FtM showed a loss of normal architecture of the epithelium, intermediate and superficial layers were completely lost, and glycogen content was depleted.

Vaginal atrophy, characterized by thinning of vaginal walls and poor lubrication of vaginal tissues, leads to tearing, micro abrasions, bleeding, and painful intercourse.

[1] Baldassarre, M., Giannone, F., Foschini, M., Battaglia, C., Busacchi, P., Venturoli, S., & Meriggiola, M. (2013). Effects of long-term high dose testosterone administration on vaginal epithelium structure and estrogen receptor-α and -β expression of young women. International Journal Of Impotence Research, 25 (5): 172-177. [ Link ]

In one study, 11% of transmen who took testosterone developed a condition called erythrocytosis, which impacts red blood cells and slows the blood flow.

A study [1] of 776 transmen who took testosterone demonstrated that 11% of them developed erythrocytosis, a condition which slows the blood flow, and can lead to headaches, confusion, high blood pressure, nosebleeds, blurred vision, itching and fatigue.

[1] Madsen, M.C., van Dijk, D. Wiepjes, C.M., Conemans, E.B., Thijs, A. & den Heijer, M. (2021). Erythrocytosis in a Large Cohort of Trans Men Using Testosterone: A Long-Term Follow-Up Study on Prevalence, Determinants, and Exposure Years. The Journal of Clinical Endocrinology & Metabolism 106 (6): 1710–1717. [ Link ]

Genital surgeries tend to reduce the capacity for orgasm in males, and may do so in females.

One study showed that around 30% of male-to-female genital surgeries result in the inability to orgasm [1] .

Figures on female-to-male transitioners are less clear. However, a clinical follow-up study [2] of 38 transmen – 29 of whom had received phalloplasty, and 9 metoidioplasty – found that reported loss of orgasmic capacity was more marginally common than reported gain of orgasmic capacity.

The negative intrapsychic and interpersonal consequences of anorgasmia (the inability to climax) is well-documented, and applies equally to transgender individuals [3] .

[1] Manrique, O., Adabi, K., Martinez-Jorge, J., Ciudad, P., Nicoli, F. and Kiranantawat, K. (2018). Complications and Patient-Reported Outcomes in Male-to-Female Vaginoplasty—Where We Are Today. Annals of Plastic Surgery 80 (6): 684-691. [ Link ]

[2] van de Grift, T., Pigot, G., Kreukels, B., Bouman, M., & Mullender, M. (2019). Transmen’s Experienced Sexuality and Genital Gender-Affirming Surgery: Findings From a Clinical Follow-Up Study. Journal Of Sex & Marital Therapy 45 (3): 201-205. [ Link ]

[3] Levine, S. (2018). Informed Consent for Transgendered Patients. Journal Of Sex & Marital Therapy, 45(3), 218-229. [ Link ]

Feminizing hormones reduce sexual function in males.

Feminizing hormonal treatments lead to a lessening drive, erectile dysfunction, and shrinking of testes and penis [1] , significantly compromising sexual function.

A Belgian doctoral thesis study [2] found that 69.7% of transwomen reported a decrease in sexual desire — while the opposite effect is found in transmen.

[1] Levine, S. (2018). Informed Consent for Transgendered Patients. Journal Of Sex & Marital Therapy, 45(3), 218-229. [ Link ]

[2] Elaut, E. (2014). Biopsychosocial factors in the sexual desire of contraception‐using couples and trans persons. Doctoral thesis, University of Ghent. [ Link ]

Vaginoplasty can result in fistula, stenosis, necrosis, prolapse and even death.

Male-to-female genital surgery (vaginoplasty) is associated with significant long-term complications: there is a 2% risk of fistula, 14% risk of stenosis (abnormal narrowing), 1% risk of necrosis (tissue death) and 4% risk of prolapse [1] .

One systematic review [2] found an overall complication rate of 32.5%.

A Dutch study [3] of 55 (out of an original 70) adolescents treated with puberty blockers, cross sex hormones, and genital surgery, showed that among 22 male-to-female patients who underwent vaginoplasty, one adolescent died as a result of necrotizing fasciitis after the surgery.

[2] Dreher, P.C., Edwards, D., Hager, S., Dennis, M., Belkoff, A., Mora, J., Tarry, S. & Rumer, K.L. (2018). Complications of the neovagina in male-to-female transgender surgery: A systematic review and meta-analysis with discussion of management. Clin Anat. 31 (2):191-199. [ Link ]

[3] de Vries, A., McGuire, T., Steensma, E., Wagenaar, T., Doreleijers, P. & Cohen-Kettenis, P. (2014). Young adult psychological outcome after puberty suppression and gender reassignment . [ Link ]

Around 1 in 5 vaginoplasty surgeries lead to corrective surgery.

A systematic review [1] of neo-vagina surgeries found a re-operation rate of 21.7% for non-esthetic reasons.

A Brazilian paper [2] found a somewhat lower, but similar, reoperation rate of 16.8%.

[1] Dreher, P.C., Edwards, D., Hager, S., Dennis, M., Belkoff, A., Mora, J., Tarry, S. & Rumer, K.L. (2018). Complications of the neovagina in male-to-female transgender surgery: A systematic review and meta-analysis with discussion of management. Clin Anat. 31 (2):191-199. [ Link ]

[2] Moisés da Silva, G.V., Lobato, M.I.R., Silva, D.C., Schwarz, K., Fontanari, A.M.V., Costa, A.B., Tavares, P.M., Gorgen, A.R.H., Cabral, R.D. & Rosito, T.E. (2021). Male-to-Female Gender-Affirming Surgery: 20-Year Review of Technique and Surgical Results. Frontiers in Surgery 8. [ Link ]

There is evidence that up to a quarter of transgender genital surgeries result in incontinence.

A systematic literature review [1] found that 21% of male-to-female patients and 25% of female-to-male patients suffered from incontinence as a result of transgender genital surgery.

One recent study [2] estimates the number of post-operative transsexuals suffering stress incontinence to be 23%. This study was not a literature review, and almost all of the participants were male-to-female.

[1] Nassiri, N., Maas, M., Basin, M., Cacciamani, G.E. & Doumanian, L.R. (2020). Urethral complications after gender reassignment surgery: a systematic review. Int J Impot Res. [ Link ]

[2] Kuhn, A., Santi, A. & Birkhäuser, M. (2011). Vaginal prolapse, pelvic floor function, and related symptoms 16 years after sex reassignment surgery in transsexuals. Fertil Steril. 95: 2379-82. [ Link ]

Medical transition reduces dating pool size and likelihood of marriage.

Individuals undergoing biomedical interventions to address their gender dysphoria are at risk for having a greatly diminished pool of individuals who are willing to sustain an intimate physical and loving relationship [1] .

This is evidenced in the much lower marriage rates of transgender adults [2] .

[2] Yarbrough, E. (2018). Transgender mental health. Washington, DC: American Psychiatric Association Publishing. [ Link ]

There is evidence that it is harder to sustain meaningful sexual relationships after medical transition.

A study [1] on informed consent found that male-to-female transitioners who are attracted to men may discover that men who are sexually interested in them are specifically interested in their trans status, and have no interest in serious long-term relationships. 

The same study noted that male-to-female transitioners who are attracted to women may find that lesbians are unwilling to engage in a sexual relationship with a male.

Because most female-to-male transitioners do not undergo phalloplasty, their ability to attract desirable sexual partners, and sustain relationships with them, could be compromised.

Only a single case [2] of a female-to-male transitioner treated with puberty blockers followed by cross-sex hormones and surgeries has feen followed long-term.

The individual, who was in his thirties during the follow up, reported an inability to have a satisfying sexual life due to “shame about his genital appearance and his feelings of inadequacy in sexual matters”. The researchers concluded, that despite the gender reassignment, “in the area of intimate relationships, it may remain difficult to find a suitable partner”.

[2] Cohen-Kettenis, P., Schagen, S., Steensma, T., de Vries, A., & Delemarre-van de Waal, H. (2011). Puberty Suppression in a Gender-Dysphoric Adolescent: A 22-Year Follow-Up. Archives Of Sexual Behavior 40 (4): 843-847. [ Link ]

Transmen are four or five times more likely than females in general to suffer a heart attack.

A 2019 study [1] found that post-operative female-to-male transgender people were 4.9 times as likely to suffer a myocardial infarction (heart attack) than women in general.

Another study [2] also found a somewhat smaller yet still large discrepancy, concluding that transmen were 3.69 more likely to suffer a heart attack than women in general.

[1] Alzahrani, T. Nguyen, T., Ryan, A., Dwairy, A. McCaffrey, J., Yunus, R., Forgione, J., Krepp, J., Nagy, C., Mazhari, R. & Reiner, J. (2019). Cardiovascular Disease Risk Factors and Myocardial Infarction in the Transgender Population. Circulation: Cardiovascular Quality and Outcomes 12 (4). [ Link ]

[2] Nota, N.M., Wiepjes, C.M., de Blok, C.J.M., Gooren, L.J.G., Kreukels, B.P.D. & den Heijer, M. (2019). Occurrence of Acute Cardiovascular Events in Transgender Individuals Receiving Hormone Therapy: Results From a Large Cohort Study. Circulation 139: 1461-1462. [ Link ]

In one study of detransitioners, around half were worried about the medical complications of transitioning.

A study [1] of 100 detransitioners showed that 49% had concerns about potential medical complications from transitioning. 

A second study [2] of detransitioners and desisters – most of whom were detransitioners who had undergone medical transition – arrived at a higher figure, with 62% citing health concerns as a motivating factor for detransition.

[1] Littman, L. (2021). Individuals Treated for Gender Dysphoria with Medical and/or Surgical Transition Who Subsequently Detransitioned: A Survey of 100 Detransitioners. Arch Sex Behav. [ Link ]

[2] Vandenbussche, E. (2021). Detransition-Related Needs and Support: A Cross-Sectional Online Survey. Journal of Homosexuality. [ Link ]

In one study of detransitioners, around half believed that they received inadequate care.

The majority (55.0%) of detransitioners in a 100-participant study [1] felt that they did not receive an adequate evaluation from a doctor or mental health professional before starting transition.

A second study [2] of detransitioners and desisters – most of whom were detransitioners who had undergone medical transition – arrived at a similar, although slightly lower, figure, with 45% of detransitioners not feeling properly informed about the health implications of the accessed treatments and interventions before undergoing them.

Strength advantage over females is retained by male-to-female transitioners (transwomen).

A systematic review of 24 studies concluded that while male-female transitioners  (transwomen)  do experience  some  decrease in muscle mass; values for strength and muscle area in transwomen remain above those of biological women, even after 36 months of hormone therapy. [1,2] .

Figure one [1] :

A systematic review of 24 studies concluded that while male-female transitioners (trans women) do experience a decrease in muscle mass; values for strength and muscle area in transwomen remain above those of biological women, even after 36 months of hormone therapy. [2]

[1] Hilton, E. N. & Lundberg, T.R. (2021). Transgender Women in the Female Category of Sport: Perspectives on Testosterone Suppression and Performance Advantage. Sports Med 51: 199–214. [ Link]

[2] Harper J, O’Donnell E, Sorouri Khorashad B , et al . (2021). How does hormone transition in transgender women change body composition, muscle strength and haemoglobin? Systematic review with a focus on the implications for sport participation. British Journal of Sports Medicine  ; 55: 865-872. [Link]

One year of cross sex hormone therapy causes robust increases in muscle mass and strength in transmen (females) but modest changes in transwomen (males).

Thigh muscle volume increased 15% in transmen, which was paralleled by increased quadriceps cross-sectional area (CSA) (15%) and radiological density 6%. In transwomen, the corresponding parameters decreased by –5% (muscle volume) and –4% (CSA), while density remained unaltered. The transmen increased strength over the assessment period, while the transwomen generally maintained their strength levels [1] :

[1] Wiik, A., Lundberg, T. R., Rullman, E., Andersson, D. P., Holmberg, et al. (2019). Muscle strength, size, and composition following 12 months of gender-affirming treatment in transgender individuals. The Journal of Clinical Endocrinology & Metabolism , 105 (3). [Link]

Long term testosterone use potentially compromises fertility and negatively affects ovarian follicle health.

One study in 2023 found that long-term testosterone exposure, as seen in transgender men undergoing gender-affirming therapy, could potentially compromise fertility by negatively affecting ovarian follicle growth, health, and DNA integrity.

In 2023, a study by Bailie et al. [1] explored the effects of long-term testosterone exposure on ovarian follicles in transgender men receiving gender-affirming endocrine therapy. The research indicated that testosterone was linked with decreased follicle growth activation, poor follicle health, and increased DNA damage, suggesting possible impacts on fertility. Further, these negative effects were intensified following six days of in vitro culture. These findings may have crucial implications for reproductive health and fertility considerations among transgender men receiving testosterone as part of their gender-affirming therapy.

Bailie, E., Maidarti, M., Hawthorn, R., Jack, S., Watson, N., Telfer, E. E., & Anderson, R. A. (2023). The ovaries of transgender men indicate effects of high dose testosterone on the primordial and early growing follicle pool.  Reproduction and Fertility , 4(2). [Link]

Evidence suggests that treatments used to feminize transwomen result in altered brain structures.

One study showed that estradiol valerate and cyproterone acetate, treatments used to feminize adult male rats mirroring those in transwomen, resulted in altered brain structure, including reduced volume and elevated specific metabolites. 

In a 2020 study [1] , Goémez et al. used a rat model to investigate the effects of feminizing hormonal treatments, specifically estradiol valerate and cyproterone acetate, akin to those given to transwomen. They monitored changes over 30 days using structural MRI and Diffusion Tensor Imaging. The researchers found that these treatments led to a generalized bilateral decrease in cortical volume. Additionally, they noted increases in the relative concentration of brain metabolites, including glutamate and glutamine. The study concludes that these hormonal treatments induce significant changes in brain structure and metabolite concentration. 

[1] Gómez, Á., Cerdán, S., Pérez-Laso, C., Ortega, E., Pásaro, E., Fernández, R., … & Guillamon, A. (2020). Effects of adult male rat feminization treatments on brain morphology and metabolomic profile.  Hormones and behavior ,  125 , 104839.  [Link]

Long-term testosterone use in females may induce early menopause, leading to pelvic dysfunction, increased mortality risk and many other challenges.

A 2024 study by da Silva et al. [1] found that 94.1% of 68 trans-identified females using testosterone experienced pelvic dysfunctions typically seen in postmenopausal women, including urinary (86.7%), sexual (52.9%), and bowel (45.6%) problems. These symptoms appeared as early as age 18, with an average onset age of 28.

This early onset of menopausal-like symptoms is particularly concerning given findings from another 2024 study by Haapakoski et al. [2] , which demonstrated increased mortality risks associated with early menopause. The study found that women experiencing early menopause (n=5,800) were twice as likely to die from heart disease and four times more likely to die from cancer compared to those with typical menopause onset (n=23,000).

Testosterone use may induce early menopause by inhibiting ovarian function [3] and decreasing estrogen production in the body [4] .

[1] da Silva, L. M. B., Freire, S. N. D., Moretti, E., & Barbosa, L. (2024). Pelvic Floor Dysfunction in Transgender Men on Gender-affirming Hormone Therapy: A Descriptive Cross-sectional Study.  International Urogynecology Journal , 1-8. [ Link ]

[2] Haapakoski, H., Silven, H., Pesonen, P., Savukoski, S., & Niinimaki, M. (2024, May). Mortality among women with POI, nationwide register based case-control study. In  Endocrine Abstracts  (Vol. 99). Bioscientifica. [ Link ]

[3] Bailie, E., Maidarti, M., Hawthorn, R., Jack, S., Watson, N., Telfer, E. E., & Anderson, R. A. (2023). The ovaries of transgender men indicate effects of high dose testosterone on the primordial and early growing follicle pool.  Reproduction and Fertility , 4(2). [ Link ] [4] Chan, K. J., Jolly, D., Liang, J. J., Weinand, J. D., & Safer, J. D. (2018). Estrogen levels do not rise with testosterone treatment for transgender men. Endocrine Practice, 24(4), 329-333. [ Link ]

People who have undergone cross-sex surgery exhibit a significantly higher suicide risk.

Dhejne et al. (2011) [1] conducted the longest follow-up study to date on the outcomes of “sex reassignment surgery”, covering a period of 30 years (1973-2003) and involving 324 individuals in Sweden. The study compared these individuals to matched controls based on birth year and sex, revealing that those who had undergone surgery exhibited a significantly increased suicide risk, with rates nearly 19.1 times higher than their matched controls.

In the US, a 2024 study by Straub et al. [2] analyzed the psychiatric risks of those who’ve undergone “gender-affirmation surgery” using a large patient dataset. This study compared individuals who had undergone the surgery to two control groups: one consisting of adults who had emergency department visits without any surgery and another comprising individuals who underwent either a tubal ligation or vasectomy. The findings indicated that those who had “gender-affirmation surgery” faced a 12.12-fold increased risk of attempting suicide compared to the emergency visit control group, and a 4.71-fold higher risk compared to the tubal ligation/vasectomy control group.

[1] Dhejne, C., Lichtenstein, P., Boman, M., Johansson, A. L., Långström, N., & Landén, M. (2011). Long-term follow-up of transsexual persons undergoing sex reassignment surgery: cohort study in Sweden.  PloS one ,  6 (2), e16885. [ Link ]

[2] Straub, J. J., Paul, K. K., Bothwell, L. G., Deshazo, S. J., Golovko, G., Miller, M. S., & Jehle, D. V. (2024). Risk of suicide and self-harm following gender-affirmation surgery.  Cureus ,  16 (4). [ Link ]

There is no high-quality evidence supporting the use of puberty blockers for gender distress.

A 2024 systematic review by Taylor et al. at the University of York [1] was commissioned by the Cass Review to rigorously assess the safety and effectiveness of puberty suppression in adolescents with gender dysphoria. Analyzing studies up to April 2022, the review included 11 cohort, 8 cross-sectional, and 31 pre-post studies, but only one cross-sectional study met high-quality standards. The meta-analysis of moderate to high-quality studies showed limited and inconsistent evidence of benefits in areas like gender dysphoria, mental health, and body satisfaction.

This finding aligns with the previous 2020 review by the British National Institute for Clinical Excellence (NICE) on puberty blockers [2] , which described the supporting evidence as “very low” quality. The review noted minimal changes in key outcomes like gender dysphoria, mental health, and quality of life due to small, uncontrolled observational studies. Furthermore, a 2024 review from Germany by Zepf et al. [3] , adhering to NICE criteria, confirmed the absence of new studies on puberty blockers for gender dysphoria since the NICE review.

[1] Taylor, J., Mitchell, A., Hall, R., Heathcote, C., Langton, T., Fraser, L., & Hewitt, C. E. (2024). Interventions to suppress puberty in adolescents experiencing gender dysphoria or incongruence: a systematic review.  Archives of disease in childhood , archdischild-2023-326669. [ Link ] 

[2] National Institute for Health and Care Excellence (2021). Evidence review: Gonadotrophin releasing hormone analogues for children and adolescents with gender dysphoria. National Institute for Health and Care Excellence (NICE); NHS England; NHS Improvement. [ Link ]

[3] Zepf, F. D., König, L., Kaiser, A., Ligges, C., Ligges, M., Roessner, V., … & Holtmann, M. (2024). Beyond NICE: Aktualisierte systematische Übersicht zur Evidenzlage der Pubertätsblockade und Hormongabe bei Minderjährigen mit Geschlechtsdysphorie.  Zeitschrift für Kinder-und Jugendpsychiatrie und Psychotherapie . [ Link ]

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How Often Do People Regret Transitioning?

It’s a complex question, but we do have some data..

An opinion piece recently came out in the New York Times looking at the ongoing debate on transgender youth. If you’ve read the piece, you might be forgiven for thinking that huge swaths of children are receiving surgery for gender dysphoria, and that many or even most of them regret their transitions. “I realized that I had lived a lie for over five years,” one destransitioning teen told the Times . Members of the trans community who track legislation and critique media coverage called the piece misleading , and even suggested it followed the “ climate denier playbook .”

Now, I have no particular stake here. I’m not trans, I don’t work in that area of health care, and I’m a cis man. I am, however, an epidemiologist, and I spend a lot of my time checking scientific facts that are online with the goal of helping people better understand health, science, and how the media covers those things. In this case, one key question arose from the New York Times piece that author Pamela Paul did not really answer: What proportion of people who access medical care to transition genders regret doing so?

You might answer, “Why does anyone care?,” which is, to be honest, not unreasonable . Some proportion of people experience regret for any medical procedure, from chemotherapy to orthopedic surgery. Nonetheless, we don’t see op-eds about the awful risks of hip replacements. It’s inevitable that some percentage of teens who transition will regret it; the real question is whether the medical care is beneficial on the whole—not whether the occasional person later regrets a medical choice they made in their youth.

It’s also important to note that we don’t really care about the crude number of people who regret transition, we care about the rate . If more people choose to transition, then more people, in total, will regret it. If the number of people transitioning goes from (to use arbitrary numbers) 1,000 to 100,000, but the number of people regretting it goes from 50 to 100, then the rate has dropped massively and it’s a very good thing, even though the crude number has doubled.

A good place to start when looking at the rate of regret for people transitioning in modern medical settings is to think about the upper and lower bounds. The highest estimate that I’ve come across is this recent study of people using the U.S. military health care system. It doesn’t deal with regret head-on, though. The authors looked at transgender or gender-diverse people who were using their parent’s or spouse’s military health care to access hormones for gender-related care, and looked at how many of them stopped getting these drugs over a four-year period. At the end of the study, about 30 percent of the people who started accessing hormones through this system stopped, with a lower rate for kids and higher rate for adults. (They may have gone elsewhere for hormones, though.)

The lowest estimate I’ve seen for regret after gender-related care is based primarily on people who have had gender-affirming surgery. A recent systematic review and meta-analysis —a type of study where the authors aggregate lots of papers into one big estimate—that combined such studies found an overall rate of 1 percent for regret after surgery for both transmasculine and transfeminine surgeries. This echoes other large cohorts which have found that only a tiny proportion of the people who have these surgeries eventually report regretting the procedure.

The issue here is that neither of these extremes are reliable estimates of regret. The 30 percent figure obviously does not map onto regret. Many people stop using their parent or partner’s health care for reasons completely unrelated to transition regret (i.e., divorce). And the studies of surgery in the review are mostly surgeons following up with their own patients, with quite high dropout rates. It’s not surprising that only 1 percent of people report to a surgeon who did an operation that they regret it!

There’s also a problem here about how we define “regret.” One of the biggest studies on transition-related regret was on the Amsterdam gender clinic , including nearly 7,000 people over 43 years. These authors defined “regret” as a patient who came back to the clinic after surgery to access hormones that would reverse their gender transition (and who had this noted in their records). By this definition, less than 1 percent of people regretted their surgery. But this is obviously not a particularly useful definition, because it will miss all of the people who regretted their procedures but went elsewhere for their follow-up care, or simply never got back to the original clinic about their regret.

Perhaps the most useful way to examine regret is to look at the proportion of people who cease their transition and go back to the gender they were originally. A large national study found that 13.1 percent of transgender people participating in the U.S. Transgender Survey reported detransitioning at some point in their lives. I think that’s a fairly reasonable estimate of the rate of people experiencing some measure of regret around their transition experience.

The authors of this study are careful to argue that the 13.1 percent figure isn’t a measure of regret, saying that “these experiences did not necessarily reflect regret regarding past gender affirmation.” Most of them reported that external factors were behind their detransition—a common reason was “pressure from a parent”—and all of them still identified as trans when they took part in the survey.

However, I think that the figure in that study is useful for precisely the reasons discussed in the study itself: Neither detransition nor regret are simple concepts. Transition, as with all social phenomena, is complex. You can stop taking hormones and still be trans. You can regret taking steps that alienate you from your family, even as you wish your family would accept you living how you want to live. You can even regret some aspects of a treatment (any kind of medical treatment!) while being grateful for the knowledge you gained by trying it out. Regret doesn’t always mean that people wish they hadn’t transitioned, it just means that there are some parts of the story that they long to change.

Paul published a short follow-up in the Times pushing back on criticisms of her column, arguing that we simply don’t know how many trans teens will seek medical care and then go on to detransition. It’s true that we don’t have good U.S. data on the number of people who detransition, but other countries have fairly useful, recent papers showing that detransition is quite uncommon . Paul even cited one of these in her piece, although she dismissed it out of hand . It’s possible that we don’t have all the information yet, but we can consider the constellation of evidence that we do have. What’s clear from this evidence is that the vast majority of people do not experience regret, howsoever defined, after transitioning genders. Regret rates are actually much higher for a lot of medical procedures. For example, in the U.S. military study above, 26 percent of children stopped getting hormones through their parent’s insurance after four years; a national British study looking at antidepressant use in children across the country found that half of the kids had stopped taking these medications after just two months.

Ultimately, the question of what proportion of kids or adults regret their transition is only important to a select group: the people who want to transition, and their clinicians. At worst, the rate of regret is still better than other treatments which don’t require national debates over their use, which really begs the question of why anyone who isn’t directly involved with the treatment of transgender people is even weighing in on the topic at all. Indeed, a lot of what I’ve said in this piece has been raised by everyone from journalists to activists to trans folks just trying to live their lives. But as long as columnists are asking questions, maybe I can help by offering answers.

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Gender Dysphoria and Gender Reassignment Surgery

Decision summary.

Currently, the local Medicare Administrative Contractors (MACs) determine coverage of gender reassignment surgery on an individual claim basis. The Centers for Medicare & Medicaid Services (CMS) proposes to continue this practice and not issue a National Coverage Determination (NCD) at this time on gender reassignment surgery for Medicare beneficiaries with gender dysphoria.  Our review of the clinical evidence for gender reassignment surgery was inconclusive for the Medicare population at large.  The low number of clinical studies specifically about Medicare beneficiaries’ health outcomes for gender reassignment surgery and small sample sizes inhibited our ability to create clinical appropriateness criteria for cohorts of Medicare beneficiaries.

In the absence of a NCD, initial coverage determinations under section 1862(a)(1)(A) of the Social Security Act (the Act) and any other relevant statutory requirements will be made by the local Medicare Administrative Contractors (MACs) on an individual claim basis. 

While we are not issuing a NCD, CMS encourages robust clinical studies that will fill the evidence gaps and help inform the answer to the question posed in this proposed decision memorandum.  Based on the gaps identified in the clinical evidence, these studies should focus on which patients are most likely to achieve improved health outcomes with gender reassignment surgery, which types of surgery are most appropriate, and what types of physician criteria and care setting(s) are needed to ensure that patients achieve improved health outcomes.

We are requesting public comments on this proposed decision memorandum pursuant to section 1862(l)(3)(a) of the Act. We are specifically interested in public comments on the evidence we cited in this decision, comments containing any new evidence that has not been considered, and comments on whether a study could be developed that would support coverage with evidence development (CED), which would only cover gender reassignment surgery for beneficiaries who choose to participate in a clinical study.

Proposed Decision Memo

I. proposed decision.

Currently, the local Medicare Administrative Contractors (MACs) determine coverage of gender reassignment surgery on an individual claim basis. The Centers for Medicare & Medicaid Services (CMS) proposes to continue this practice and not issue a National Coverage Determination (NCD) at this time on gender reassignment surgery for Medicare beneficiaries with gender dysphoria. Our review of the clinical evidence for gender reassignment surgery was inconclusive for the Medicare population at large. The low number of clinical studies specifically about Medicare beneficiaries’ health outcomes for gender reassignment surgery and small sample sizes inhibited our ability to create clinical appropriateness criteria for cohorts of Medicare beneficiaries.

In the absence of a NCD, initial coverage determinations under section 1862(a)(1)(A) of the Social Security Act (the Act) and any other relevant statutory requirements will be made by the local Medicare Administrative Contractors (MACs) on an individual claim basis.

While we are not issuing a NCD, CMS encourages robust clinical studies that will fill the evidence gaps and help inform the answer to the question posed in this proposed decision memorandum. Based on the gaps identified in the clinical evidence, these studies should focus on which patients are most likely to achieve improved health outcomes with gender reassignment surgery, which types of surgery are most appropriate, and what types of physician criteria and care setting(s) are needed to ensure that patients achieve improved health outcomes.

II. Background

Below is a list of acronyms used throughout this document.

AHRQ - Agency for Healthcare Research and Quality AIDS - Acquired Immune Deficiency Syndrome ANOVA - Analysis of Variance APA - American Psychiatric Association APGAR - Adaptability, Partnership Growth, Affection, and Resolve test BIQ - Body Image Questionnaire BSRI - Bem Sex Role Inventory CCEI - Crown Crips Experimental Index CHIS - California Health Interview Survey CI - Confidence Interval CMS - Centers for Medicare & Medicaid Services DAB - Departmental Appeals Board DSM - Diagnostic and Statistical Manual of Mental Disorders EMBASE - Exerpta Medica dataBASE FBeK - Fragebogen zur Beurteilung des eigenen Korpers FDA - Food and Drug Administration FPI-R - Freiburg Personality Inventory FSFI - Female Sexual Function Index GAF - Global Assessment of Functioning GID - Gender Identity Disorder GIS - Gender Identity Trait Scale GRS - Gender Reassignment Surgery GSI - Global Severity Indices HADS - Hospital Anxiety Depression Scale HHS - U.S. Department of Health and Human Services HIV - Human Immunodeficiency Virus IIP - Inventory of Interpersonal Problems IOM - Institute of Medicine KHQ - King’s Health Questionnaire LGB - Lesbian, Gay, and Bisexual LGBT - Lesbian, Gay, Bisexual, and Transgender MAC - Medicare Administrative Contractor MMPI - Minnesota Multiphasic Personality Inventory NCA - National Coverage Analysis NCD - National Coverage Determination NICE - National Institute for Health Care Excellence NIH - National Institutes of Health NZHTA - New Zealand Health Technology Assessment PIT - Psychological Integration of Trans-sexuals QOL - Quality of Life S.D. - Standard Deviation SADS - Social Anxiety Depression Scale SCL-90R - Symptom Check List 90-Revised SDPE - Scale for Depersonalization Experiences SES - Self Esteem Scale SF - Short Form SMR - Standardized Mortality Ratio SOC – Standards of Care STAI-X1 - Spielberger State and Trait Anxiety Questionnaire STAI-X2 - Spielberger State and Trait Anxiety Questionnaire TSCS - Tennessee Self-Concept Scale U.S. - United States VAS - Visual Analog Scale WHOQOL-BREF - World Health Organization Quality of Life - Abbreviated version of the WHOQOL-100 WPATH - World Professional Association for Transgender Health

A.  Diagnostic Criteria

The criteria for gender dysphoria or spectrum of related conditions as defined by the American Psychiatric Association (APA) in the Diagnostic and Statistical Manual of Mental Disorders (DSM) has changed over time (See Appendix A).

Gender dysphoria (previously known as gender identity disorder) is a classification used to describe persons who experience significant discontent with their biological sex and/or gender assigned at birth. Therapeutic options for gender dysphoria include behavioral and psychotherapies, hormonal treatments, and a number of surgeries used for gender reassignment. This proposed decision is only focusing on gender reassignment surgery.

B.  Prevalence of Gender Dysphoria

Prevalence of gender dysphoria estimates have been reported by several investigators.

For estimates of transgender individuals in the U.S., we looked at several studies.

The Massachusetts Behavior Risk Factor Surveillance Survey (via telephone) (2007 and 2009) identified 0.5% individuals as transgender (Conron et al., 2012).

Derivative data obtained from the 2004 California Lesbian Gay Bisexual and Transgender (LGBT) Tobacco Survey (via telephone) and the 2009 California Health Interview Survey (CHIS) (via telephone) suggested the LGB population constitutes 3.2% of the California population and that transgender subjects constitute approximately 2% of the California LGBT population and 0.06% of the overall California population (Bye et al., 2005; CHIS 2009; Gates, 2011).

In a recent review of Medicare claims data, CMS estimated that in calendar year 2013 there were at least 4,098 transgender beneficiaries (less than 1% of the Medicare population) who utilized services paid for by Medicare, of which 90% had confirmatory diagnosis, billing codes, or evidence of a hormone therapy prescription. The Medicare transgender population is racially and ethnically diverse (e.g., 74% White, 15% African American) and spans the entire country. The following states have at least 100 transgender beneficiaries: California, Florida, Georgia, Illinois, Massachusetts, Michigan, Minnesota, New York, Pennsylvania, Ohio, Texas, Washington, and Wisconsin. Nearly 80% of transgender beneficiaries are under age 65, including approximately 23% ages 45-54. Of note, for the transgender population under age 65, the most prevalent chronic conditions were depression, major depressive affective disorder, and anxiety. Approximately 75% of transgender Medicare beneficiaries have been affected by depression, which is a disproportionately high amount compared to the Medicare population as a whole with 14% of Medicare fee-for-service beneficiaries suffering from the disease (CMS, Chronic Conditions Among Medicare Beneficiaries , 2012 at https://www.cms.gov/research-statistics-data-and-systems/statistics-trends-and-reports/chronic-conditions/downloads/2012chartbook.pdf). Based on the claims data, about 48% of transgender beneficiaries use hormone therapy, which are coverable under the Medicare Part D prescription drug benefit program (CMS Office of Minority Health (2015, June). New Directions in CMS Disparities Research: Sexual Orientation & Gender Identity. Paper presented at the Academy Health Annual Research Meeting, Minneapolis, Minnesota and Gay and Lesbian Medical Association Meeting, Portland, Oregon).

For international comparison purposes, recent estimates of transgender populations in other countries are similar to those in the United States. New Zealand researchers, using passport data, reported a prevalence of 0.0275% for male-to-female adults and 0.0044% female-to-male adults (6:1 ratio) (Veale, 2008). Researchers from a centers of transgender treatment and reassignment surgery in Belgium conducted a survey of regional plastic surgeons and reported a prevalence of 0.008% male-to-female and 0.003% female-to-male (ratio 2.7:1) surgically reassigned transsexuals in Belgium (De Cuypere et al., 2007). Swedish researchers, using national mandatory reporting data on those requesting reassignment surgery, reported secular changes over time in that the number of completed reassignment surgeries per application increased markedly in the 1990s; the male-to-female/female-to-male sex ratio changed from 1:1 to 2:1; the age of male-to-female and female-to-male applicants was initially similar, but increased by eight years for male-to-female applicants; and the proportion of foreign born applicants increased (Olsson, Moller 2003).

C.  Interventions

Table 1 provides information about some of the types of therapeutic interventions for transgender individuals.

Table 1. Types of Therapeutic Intervention (May Not be Exhaustive)

III. History of Medicare Coverage

CMS does not currently have an NCD on gender reassignment surgery.

A.  Current Request

On December 3, 2015, CMS accepted a formal complete request from a beneficiary to initiate a national coverage analysis (NCA) for gender reassignment surgery.

CMS opened this National Coverage Analysis (NCA) to thoroughly review the evidence to determine whether or not gender reassignment surgery may be covered nationally under the Medicare program.

B.  Benefit Category

Medicare is a defined benefit program. For an item or service to be covered by the Medicare program, it must fall within one of the statutorily defined benefit categories as outlined in the Act. For gender reassignment surgery, the following are statutes are applicable to coverage:

Under §1812 (Scope of Part A) Under §1832 (Scope of Part B) Under §1861(s) (Definition of Medical and Other Health Services) Under §1861(s)(1) (Physicians’ Services) This may not be an exhaustive list of all applicable Medicare benefit categories for this item or service.

IV. Timeline of Recent Activities

Table 2: Timeline of Medicare Coverage Policy Actions for Gender Reassignment Surgery

V. FDA Status

Surgical procedures per se are not subject to the Food and Drug Administration’s (FDA) approval.

Inflatable penile prosthetic devices, rigid penile implants, testicular prosthetic implants, and breast implants have been approved/cleared by the FDA.

VI. General Methodological Principles

In general, when making national coverage determinations, CMS evaluates relevant clinical evidence to determine whether or not the evidence is of sufficient quality to support a finding that an item or service is reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member. (§ 1862 (a)(1)(A)). The evidence may consist of external technology assessments, internal review of published and unpublished studies, recommendations from the Medicare Evidence Development & Coverage Advisory Committee (MEDCAC), evidence-based guidelines, professional society position statements, expert opinion, and public comments.

The overall objective for the critical appraisal of the evidence is to determine to what degree we are confident that: 1) specific clinical question relevant to the coverage request can be answered conclusively; and 2) the extent to which we are confident that the intervention will improve health outcomes for patients.

A detailed account of the methodological principles of study design the agency staff utilizes to assess the relevant literature on a therapeutic or diagnostic item or service for specific conditions can be found in Appendix B. In general, features of clinical studies that improve quality and decrease bias include the selection of a clinically relevant cohort, the consistent use of a single good reference standard, blinding of readers of the index test, and reference test results.

Public commenters sometimes cite the published clinical evidence and provide CMS with useful information. Public comments that provide information based on unpublished evidence, such as the results of individual practitioners or patients, are less rigorous and, therefore, less useful for making a coverage determination. CMS uses the initial comment period to inform the public of its proposed decision. CMS responds in detail to the public comments that were received in response to the proposed decision when it issues the final decision memorandum.

VII. Evidence

A.  Introduction

Below is a summary of the evidence we considered during our review, primarily articles about clinical trials published in peer-reviewed medical journals. We considered articles cited by the requestor, in public comments, as well as those found by a CMS literature review. Citations are detailed below.

B.  Literature Search Methods

CMS staff extensively searched for primary studies evaluating therapeutic interventions for gender dysphoria. There was particular emphasis on the various surgical interventions, but other treatments including hormone therapy, psychotherapy, psychiatric treatment, ancillary reproductive and gender modifying services, and post-operative surveillance services for natal sex organs were also included because of their serial and sometimes overlapping roles in patient management. The emphasis focused less on specific surgical techniques and more on functional outcomes unless specific techniques altered those types of outcomes.

The reviewed evidence included articles obtained by searching literature databases and technology review databases from PubMed (1965 to current date), EMBASE, the Agency for Healthcare Research and Quality (AHRQ), the Blue Cross/Blue Shield Technology Evaluation Center, the Cochrane Collection, the Institute of Medicine, and the National Institute for Health and Care Excellence (NICE) as well as the source material for commentary, guidelines, and formal evidence-based documents published by professional societies. Systematic reviews were used to help locate some of the more obscure publications and abstracts.

Keywords used in the search included: Trans-sexual, transgender, gender identity disorder (syndrome), gender dysphoria and/or hormone therapy, gender surgery, genital surgery, gender reassignment (surgery), sex reassignment (surgery) AND/OR quality of life, satisfaction-regret, psychological function (diagnosis of mood disorders, psychopathology, personality disorders), employment status, relationships, other social function, suicide (attempts), mortality, sexual function, urinary function, and adverse events-reoperations. After the identification of germane publications, CMS also conducted searches on the specific psychometric instruments used by investigators.

Psychometric instruments are scientific tools used to measure individuals' mental capabilities and behavioral style. They are usually in the form of questionnaires that numerically capture responses. These tools are used to create a psychological profile that can address questions about a person’s knowledge, abilities, attitudes and personality traits. In the evaluation of patients with gender dysphoria, it is important that both validity and reliability be assured in the construction of the tool (validity refers to how well the tool actually measures what it was designed to measure, or how well it reflects the reality it claims to represent, while reliability refers to how accurately results of the tool would be replicated in a second identical piece of research). That is because when evaluating patients with this condition most of the variables of interest (e.g., satisfaction, anxiety, depression) are latent in nature (not directly observed but are rather inferred) and difficult to quantify objectively.

Studies with robust study designs and larger, defined patient populations assessed with objective endpoints or validated test instruments were given greater weight than small, pilot studies. Reduced consideration was given to studies that were underpowered for the assessment of differences or changes known to be clinically important. Studies with fewer than 30 patients were reviewed and delineated, but excluded from the major analytic framework. Oral presentations, unpublished white papers, and case reports were excluded. Publications in languages other than English were excluded.

Included studies were limited to those with adult subjects. Review and discussion of the management of children and adolescents with the additional considerations of induced pubertal delay are outside the scope of this NCD. In cases where the same population was studied for multiple reasons or where the patient population was expanded over time, the latest and/or most germane sections of the publications were analyzed. The excluded duplicative publications are delineated.

CMS also searched Clinicaltrials.gov to identify relevant clinical trials. CMS looked at trial status including early termination, completed, and ongoing with sponsor update, and ongoing with estimated date of completion. Publications on completed trials were sought. The CMS internal search was limited to articles published prior to March 21, 2016. CMS reviewed results of clinical trials involving adult human subjects; to reports of prospective (e.g., blinded, non-blinded, cross sectional), partially prospective, retrospective longitudinal studies randomized meeting certain criteria.

C.  Discussion of Evidence

The development of an assessment in support of Medicare coverage determinations is based on the same general question for almost all national coverage analyses (NCAs): "Is the evidence sufficient to conclude that the application of the item or service under study will improve health outcomes for Medicare patients?" CMS is interested in answering the following question:

Is there sufficient evidence to conclude that gender reassignment surgery improves health outcomes for Medicare beneficiaries with gender dysphoria?

The evidence reviewed is directed towards answering this question.

1.  Internal Technology Assessment

When looking at the studies evaluating gender reassignment surgery for patients with gender dysphoria, we found an array of disparate research designs. Most of the studies were conducted in Europe. Only six studies took place in the U.S. (Ainsworth, Spiegel, 2010; Beatrice, 1985; Meyer, Reter, 1979; Newfield et al., 2006; Lawrence, 2006; Leinung et al., 2013). Most of the studies that evaluated gender dysphoria were descriptive in nature; few made inferences which may be applicable to the Medicare population.

CMS conducted an extensive literature search on gender reassignment related surgical procedures and on facets of gender dysphoria that provide context for this analysis. The latter includes medical and environmental conditions. CMS also explored the relative roles that psychological support, mental health care, cross-sex hormonal therapy, and the various gender reassignment related surgical procedures played in health outcomes.

CMS identified numerous publications related to gender reassignment surgery. A large number of these were case reports, case series with or without descriptive statistics, or studies with population sizes too small to conduct standard parametric statistical analyses. Others addressed issues of surgical technique.

CMS identified and described 36 publications on gender reassignment surgery that included health outcomes. Because the various investigators at a site sometimes conducted serial studies on ever-enlarging cohort populations, studied sub-populations, studied different outcomes, or used different tools to study the same outcomes, not all study populations were unique. To reduce bias from over-lapping populations, only the latest or most germane publication(s) were described. Subsumed publications were delineated.

Of these 36 publications, two publications used different assessment tools on the same population, and, so for the purposes of evaluation, were classified as 1 study (Udeze et al., 2008; Megeri, Khoosal, 2007). For another publication, the complete manuscript could not be located despite an exhaustive search by the Library of Medicine (Barrett, 1998). This precluded adequate review, thus, it was not included. A total of 33 studies were reviewed (See Figure 1). Appendices C, D, and F include more detail of each study.

The publications covered a time span from 1979 to 2015. Over half of the studies were published after 2005.

Figure 1. Studies of Gender Reassignment Surgery (GRS)

ANOVA=Analysis of Variance Normative=Psychometric Tests with known normative for large populations

The studies in Figure 1 are categorized into 3 groups. The first group, depicted by the colored boxes (red, blue, and green), had explicit controls. There was a single randomized study. The remainder in the first group were observational studies. These were subdivided into longitudinal studies and cross-sectional studies. The second group, depicted by black boxes (starting with the surgery only populations box) consisted of surgical series. The third group, depicted by black boxes (starting with mixed population), was composed of mixed populations of patients not stratified by treatment and which included a spectrum of therapeutic interventions.

When looking at the totality of studies, they fell into the following research design groups:

a. Prospective, non-blinded, observational, cross-sectional studies with no concurrent controls

Ainsworth TA, Spiegel JH. Quality of life of individuals with and without facial feminization surgery or gender reassignment surgery. Qual Life Res. 2010 Sep;19(7):1019-24.

Ainsworth and Spiegel conducted a prospective, observational study using a cross-sectional design and a partially self-designed survey tool. The blind status is unknown. Treatment types served as the basis for controls.

The investigators, head and neck surgeons who provided facial feminization services, assessed perception of appearance and quality of life in male-to-female subjects with self-reported gender dysphoria. Patients could have received no therapeutic intervention, hormone therapy, reassignment surgery, and/or facial feminization surgery and an unrestricted length of transition. (Transition refers to the time when a transgender person begins to live as the gender with which they identify rather than the gender assigned at birth.) Criteria for the various types of interventions were not available because of the survey design of the study. Patients were recruited via website or at a 2007 health conference. Pre-specified controls to eliminate duplicate responders were not provided. The investigators employed a self-designed Likert-style facial feminization outcomes evaluation questionnaire and a “San Francisco 36” health questionnaire. No citations were provided for the latter. It appears to be the Short-form (SF) 36-version 2. Changes or differences considered to be biologically significant were not pre-specified. Power corrections for multiple comparisons were not provided.

The investigators reported that there were 247 participants. (The numbers of incomplete questionnaires was not reported.) Of the 247 participants, 25 (10.1%) received only primary sex trait reassignment surgery, 28 (11.3%) received facial surgery without primary sex trait reassignment surgery, 47 (19.0%) received both facial and primary sex trait reassignment surgery, and 147 (59.5%) received neither facial nor reassignment surgery. The mean age for each of these cohorts was: 50 (no standard deviation [S.D.]) only reassignment surgery, 51 (no S.D.) only facial surgery, 49 (no S.D.) both types of surgery, and 46 (no S.D.) (neither surgery). Of the surgical cohorts: 100% of those who had undergone primary sex trait reassignment surgery alone used hormone therapy, 86% of those who had undergone facial feminization used hormone therapy, and 98% of those who had undergone both primary sex trait reassignment surgery and facial feminization used hormone therapy. In contrast to the surgical cohorts, 66% of the “no surgery” cohort used hormonal therapy, and a large proportion (27%) had been in transition for less than 1 year.

The investigators reported higher scores on the facial outcomes evaluation in those who had undergone facial feminization. Scores of the surgical cohorts for the presumptive SF-36 comprehensive mental health domain did not differ from the general U.S. female population. Scores of the “no surgery” cohort for the comprehensive mental health domain were statistically lower than those of the general U.S. female population, but within 1 standard deviation of the normative mean. Mean scores of all the gender dysphoric cohorts for the comprehensive physical domain were statistically higher than those of the general female U.S. population, but were well within 1 standard deviation of the normative mean. Analyses of inter-cohort differences for the SF-36 results were not conducted. Although the investigators commented on the potential disproportionate impact of hormone therapy on outcomes and differences in the time in “transition”, they did not conduct any statistical analyses to correct for putative confounding variables.

Motmans J , Meier P, Ponnet K, T'Sjoen G. Female and male transgender quality of life: socioeconomic and medical differences. J Sex Med. 2012 Mar;9(3):743-50. Epub 2011 Dec 21.

Motmans et al., conducted a prospective, non-blinded, observational study using a cross-sectional design and a non-specific quality-of-life tool. No concurrent controls were used in this study. Quality of life in this Dutch-speaking population was assessed using the Dutch version of a SF-36 (normative data was used). Participants included subjects who were living in accordance with the preferred gender and who were from a single, unspecified, Belgian university specialty clinic. The Dutch version of the SF-36 questionnaire along with its normative data were used. Variables explored included employment, pension status, ability to work, being involved in a relationship. Also explored, was surgical reassignment surgery and the types of surgical interventions. Intragroup comparisons by transgender category were conducted, and the relationships between variables were assessed by analysis of variance (ANOVA) and correlations.

The age of the entire cohort (n=140) was 39.89±10.21 (female-to-male: 37.03±8.51; male-to-female: 42.26±10.39). Results of the analysis revealed that not all female-to-male patients underwent surgical reassignment surgery and, of those who did, not all underwent complete surgical reassignment. The numbers of female-to-male surgical interventions were: mastectomy 55, hysterectomy 55, metadoiplasty 8 (with 5 of these later having phalloplasty), phalloplasty 40, and implantation of a prosthetic erectile device 20. The frequencies of various male-to-female surgical interventions were: vaginoplasty 48, breast augmentation 39, thyroid cartilage reduction 17, facial feminization 14, and hair transplantation 3.

The final number of subjects with SF-36 scores was 103 (49 [47.6%] female-to-male; 54 [52.4%] male-to-female; ratio 1:1.1). For this measure, the scores for the vitality and mental health domains for the final female-to-male cohort (n= 49 and not limited to those having undergone some element of reassignment surgery) were statistically lower: 60.61±18.16 versus 71.9±18.31 and 71.51±16.40 versus 79.3±16.4 respectively. Scores were not different from the normative data for Dutch women: vitality: 64.3±19.7 or mental health 73.7±18.2. None of the domains of the SF-36 for the final male-to-female cohort (n=54 and not limited to those having undergone some element of reassignment surgery) were statistically different from the normative data for Dutch women.

Analysis of variance indicated that quality-of-life as measured by the SF-36 did not differ by whether female-to-male patients had undergone genital surgery (metadoidoplasty or phalloplasty) or not. Also, ANOVA indicated that quality-of-life as measured by the SF-36 did not differ by whether male-to-female patients had undergone either breast augmentation or genital surgery (vaginoplasty) or not.

Whether there is overlap with the Ghent populations studied by Heylens et al., Weyers et al., or Wierckx et al. is unknown.

Weyers S, Elaut E, De Sutter P, Gerris J, T'Sjoen G, Heylens G, De Cuypere G, Verstraelen H. Long-term assessment of the physical, mental, and sexual health among transsexual women. J Sex Med. 2009 Mar;6(3):752-60. Epub 2008 Nov 17.

Weyers at al. 2009 conducted a prospective, non-blinded, observational study using a cross-sectional design and several measurement instruments including a non-specific quality of life tool and a semi-specific quality of life tool (using normative data) along with 2 self-designed tools.

The investigators assessed general quality of life, sexual function, and body image from the prior 4 weeks in Dutch-speaking male-to-female patients with gender dysphoria who attended a single-center, specialized, comprehensive care university clinic. Investigators used the Dutch version of the SF-36 and results were compared to normative data from Dutch women and U.S. women. The 19 items of the Dutch version of the Female Sexual Function Index (FSFI) were used to measure sexual desire, function, and satisfaction. A self-designed 7 question visual analog scale (VAS) was used to measure satisfaction with gender related body traits and appearance perception by self and others. A self-designed survey measured a broad variety of questions regarding personal medical history, familial medical history, relationships, importance of sex, sexual orientation, gynecologic care, level of regret, and other health concerns. For this study, hormone levels were also obtained.

The study consisted of 50 participants. Analysis of the data revealed that the patient’s average age was 43.1 ±10.4 years, and all of the patients had vaginoplasty. This same population also had undergone additional feminization surgical procedures (breast augmentation 96.0%, facial feminization 36.0%, vocal cord surgery 40.0%, and cricoid cartilage reduction 30.0%). A total of two (4.0%) participants reported “sometimes” regretting reassignment surgery and 23 (46.0%) were not in a relationship. For the cohort, estradiol, testosterone, and sex hormone binding globulin levels were in the expected range for the reassigned gender. The SF-36 survey revealed that the subscale scores of the participants did not differ substantively from those of Dutch and U.S. women. VAS scores of body image were highest for self-image, appearance to others, breasts, and vulva/vagina (approximately 7 to 8 of 10). Scores were lowest for body hair, facial hair, and voice characteristics (approximately 6 to 7 of 10).

The total FSFI score was 16.95±10.04 out of a maximal 36. The FSFI scores averaged 2.8 (6 point maximum): satisfaction 3.46±1.57, desire 3.12+1.47, arousal 2.95±2.17, lubrication 2.39±2.29, orgasm 2.82±2.29, and pain 2.21±2.46. Though these numbers were reported in the study, data on test population controls were not provided. VAS scores of body image were highest for self-image, appearance to others, breasts, and vulva/vagina (approximately 7 to 8 of 10). Scores were lowest for body hair, facial hair, and voice characteristics (approximately 6 to 7 of 10).

A post hoc exploration of the data was performed that revealed the following: perceived improvement in general health status was greater in the subset that had undergone reassignment surgery within the last year; sexual orientation impacted the likelihood of being in a relationship; SF-36 scores for vitality, social functioning, and mental health were nominally better for those in relationships, but that overall SF-36 scores did not differ by relationship status; sexual orientation and being in a relationship impacted FSFI scores; and reported sexual function was higher in those with higher satisfaction with regards to their appearance.

Wierckx K, Van Caenegem E, Elaut E, Dedecker D, Van de Peer F, Toye K, Weyers S, Hoebeke P, Monstrey S, De Cuypere G, T'Sjoen G. Quality of life and sexual health after sex reassignment surgery in transsexual men. J Sex Med. 2011 Dec;8(12):3379-88. Epub 2011 Jun 23.

Wierckx at al. conducted a prospective, non-blinded, observational study using a cross-sectional design and several measurement instruments (a non-specific quality of life tool with reported normative data along with 3 self-designed tools). The investigators assessed general quality of life, sexual relationships, and surgical complications in Dutch-speaking female-to-male patients with gender dysphoria who attended a single-center, specialized, comprehensive care, university clinic. Investigators used the Dutch version of the SF-36 with 36 questions, 8 subscales, and 2 domains evaluating physical and mental health. Results were compared to normative data from Dutch women and Dutch men. Self -designed questionnaires to evaluate aspects of medical history, sexual functioning (there were separate versions for those with and without partners), and surgical results were also used. The Likert-style format was used for many of the questions.

A total of 79 female-to-male patients with gender dysphoria had undergone reassignment surgery were contacted; however, ultimately, 47 (59.5%) chose to participate. Three additional patients were recruited by other patients. One of the 50 participants was later excluded for undergoing reassignment surgery within the 1 year window. The age of patients was: 30±8.2 years (range 16 to 49) at the time of reassignment surgery and 37.1 ±8.2 years (range 22 to 54) at the time of follow-up. The time since hysterectomy, oopherectomy, and mastectomy was 8 years (range 2 to 22). The patient population had undergone additional surgical procedures: metaidoiplasty (n=9; 18.4%), phalloplasty (n=8 after metaidoiplasty, 38 directly; 93.9% total), and implantation of erectile prosthetic device (n=32; 65.3%). All had started hormonal therapy at least 2 years prior to surgery and continued to use androgens.

The SF-36 survey was completed by 47 (95.9%) participants. The “Vitality” and the “Mental Health” scales were lower than the Dutch male population: 62.1±20.7 versus 71.9±18.3 and 72.6±19.2 versus 79.3±16.4 respectively. These subscale scores were equivalent to the mean scores of the Dutch women.

None of the participants were dissatisfied with their hysterectomy-oopherectomy procedures; 4.1% were dissatisfied with their mastectomies because of extensive scarring; and 2.2% were dissatisfied with their phalloplasties. Of the participants, 17.9% were dissatisfied with the implantation of an erectile prosthetic device; 25 (51.0%) reported at least one post-operative complication associated with phalloplasty (e.g., infection, urethrostenosis, or fistula formation); 16 (50.0% of the 32 with an erectile prosthetic device) reported at least one post-operative complication associated with implantation of an erectile prosthetic (e.g., infection, leakage, incorrect positioning, or lack of function).

A total of 18 (36.7%) participants were not in a relationship; 12.2% reported the inability to achieve orgasm with self-stimulation less than half the time; 12.2% did not respond to the question. Of those with participants with partners, 28.5% reported the inability to achieve orgasm with intercourse less than half the time and 9.7% did not respond to this question. Also, 61.3% of those with partners reported (a) no sexual activities (19.4%) or (b) activities once or twice monthly (41.9%), and there were 12.9% who declined to answer.

Post hoc assessments suggested that being in relationship or having undergone phalloplasty did not impact the scores of the SF-36 domains. Also this assessment suggested that for patients in a relationship, sexual satisfaction was related to “Vitality” scores. Finally this assessment suggested a relationship between sexual satisfaction and more frequent orgasm and pleasure with the partner.

Salvador J, Massuda R, Andreazza T, Koff WJ, Silveira E, Kreische F, de Souza L, de Oliveira MH, Rosito T, Fernandes BS, Lobato MI. Minimum 2-year follow up of sex reassignment surgery in Brazilian male-to-female transsexuals. Psychiatry Clin Neurosci. 2012 Jun;66(4):371-2. PMID: 22624747.

Salvador et al. conducted a prospective, non-blinded, observational study using a cross-sectional design (albeit over an extended time interval) and a self-designed quality of life tool. The investigators assessed regret, sexual function, partnerships, and family relationships in patients who had undergone gender reassignment surgery at least 24 months prior.

Out of the 243 enrolled in the clinic over a 10 year interval, 52 patients agreed to participate in the study. The age at follow-up was 36.3±8.9 (range 15-58) years with the time to follow-up being 3.8±1.7 (2-7) years. A total of 46 participants reported pleasurable neo-vaginal sex and post-surgical improvement in the quality of their sexual experience. The quality of sexual intercourse was rated as satisfactory to excellent, average, unsatisfactory, or not applicable in the absence of sexual contact by 84.6%, 9.6%, 1.9%, and 3.8% respectively. Of the participants, 78.8% reported greater ease in initiating and maintaining relationships; 65.4% reported having a partner; 67.3% reported increased frequency of intercourse; 36.8% reported improved familial relationships. No patient reported regret over reassignment surgery. The authors did not provide information about incomplete questionnaires.

Blanchard R, Steiner BW, Clemmensen LH. Gender dysphoria, gender reorientation, and the clinical management of transsexualism. J Consult Clin Psychol. 1985 Jun;53(3):295-304.

Blanchard et al. conducted a prospective, non-blinded, cross-sectional study using a self-designed questionnaire and a non-specific psychological symptom assessment with normative data. The investigators assessed social adjustment and psychopathology in patients with gender dysphoria and who were at least 1 year post gender reassignment surgery. Reassignment surgery was defined as either vaginoplasty or mastectomy/construction of male chest contour with or without nipple transplants, but did not preclude additional procedures. Partner preference was determined using the Modified Androphilia-Gynephilia Index, and the nature and extent of any psychopathology was determined with the Symptom Check List 90-Revised (SCL-90R).

Of the 294 patients (111 natal females and 183 natal males, ratio: 1:1.65) initially evaluated, 79 patients participated in the study (38 female-to-male; 32 male-to-female with male partner preference; 9 male-to-female with female partner preference). The respective mean ages for these 3 groups were 32.6, 33.2, and 47.7 years with the last group being older statistically (p=0.01). Additional surgeries in female-to-male patients included: oophorectomy/hysterectomy 92.1% and phalloplasty 7.9%. Additional procedures in male-to-female patients with male partner preference included facial hair electrolysis 62.5% and breast implantation 53.1%. Additional procedures in male-to-female patients with female partner preference included facial hair electrolysis 100% and breast implantation 33.3%. The time between reassignment surgery and questionnaire completion did not differ by group.

Psychopathology as measured by the Global Severity Index of the SCL-90R was absent in all 3 patient groups. Interpretation did not differ by the sex of the normative cohort.

Of participants, 63.2% of female-to-male patients cohabitated with partners of their natal gender. 46.9% of male-to-female patients with male partner preference cohabitated with partners of their natal gender; 93.7% reported that they would definitely undergo reassignment surgery again. The remaining 6.3% (1 female-to-male; 1 male-to-female with male partner preference; 3 male-to-female with female partner preference) indicated that they probably would undertake the surgery again. Post hoc analysis suggested that the more ambivalent responders had more recently undergone surgery. Of responders, 98.7% indicated that they preferred life in the reassigned gender. The one ambivalent subject was a skilled and well compensated tradesperson who was unable to return to work in her male dominated occupation.

Tsoi WF. Follow-up study of transsexuals after sex-reassignment surgery. Singapore Med J. 1993 Dec;34(6):515-7.

Tsoi conducted a prospective, non-blinded, observational study using a cross-sectional design and a self-designed quality of life tool. The investigators assessed overall life satisfaction, employment, partner status, and sexual function in gender-reassigned persons who had undergone gender reassignment surgery between 1972 and 1988 inclusive and who were approximately 2 to 5 years post-surgery. Acceptance criteria for surgery included good physical health, good mental health, absence of heterosexual tendencies, willingness to undergo hormonal therapy for ≥6 months, and willingness to function in the life of the desired gender for ≥6 months. Tsoi also undertook retrospective identification of variables that could predict outcomes.

The size of the pool of available patients was not identified. Of the 81 participants, 36 were female-to-male (44.4%) and 45 were male-to-female (55.6%) (ratio 1:1.25).

The mean ages at the time of the initial visit and operation were: female-to-male 25.4±4.4 (range 14-36) and 27.4 ±4.0; (range 14-36); male-to-female 22.9±4.6 (range 14-36) and 24.7±4.3 (14-36) years respectively. Of all participants, 14.8% were under age 20 at the time of the initial visit. All were at least 20 at the time of gender reassignment surgery. The reported age of onset was 8.6 years for female-to-male patients and 8.7 years for male-to-female patients.

All participants reported dressing without difficulty in the reassigned gender; 95% of patients reported good or satisfactory adjustment in employment and income status; 72% reported good or satisfactory adjustment in relationships with partners. Although the quality of life tool was self-designed, 81% reported good or satisfactory adjustment to their new gender, and 63% reported good or acceptable satisfaction with sexual activity. Of the female-to-male patients, 39% reported good or acceptable satisfaction with sex organ function in comparison to 91% of male-to-female patients (p<0.001). (The author reported that a fully functioning neo-phallus could not be constructed at the time.) The age of non-intercourse sexual activity was the only predictor of an improved outcome.

Gómez-Gil E, Zubiaurre-Elorza L, Esteva I, Guillamon A, Godás T, Cruz Almaraz M, Halperin I, Salamero M. Hormone-treated transsexuals report less social distress, anxiety and depression. Psychoneuroendocrinology. 2012 May;37(5):662-70. Epub 2011 Sep 19.

Gómez-Gil et al. conducted a prospective, non-blinded observational study using a cross-sectional design and non-specific psychiatric distress tools in Spain. The investigators assessed anxiety and depression in patients with gender dysphoria who attended a single-center specialty clinic with comprehensive endocrine, psychological, psychiatric, and surgical care. The clinic employed World Professional Association for Transgender Health (WPATH) guidelines. Patients were required to have met diagnostic criteria during evaluations by 2 experts. Investigators used the Hospital Anxiety and Depression Scale (HADS) and the Social Anxiety and Distress Scale (SADS) instruments. The SADS total score ranges from 0 to 28, with higher scores indicative of more anxiety. English language normative values are 9.1±8.0. HAD-anxiety and HAD-depression total score ranges from 0 to 21, with higher scores indicative of more pathology. Scores less than 8 are normal. ANOVA was used to explore effects of hormone and surgical treatment.

Of the 200 consecutively selected patients recruited, 187 (93.5% of recruited) were included in the final study population. Of the final study population, 74 (39.6%) were female-to-male patients; 113 (60.4%) were male-to-female patients (ratio 1:1.5); and 120 (64.2%) were using hormones. Of those using hormones, 36 (30.0%) were female-to-male; 84 (70.0%) were male-to-female (ratio 1:2.3). The mean age was 29.87±9.15 (range 15-61). The current age of patients using hormones was 33.6±9.1 (n=120) and older than the age of patients without hormone treatment (25.9±7.5) (p=0.001). The age at hormone initiation, however, was 24.6±8.1.

Of those who had undergone reassignment surgery, 29 (36.7%) were female-to-male; 50 (63.3%) were male-to-female; ratio 1:1.7. The number of patients not on hormones and who had undergone at least 1 gender-related surgical procedure (genital or non-genital) was small (n=2). The number of female-to-male patients on hormones who had undergone such surgery (mastectomy, hysterectomy, or phalloplasty) was 28 (77.8%). The number of male-to-female patients on hormones who had undergone such surgery (mammoplasty, facial feminization, buttock feminization, vaginoplasty, orchiectomy, and vocal feminization (thyroid chondroplasty) was 49 (58.3%).

Analysis of the data revealed that although the mean scores HAD-Anxiety, HAD-Depression, and SADS were statistically lower (better) in those on hormone therapy than in those not on hormone therapy, the mean scores for HAD-Depression and SADS were in the normal range for gender dysphoric patients not using hormones. The HAD-Anxiety score was borderline elevated and consistent with a possible mood disorder in patients not using hormones. The mean scores for HAD-Anxiety, HAD-Depression, and SADS were in the normal range for gender dysphoric patients using hormones. ANOVA revealed that results did not differ by whether the patient had undergone a gender related surgical procedure or not.

Gómez-Gil E, Zubiaurre-Elorza L, de Antonio I, Guillamon A, Salamero M. Determinants of quality of life in Spanish transsexuals attending a gender unit before genital sex reassignment surgery. Qual Life Res. 2014 Mar;23(2):669-76. Epub 2013 Aug 13.

Gómez-Gil et al. conducted a prospective, non-blinded observational study using a non-specific quality of life tool. There were no formal controls for this mixed population ± non-genital reassignment surgery. The investigators assessed quality of life in the context of culture in patients with gender dysphoria who were from a single-center, specialty and gender identity clinic. The clinic used WPATH guidelines. Patients were required to have met diagnostic criteria during evaluations by both a psychologist and psychiatrist. Patients could have undergone non-genital surgeries, but NOT genital reassignment surgeries (e.g., orchiectomy, vaginoplasty, or phalloplasty).

The Spanish version of the World Health Organization Quality of Life-Abbreviated version of the WHOQOL-100 (WHOQOL-BREF) was used to evaluate quality-of-life, which has 4 domains (environmental, physical, psychological, and social) and 2 general questions. Family dynamics were assessed with the Spanish version of the Family Adaptability, Partnership Growth, Affection, and Resolve (APGAR) test. Regression analysis was used to explore effects of surgical treatment.

Of the 277 patients recruited, 260 (93.9%) agreed to participate. Of this number, 193 were included in the study (the mean age of this group was 31.2±9.9 (range 16-67). Of these, 74 (38.3%) were female-to-male patients; 119 (61.7%) were male-to- female patients; ratio1:1.6. 120 (62.2%) were on hormone therapy; 29 (39.2%) of female-to-male patients had undergone at least 1 non-genital, surgical procedure (hysterectomy n=19 (25.7%); mastectomy n=29 (39.2%)); 51 (42.9%) of male-to-female patients had undergone at least 1 non-genital surgical procedure with mammoplasty augmentation being the most common procedure, n=47 (39.5%), followed by facial feminization, n=11 (9.2%), buttocks feminization, n=9 (7.6%), and vocal feminization (thyroid chondroplasty), n=2 (1.7%).

WHOQOL-BREF domain scores for gender dysphoric patients with and without non-genital surgery were: “Environmental” 58.81±14.89 (range 12.50-96.88), “Physical” 63.51±17.79 (range 14.29-100), “Psychological” 56.09+16.27 (range 16.67-56.09), “Social” 60.35±21.88 (range 8.33-100), and “Global QOL and Health” 55.44+27.18 (range 0-100). The mean APGAR family score was 7.23±2.86 (range 0-10).

Regression analysis, which was used to assess the relative importance of various factors to WHOQOL-BREF domains and general questions, revealed that family support was an important element for all 4 domains and the general health and quality-of-life questions. Hormone therapy was an important element for the general questions and for all of the domains except “Environmental.” Having undergone non-genital reassignment surgery, like age, educational levels, and partnership status, did not impact domain and general question results related to quality of life.

Mate-Kole C, Freschi M, Robin A. Aspects of psychiatric symptoms at different stages in the treatment of transsexualism. Br J Psychiatry. 1988 Apr;152:550-3.

Mate-Kole at al. conducted a prospective non-blinded, observational study using a cross-sectional design and 2 psychological tests (1 with some normative data). Concurrent controls were used in this study design. The investigators assessed neuroticism and sex role in natal males with gender dysphoria. Patients at various stages of management, (i.e., under evaluation, using cross-sex hormones, or post reassignment surgery [6 months to 2 years]) were matched by age of cross-dressing onset, childhood neuroticism, personal psychiatric history, and family psychiatric history. Both a psychologist and psychiatrist conducted assessments. The instruments used were the Crown Crisp Experiential Index (CCEI) for psychoneurotic symptoms and the Bem Sex Role Inventory. ANOVA was used to identify differences between the three treatment cohorts.

For each cohort, investigators recruited 50 male-to-female patients. The mean ages of the three cohorts were as follows: undergoing evaluation: mean age 34 years; wait-listed: mean age 35 years; and post-operative: mean age 37 years. Of the groups under evaluation or postsurgical, 16% (8 each) were unemployed; 8% of the waited listed patients were unemployed. For the cohorts, 22% of those under evaluation, 24% of those on hormone treatment only, and 30% of those post-surgery had prior psychiatric histories, and 24%, 24%, and 14% of the same respective cohorts had a history of attempted suicide. More than 30% of patients in each cohort had a first degree relative with a history of psychiatric disease.

The scores for the individual CCEI domains for depression and somatic anxiety were relatively higher (worse) for patients under evaluation than those on hormone treatment alone. The scores for all of the individual CCEI domains (free floating anxiety, phobic anxiety, somatic anxiety, depression, hysteria, and obsessionality) were lower in the post-operative cohort than in the other 2 cohorts.

The Bem Sex Role Inventory masculinity score for the combined cohorts was lower than for North American norms for either men or women. The femininity score for the combined cohorts was higher than for North American norms for either men or women. Those who were undergoing evaluation had the most divergent scores from North American norms and from the other treatment cohorts. Absolute differences were small. All scores of gender dysphoric patients averaged between 3.95 and 5.33 on a 7 point scale while the normative scores averaged between 4.59 and 5.12.

Eldh J, Berg A, Gustafsson M. Long-term follow up after sex reassignment surgery. Scand J Plast Reconstr Surg Hand Surg. 1997 Mar;31(1):39-45.

Eldh et al. conducted a non-blinded, observational study using a prospective cross-sectional design with a self-designed questionnaire and retrospective acquisition of pre-operative data. The investigators assessed economic circumstances, family status, satisfaction with surgical results, and sexual function in patients who had undergone gender reassignment surgery. Of the 175 patients who underwent reassignment surgery in Sweden, 90 responded. Of this number, 50 were female-to-male and 40 were male-to-female (ratio: 1:0.8). Patients reportedly were generally satisfied with the appearance of the reconstructed genitalia (no numbers provided). Of the patients who had undergone surgery prior to 1986, seven (14%) were dissatisfied with shape or size of the neo-phallus; 8 (16%) declined comment. There were 14 (35%), with 12 having surgery prior to 1986 and two between 1986 and 1995 inclusive, were moderately satisfied because of insufficient vaginal volume; 8 (20%) declined comment. A neo-clitoris was not constructed until the later surgical cohort. Three of 33 reported no sensation or no sexual sensation. Eight had difficulties comprehending the question and did not respond.

A total of nine (18%) patients had doubts about their gender orientation; 13 (26%) declined to answer the question; 44 (27 [61.3%] female-to-male and 17 [38.6%] male-to-female) were unmarried or without a steady partner; 19 (38.0%) female-to-male patients reported the absence of a sex life (28.0% declined to answer this particular question); 15 (30%) male-to-female reported dissatisfaction with their sex lives. Additionally, 3 (6.0%) reported absence of sexual activity post-operatively. Ten (11.1%) were dissatisfied with their life situation (17.8% declined to answer this question). The study found that 2 female-to-male patients and 2 male-to-female patients regretted their reassignment surgery and continued to live as the natal gender, and two patients attempted suicide.

Hepp U, Kraemer B, Schnyder U, Miller N, Delsignore A. Psychiatric comorbidity in gender identity disorder. J Psychosom Res. 2005 Mar;58(3):259-61.

Hepp et al. conducted a prospective, non-blinded, observational study using a cross-sectional design. There was some acquisition of retrospective data. The investigators assessed current and lifetime psychiatry co-morbidity using structured interviews for diagnosis of Axis 1 disorders (clinical syndromes) and Axis 2 disorders (developmental or personality disorders) and HADS for dimensional evaluation of anxiety and depression. Statistical description of the cohort and intra-group comparisons was performed. Continuous variables were compared using t-tests and ANOVA.

A total of 31 patients with gender dysphoria participated in the study: 11 (35.5%) female-to-male; 20 (64.5%) male-to-female (ratio 1:1.8). The overall mean age was 32.2±10.3. Of the participants, seven had undergone reassignment surgery, 10 pre-surgical patients had been prescribed hormone therapy, and 14 pre-surgical patients had not been prescribed hormone therapy. Forty five and one half percent of female-to-male and 20% of male-to-female patients did not carry a lifetime diagnosis of an Axis 1 condition. Sixty three and six tenths percent of female-to-male and 60% of male-to-female patients did not carry a current diagnosis of an Axis 1 condition. Lifetime diagnosis of substance abuse and mood disorder were more common in male-to-female patients (50% and 55% respectively) than female-to-male patients (36.4% and 27.3% respectively). Current diagnosis of substance abuse and mood disorder were present in male-to-female patients (15% and 20% respectively) and absent in female-to-male patients. One or more personality disorders were identified 41.9%, but whether this was a current or lifetime condition was not specified. Of the patients, five (16.1%) had a Cluster A personality disorder (paranoid-schizoid), seven (22.6%) had a Cluster B personality disorder (borderline, anti-social, histrionic, narcissistic), six (19.4%) had a Cluster C personality disorder (avoidant, dependent, obsessive-compulsive), and two (6.5%) were not otherwise classified.

The HADS test revealed non-pathologic results for depression (female-to-male: 6.64±5.03; male-to-female: 6.58±4.21) and borderline results for anxiety (female-to-male: 7.09±5.11; male-to-female: 7.74±6.13, where a result of 7-10 = possible disorder). There were no differences by natal gender. HADS scores were missing for at least 1 person. The investigators reported a trend for less anxiety and depression as measured by HADS in the patients who had undergone surgery.

b. Prospective, non-blinded, observational, cross-sectional studies with patients serving as their own controls

Rakic Z, Starcevic V, Maric J, Kelin K. The outcome of sex reassignment surgery in Belgrade: 32 patients of both sexes. Arch Sex Behav. 1996 Oct;25(5):515-25.

Rakic et al. conducted a prospective, non-blinded, observational study using a cross-sectional design and an investigator-designed quality of life tool that asked longitudinal (pre- and post-treatment) questions. Patients served as their own controls. The authors state that the study was not designed to assess the predictors of poor outcomes.

The investigators assessed global satisfaction, body image, relationships, employment status, and sexual function in patients with gender dysphoria who underwent reassignment surgery between 1989 and 1993 and were at least 6 months post-operative. The criteria to qualify for gender surgery were delineated (1985 standards from the Harry Benjamin International Gender Dysphoria Association) and included cross-gender behavior for at least 1 year. The questionnaire consisted of 10 questions using yes/no answers or Likert-type scales. Findings were descriptive without statistical analysis. As such, changes or differences considered to be biologically significant were not pre-specified, and there were no adjustments for multiple comparisons.

Of the 38 patients who had undergone reassignment surgery, 32 participated in the study 10 (31.2%) female-to-male and 22 (68.8%) male-to-female (ratio 1:2.2). The duration of follow-up was 21.8 ±13.4 months (range 6 months to 4 years). The age was female-to-male 27.8±5.2 (range 23-37) and male-to-female 26.4±7.8 (range 19-47).

Using an investigator-designed quality of life tool, all patients reported satisfaction with having undergone the surgery. Of the total participants, four (12.5%) (all male-to-female) and 8 (25%) (87.5% male-to-female) reported complete dissatisfaction or partial satisfaction with their appearance. Regarding relationships, 80% of female-to-male and 100% of male-to-female patients were dissatisfied with their relationships with others prior to surgery; whereas, no female-to-male patients and 18.1% of male-to-female patients were dissatisfied with relationships after surgery. Regarding sexual partners, 60% of female-to-male and 72.7% of male-to-female patients reported not having a sexual partner prior to surgery; whereas, 20% of female-to-male patients and 27.3% of male-to-female patients did not have a sexual partner after surgery. Of those with partners at each time interval, 100% of female-to-male and 50% of male-to-female patients reported not experiencing orgasm prior to surgery; whereas, 75% of female-to-male and 37.5% of male-to-female patients reported not experiencing orgasm after surgery. Fifty percent of female-to-male and 54.5% of male-to-female patients reported being either unemployed or not being a student full-time prior to surgery. After surgery, no female-to-male patients and 7 (31.8%) male-to-female patients reported being either unemployed or not being a student full-time. The change was due to student status. Six (60%) of female-to-male patients and 15 (68.2%) of male-to-female patients reported being unemployed before and after surgery.

c. Prospective, non-blinded, observational, cross-sectional studies with controls

Wolfradt U, Neumann K. Depersonalization, self-esteem and body image in male-to-female transsexuals compared to male and female controls. Arch Sex Behav. 2001 Jun;30(3):301-10.

Wolfradt and Neumann conducted a controlled, prospective, non-blinded, observational study using a cross-sectional design. The investigators assessed aspects of personality in male-to-female patients who had undergone vocal cord surgery for voice feminization and in healthy volunteers from the region. The patients had undergone gender reassignment surgery 1 to 5 years prior to voice surgery. The volunteers were matched by age and occupation. The primary hypothesis was that depersonalization, with the sense of being detached from one’s body or mental processes, would be more common in male-to-female patients with gender dysphoria. German versions of the Scale for Depersonalization Experiences (SDPE), the Body Image Questionnaire (BIQ), a Gender Identity Trait Scale (GIS), and the Self-Esteem Scale (SES) were used in addition to a question regarding global satisfaction. Three of the assessments used a 5 point scale (BIQ, GIS, and SDPE) for questions. One used a 4 point scale (SES). Another used a 7 point scale (global satisfaction). The study consisted of 30 male-to-female patients, 30 healthy female volunteers, and 30 healthy male volunteers. The mean age of study participants was 43 (range 29-67).

Results of the study revealed that there were no differences between the three groups for the mean scores of measures assessing depersonalization, global satisfaction, the integration of masculine traits, and body-image-rejected (subset). Also, the sense of femininity was equivalent for male-to-female patients and female controls and higher than that in male controls. The levels of self-esteem and body image-dynamic (subset) were equivalent for male-to-female patients and male controls and higher than that in female controls, and none of the numeric differences between means exceeded 0.61 units.

Beatrice J. A psychological comparison of heterosexuals, transvestites, preoperative transsexuals, and postoperative transsexuals. J Nerv Ment Dis. 1985 Jun;173(6):358-65. (United States study)

Beatrice conducted a prospective, non-blinded, observational study using a cross-sectional design and control cohorts in the U.S. The investigator assessed psychological adjustment and functioning (self-acceptance) in male-to-female patients with gender dysphoria (with and without gender reassignment surgery [GRS]), transvestites from two university specialty clinics, and self-identified heterosexual males recruited from the same two universities. The criteria to qualify for the study included being known to the clinic for at least one year, cross-dressing for at least one year without arrest, attendance at 10 or more therapy sessions, emotionally self-supporting, and financially capable of payment for reassignment surgery, and all of these criteria were met by the pre-operative cohort as well as the post-operative cohort. The cohorts were matched to the post-operative cohort (age, educational level, income, ethnicity, and prior heterosexual object choice). The post-operative cohort was selected not on the basis of population representation, but on the basis of demographic feasibility for a small study. The instruments used were the Minnesota Multiphasic Personality Inventory (MMPI) and the Tennessee Self-Concept Scale (TSCS). Changes or differences considered to be biologically significant were not pre-specified.

Of the initial 54 recruits, ten subjects were left in each of the cohorts because of exclusions identified due to demographic factors. The mean age of each cohort were as follows: pre-operative gender dysphoric patients 32.5 (range 27-42) years, postoperative patients 35.1 (30-43) years old, transvestite 32.5 (29-37) years old, and heterosexual male 32.9 (28-38) years old. All were Caucasian. The mean age for cross-dressing in pre-operative patients (6.4 years) and post-operative patients (5.8 years) was significantly lower than for transvestites (11.8 years).

The scores for self-acceptance did not differ by diagnostic category or surgical status as measured by the TSCS instrument. As measured by the T-scored MMPI instrument (50±10), levels of paranoia and schizophrenia were higher for post-operative (GRS) patients (63.0 and 68.8) than transvestites (55.6 and 59.6) and heterosexual males (56.2 and 51.6). Levels of schizophrenia were higher for pre-operative patients (65.1) than heterosexual males (51.6). There were no differences between patients with gender dysphoria by surgical status. Scores for the Masculine-Feminine domain were equivalent in those with transvestitism and gender dysphoria with or without surgery, but higher than in heterosexual males. The analysis revealed that despite the high level of socio-economic functioning in these highly selected subjects, the MMPI profiles based on the categories with the highest scores were notable for antisocial personality, emotionally unstable personality, and possible manic psychosis in the pre-operative GRS patients and for paranoid personality, paranoid schizophrenia, and schizoid personality in the post-operative GRS patients. By contrast, the same MMPI profiling in heterosexual males and transvestites was notable for the absence of psychological dysfunction.

Kraemer B, Delsignore A, Schnyder U, Hepp U. Body image and transsexualism. Psychopathology. 2008;41(2):96-100. Epub 2007 Nov 23.

Kraemer et al. conducted a prospective, non-blinded, observational study using a cross-sectional design comparing pre-and post-surgical cohorts. The investigators assessed body image, and patients were required to meet DSM III or DSM IV criteria as applicable to the time of entry into the clinic. Post-surgical patients were from a long-term study group (Hepp et al., 2002). Pre-surgical patients were recent consecutive referrals. The assessment tool was the Fragebogen zur Beurteilung des eigenen Korpers (FBeK) which contained 3 domains.

There were 23 pre-operative patients: 7 (30.4%) female-to-male and 16 (69.6%) male-to-female (ratio 1:2.3). There were 22 post-operative patients: 8 (36.4 %) female-to-male and 14 (63.6%) male-to-female (ratio 1:1.8). The mean ages of the cohorts were as follows: pre-operative 33.0±11.3 years; post-operative 38.2±9.0 years. The mean duration after reassignment surgery was 51±25 months (range 5-96).

The pre-operative groups had statistically higher insecurity scores compared to normative data for the natal sex: female-to-male 9.0±3.8 versus 5.1±3.7; male-to-female 8.1±4.5 versus 4.7±3.1 as well as statistically lower self-confidence in one’s attractiveness: female-to-male 3.1±2.9 versus 8.9±3.1; male-to-female 7.0±2.9 vs 9.5±2.6. Scores for insecurity and self-confidence in the post-operative cohort were not inferior to the normative values. Insecurity decreased statistically from 9.0±3.8 in the female-to-male pre-operative cohort and from 8.1±4.5 in the male-to-female pre-operative cohort to 4.4±3.8 and 3.4±2.3 in the respective post-operative cohorts. Self-confidence increased statistically from 3.1±2.9 in the female-to-male pre-operative cohort and 7.0±2.9 male-to-female pre-operative cohort to 9.29±1.98 and 10.29±2.0 in the respective post-operative cohorts.

d. Prospective, non-blinded, observational, cross-sectional studies with semi-matched controls

Kuhn A, Bodmer C, Stadlmayr W, Kuhn P, Mueller M, Birkhäuser M. Quality of life 15 years after sex reassignment surgery for transsexualism. Fertil Steril. 2009 Nov;92(5):1685-1689.e3. Epub 2008 Nov 6.

Kuhn et al. conducted a prospective, non-blinded, observational study using a cross-sectional design and semi-matched control cohort. The investigators assessed global satisfaction in patients who were from gynecology and endocrinology clinics, and who had undergone some aspect of gender reassignment surgery in the distant past, but were still receiving cross-sex hormones from the clinic. The quality-of-life assessment tools included a VAS and the King’s Health Questionnaire (KHQ) with its eight domains including one for incontinence. The KHQ questionnaire and the numerical change/difference required for clinical significance (≥5 points in a given domain, with higher scores being more pathologic) were included in the publication. Twenty healthy female controls from the medical staff who had previously undergone an abdominal or pelvic surgery were partially matched by age and body mass index (BMI), but not sex.

Of the 55 participants, three (5.4%) were female-to-male and 52 (94.5%) were male-to-female (ratio 1:17.3). Reassignment surgery had been conducted 8 to 23 years earlier (median 15 years). The median age of the patients at the time of the study was 51 years (range 39-62 years). The patients had undergone a median of 9 surgical procedures in comparison to the 2 undergone by controls. Patients were less likely to be married (23.6% versus 65%; p=0.002), and partnership status was unknown in 5 patients. The scores of VAS global satisfaction (maximal score 8) were lower for surgically reassigned patients (4.49±0.1 SEM) than controls (7.35±0.26 SEM) (p<0.0001).

There were statistically and biologically significant differences for 4 of the 8 domains between the patients and controls: physical limitation: 37.6±2.3 versus 20.9±1.9 (p0.0001), personal limitation: 20.9±1.9 versus 11.6±0.4 (p<0.001), role limitation: 27.8+2.4 versus 34.6+1.7 (p<0.5), and general health: 31.7±2.2 versus 41.0±2.3 (p<0.02). Information as to whether a high or low score was positive for the various domains was not provided. Wording from the abstract suggests that these 4 differences all reflected lower quality-of-life.

e. Prospective, blinded, observational, cross-sectional studies with no concurrent controls

Hess J, Rossi Neto R, Panic L, Rübben H, Senf W. Satisfaction with male-to-female gender reassignment surgery. Dtsch Arztebl Int. 2014 Nov 21;111(47):795-801.

Hess at al. conducted a prospective, blinded, observational study using a cross-sectional design and a self-designed questionnaire. The investigators assessed post-operative satisfaction in male-to-female patients with gender dysphoria who were followed in a urology specialty clinic. Patients had met the ICD-10 diagnostic criteria, undergone gender reassignment surgeries including penile inversion vaginoplasty, and a Likert-style questionnaire survey with 11 elements. Descriptive statistics were provided.

There were 254 consecutive eligible patients who had undergone surgery between 2004 and 2010 identified and sent surveys, of whom 119 (46.9%) responded anonymously. Of the participants, 13 (10.9%) reported dissatisfaction with outward appearance and 16 (13.4%) did not respond; three (2.5%) reported dissatisfaction with surgical aesthetics and 25 (21.0%) did not respond; eight (6.7%) reported dissatisfaction with functional outcomes of the surgery and 26 (21.8%) did not respond; 16 (13.4%) reported they could not achieve orgasm and 28 (23.5%) did not respond; four (3.4%) reported feeling completely male/more male than female and 28 (23.5%) did not respond; six (5.0%) reported not feeling accepted as a woman, two (1.7%) did not understand the question, and 17 (14.3%) did not respond; and 16 (13.4%) reported that life was harder and 24 (20.2%) did not respond.

Lawrence A. Patient-reported complications and functional outcomes of male-to-female sex reassignment surgery. Arch Sex Behav. 2006 Dec;35(6):717-27. Epub 2006 Nov 16. (United States study)

Lawrence conducted a prospective, blinded observational study using a cross-sectional design and a partially self-designed quality of life tool using yes/no questions or Likert scales. The investigator assessed sexual function, urinary function, and other pre/post-operative complications in patients who underwent male-to-female gender reassignment surgery. Questions addressed core reassignment surgery (neo-vagina and sensate neo-clitoris) and related reassignment surgery (labiaplasty, urethral meatus revision, vaginal deepening/widening, and other procedures), use of electrolysis, and use of hormones.

Questionnaires were designed to be completed anonymously and mailed to 727 eligible patients. Of those eligible, 232 (32%) returned valid questionnaires. The age at the time reassignment surgery was 44±9 (range 18-70) years and mean duration after surgery was 3±1 (range 1-7) years.

Happiness with sexual function and the reassignment surgery was reported to be lower when permanent vaginal stenosis, clitoral necrosis, pain in the vagina or genitals, or other complications such as infection, bleeding, poor healing, other tissue loss, other tissue necrosis, urinary incontinence, and genital numbness were present. Quality-of-life (QOL) was impaired when pain in the vagina or genitals was present.

Satisfaction with sexual function, gender reassignment surgery, and overall QOL was lower when genital sensation was impaired and when vaginal architecture and lubrication were perceived to be unsatisfactory. Intermittent regret regarding reassignment surgery was associated with vaginal hair and clitoral pain. Vaginal stenosis was associated with surgeries performed longer ago; whereas, more satisfaction with vaginal depth and width was present in more recent surgeries.

f. Prospective, non-blinded, observational, longitudinal and patients served as their own controls

Heylens G, Verroken C, De Cock S, T'Sjoen G, De Cuypere G. Effects of different steps in gender reassignment therapy on psychopathology: a prospective study of persons with a gender identity disorder. J Sex Med. 2014 Jan;11(1):119-26. Epub 2013 Oct 28.

Heylens et al. conducted a prospective, non-blinded observational study using a longitudinal design in which patients served as their own controls. They used a non-specific psychiatric test with normative data along with two self-designed questionnaires. The investigators assessed psychosocial adjustment and psychopathology in patients with gender identity disorders. Patients were to be sequentially evaluated prior to institution of hormonal therapy, then 3 to 6 months after the start of cross-sex hormone treatment, and then again one to 12 months after reassignment surgery. The Dutch version of the SCL-90R with 8 subscales (agorophobia, anxiety, depression, hostility, interpersonal sensitivity, paranoid ideation/psychoticism, and sleeping problems) and a global score (psycho-neuroticism) was used serially. A seven parameter questionnaire was used serially to assess changes in social function. Another cross-sectional survey assessed emotional state. The cohorts at each time point consisted of patients who were in the treatment cohort at the time and who had submitted survey responses.

Ninety of the patients who applied for reassignment surgery between June 2005 and March 2009 were recruited. Fifty seven entered the study. Forty six (51.1% of the recruited population) underwent reassignment surgery. Baseline questionnaire information was missing for 3 patients. Baseline SCL-90 scores were missing for 1 patient but included SCL-90 scores from some of the 11 recruits who had not yet undergone reassignment surgery. Time point 2 (after hormone therapy) SCL-90 information was missing for 10, but included SCL-90 scores from some of the 11 recruits who had not yet undergone reassignment surgery. At time point 3, 42 (91.3% of those who underwent reassignment surgery) patients completed some part of the SCL-90 survey and the psychosocial questionnaires. Some questionnaires were incomplete. The investigators reported response rates of 73.7% for the psychosocial questionnaires and 82.5% rates the SCL-90.

Of those who responded at follow-up after surgery, 88.1% reported having good friends; 52.4% reported the absence of a relationship; 47.6% had no sexual contacts; 42.9% lived alone; 40.5% were unemployed, retired, students, or otherwise not working; 2.4% reported alcohol abuse; and 9.3% had attempted suicide. The frequency of these parameters reportedly did not change statistically during the study interval, but there was no adjustment for the inclusion of patients who did not undergo surgery.

In a cross-sectional, self-report mood survey, of the 42 study entrants who completed the entire treatment regimen including reassignment surgery and the final assessment (refers to the initial 57) reported improved body-related experience (97.6%), happiness (92.9%), mood (95.2%), and self-confidence (78.6%) and reduced anxiety (81.0%). Of participants, 16.7% reported thoughts of suicide. Patients also reported on the intervention phase that they believed was most helpful: hormone initiation (57.9%), reassignment surgery (31.6%), and diagnostic-psychotherapy phase (10.5%).

The global “psycho-neuroticism” SCL-90R score, along with scores of 7 of the 8 subscales, at baseline were statistically more pathologic than the general population. After hormone therapy, the score for global “psycho-neuroticism” normalized and remained normal after reassignment surgery. More specifically the range for the global score is 90 to 450 with higher scores being more pathologic. The score for the general population was 118.3±32.4. The respective scores for the various gender dysphoric cohorts were 157.7±49.8 at initial presentation, 119.7±32.1 after hormone therapy, and 127.9±37.2 after surgery. The scores for the general population and the scores after either hormone treatment or surgical treatment did not differ.

Smith YL, Van Goozen SH, Kuiper AJ, Cohen-Kettenis PT. Sex reassignment: outcomes and predictors of treatment for adolescent and adult transsexuals. Psychol Med. 2005 Jan;35(1):89-99.

Smith et al. conducted a prospective, non-blinded, observational study using a longitudinal design and psychological function tools. Patients served as their own control prior to and after reassignment surgery. The investigator assessed gender dysphoria, body dissatisfaction, physical appearance, psychopathology, personality traits, and post-operative function in patients with gender dysphoria. Patients underwent some aspect of reassignment surgery. The test instruments included the Utrecht Gender Dysphoria Scale (12 items), the Body Image Scale adapted for a Dutch population (30 items), Appraisal of Appearance Inventory (3 observers, 14 items), the Dutch Short MMPI (83 items), the Dutch version of the Symptom Checklist (SCL)(90 items), and clinic-developed or modified questionnaires. Pre-treatment data was obtained shortly after the initial interview. Post-surgery data were acquired at least 1 year post reassignment surgery.

The size of the pool of available patients was not identified. Overall 325 consecutive adolescents and adults initially were “involved.” Of these, 103 (29 [28.2%] female-to-male patients and 74 [71.8%] male-to-female patients [ratio 1:2.6]) never started hormone therapy; 222 (76 [34.2%] female-to-male patients and 146 [65.8%] male-to-female patients [ratio 1:1.9]) initiated hormone therapy. Of the patients who started hormone therapy, 34 (5 [14.7%] female-to-male patients and 29 [85.3%] male-to-female patients [ratio 1:5.8]) discontinued hormone therapy. After discontinuation of hormone therapy, the study was limited to adults. Of adults, 162 (58 [35.8%] female-to-male and 104 [64.2%] male-to-female [ratio 1:1.8]) were eligible and provided pre-surgical test data, and 126 (77.8% of eligible adults) (49 [38.9%] female-to-male and 77 [61.1%] male-to-female [ratio 1:1.6]) provided post-surgical data. For those patients who completed reassignment, the mean age at the time of surgical request was 30.9 years (range 17.7-68.1) and 35.2 years (range 21.3-71.9) years at the time of follow-up. The intervals between hormone treatment initiation and surgery and surgery and follow-up were 20.4 months (range 12 to 73) and 21.3 months (range 12 to 47) respectively.

Of the 126 adults who provided post-surgical data, 50 (40.0%) reported having a steady sexual partner, three (2.3%) were retired, and 58 (46.0%) were unemployed. Regarding regret, six patients expressed some regret regarding surgery, but did not want to resume their natal gender role, and one male-to-female had significant regret and would not make the same decision.

Post-surgery Utrecht dysphoria scores dropped substantially and approached reportedly normal values. The patients’ appearance better matched their new gender. No one was dissatisfied with his/her overall appearance at follow-up. Satisfaction with primary sexual, secondary sexual, and non-sexual body traits improved over time. Male-to-female patients, however, were more dissatisfied with the appearance of primary sex traits than female-to-male patients. Regarding mastectomy, 27 of 38 (71.1%) female-to-male respondents (not including 11 non-respondents) reported incomplete satisfaction with their mastectomy procedure. For five of these patients, the incomplete satisfaction was because of scarring. Regarding vaginoplastly, 20 of 67 (29.8%) male-to-female respondents (not including 10 non-respondents) reported incomplete satisfaction with their vaginoplasty.

Most of the MMPI scales were already in the normal range at the time of initial testing. SCL global scores for psycho-neuroticism were minimally elevated before surgery 143.0±40.7 (scoring range 90 to 450) and normalized after surgery 120.3±31.4. (An analysis using patient level data for only the completers was not conducted.)

Megeri D, Khoosal D. Anxiety and depression in males experiencing gender dysphoria. Sexual and Relationship Therapy. 2007 Feb; 22(1):77-81. (Not in PubMed) and Udeze B, Abdelmawla N, Khoosal D, Terry T. Psychological functions in male-to-female people before and after surgery. Sexual and Relationship Therapy. 2008 May; 23(2):141-5. (Not in PubMed)

Udeze et al. conducted a prospective, non-blinded, longitudinal study assessing a randomized subset of patients who had completed a non-specific psychological function tool prior to and after male-to-female reassignment surgery. Patients served as their own controls. The investigators used the WPATH criteria for patient selection. Psychiatric evaluations were routine. All patients selected for treatment were routinely asked to complete the self-administered SCL-90R voluntarily on admission to the program and post-operatively. A post-operative evaluations (psychiatric and SCL-90R assessment) were conducted within 6 months to minimize previously determined loss rates. The patient pool was domestic and international. There were 546 gender dysphoric patients from all over the United Kingdom and abroad, of whom 318 (58.2%) progressed to surgery. Of these, 127 were from the local Leicester area in the United Kingdom and 38 (29.9%) progressed to surgery. The mean age for the selected male-to-female patients at the time of study was 47.33±13.26 years (range 25 to 80) and reflected an average wait time for surgery of 14 months (range 2 months to 6 years). For this investigation, 40 male-to-female subjects were prospectively selected.

The raw SCL-90 global scores for psycho-neuroticism were unchanged over time: 48.33 prior to surgery and 49.15 after surgery. If the scale was consistent with T-scoring, the results were non-pathologic. A statistical trend in the anger/hostility subscale was reported. No psychiatric disorders were otherwise identified prior to or after surgery.

Investigators from the same clinical group (Megeri, Khoosal, 2007) conducted additional testing to specifically address anxiety and depression with the Beck Depression Inventory, General Health Questionnaire (with 4 subscales), HADS, and Spielberger State and Trait Anxiety Questionnaire (STAI-X1 and STA-X2). The test population and study design appear to be the same. No absolute data were presented. Only changes in scores were presented. There were no statistically significant changes.

Kockott G, Fahrner EM. Transsexuals who have not undergone surgery: a follow-up study. Arch Sex Behav. 1987 Dec;16(6):511-22.

Kockott and Fahrner conducted a prospective, observational study using a longitudinal design. Treatment cohorts were used as controls, and patients served as their own controls. The investigators assessed psychosocial adjustment in patients with gender identity issues. Patients were to have met DSM III criteria. Trans-sexuality, transvestitism, and homosexuality were differentiated. The criteria required for patients to receive hormone therapy and/or reassignment surgery were not delineated. After receiving hormone therapy, patients were later classified by surgical reassignment status (pre-operative and post-operative) and desire for surgery (unchanged desire, hesitant, and no longer desired).

The first investigative tool was a semi-structured in-person interview consisting of 125 questions. The second investigative tool was a scale that organized the clinical material into nine domains which were then scored on a scale. The Psychological Integration of Trans-sexuals (PIT) instrument was not otherwise described in the publication or in other citations. There were 15 interviews and two separate interviewers. There were 80 patients identified, but 58 (72.5%) patients (26 pre-operative; 32 post-operative) were ultimately included in the analysis. The duration of follow-up was longer for post-operative patients (6.5 years) than for pre-operative patients (4.6 years) (including time for one patient subsequently excluded). The mean age of the post-operative patients was 35.5±13.1 years, and the age of the patients who maintained a continued desire for surgery was 31.7±10.2 years. The age of the patients who hesitated about surgery was somewhat older, 40.3±9.4 years. The age of the patients who were no longer interested in surgery was 31.8±6.5 years. All were employed or in school at baseline. Patients with hesitation were financially better-off, had longer-standing relationships even if unhappy, and had a statistical tendency to place less value on sex than those with an unchanged wish for surgery.

Post-operative patients more frequently reported contentment with the desired gender and the success of adaption to the gender role than the pre-operative patients with a persistent desire for surgery. Post-operative patients more frequently reported sexual satisfaction than pre-operative patients with a continuing desire for surgery. Post-operative patients also more frequently reported financial sufficiency and employment than pre-operative patients with a persistent desire for surgery. Suicide attempts were stated to be statistically less frequent in the post-surgical cohort.

Psychosocial adjustment scores were in the low end of the range with “distinct difficulties” (19-27) at the initial evaluation for the post-operative patients (19.7), the pre-operative patients with a persistent wish for surgery (20.2), and the hesitant patients (19.7). At initial evaluation, psychosocial adjustment scores for patients no longer wanting surgery were at the high end of the range with “few difficulties” (10-18). At the final evaluation, Psychosocial adjustment scores were at the high end of the range “few difficulties” (10-18) for the post-operative patients (13.2) and the patients no longer wanting surgery (16.5). Psychosocial adjustment scores at the final evaluation were in the borderline range between “few difficulties” (10-18) and “distinct difficulties” (19-27) for both the pre-operative patients with a persistent desire for surgery (18.7), and the hesitant patients (19.1).

The changes in the initial score and the final follow-up score within e ach group were tracked and reported to be statistically significant for the post-operative group, but not for the other groups. Statistical differences between groups were not presented. Moreover, the post-operative patients had an additional test immediately prior to surgery. The first baseline score (19.7) would have characterized the patients as having “distinct difficulties” in psychosocial adjustment while the second baseline score (16.7) would have categorized the patients as having “few difficulties” in psychosocial adjustment despite the absence of any intervention except the prospect of having imminent reassignment surgery. No statistics reporting on the change between scores of the initial test and the test immediately prior to surgery and the change between scores of the test immediately prior to surgery and the final follow-up were provided.

g. Prospective, non-blinded, observational, longitudinal study with retrospective baseline data

Meyer JK, Reter DJ. Sex reassignment. Follow-up. Arch Gen Psychiatry. 1979 Aug;36(9):1010-5. (United States study)

Meyer and Reter conducted a prospective, non-blinded, observational study using a longitudinal design and retrospective baseline data. Interview data were scored with a self-designed tool. There were treatment control cohorts, and patients served as their own controls. The investigators assessed patients with gender dysphoria. The 1971 criteria for surgery required documented cross-sex hormone use as well as living and working in the desired gender for at least 1 year in patients subsequently applying for surgery. Clinical data including initial interviews were used for baseline data. In follow-up, the investigators used extensive 2 to 4 hour interviews to collect information on (a) objective criteria of adaptation, (b) familial relationships and coping with life milestones, and (c) sexual activities and fantasies. The objective criteria, which were the subject of the publication, included employment status (Hollingshead job level), cohabitation patterns, and need for psychiatric intervention. The investigators designed a scoring mechanism for these criteria and used it to determine a global adjustment score.

The clinic opened with 100 patients, but in follow-up, 52 of the 100 patients were interviewed and 50 of the interviewees gave consent for publication. Of these, 15 (4 female-to-male, 11 male-to-female; ratio 1:2.8) were part of the initial operative cohort, 14 (1 female-to-male; 13 male-to-female; ratio 1:13) later underwent reassignment surgery at the institution or elsewhere, and 21 (5 female-to-male; 16 male-to-female; ratio 1:3.2) did not undergo surgery. The mean ages of these cohorts were 30.1, 30.9, and 26.7 years respectively. The mean follow-up time was 62 months (range 19-142) for those who underwent surgery and 25 months (range 15-48) for those who did not. Socioeconomic status was lowest in those who subsequently underwent reassignment surgery.

Of patients initially receiving surgery, 8% had some type of later psychiatric contact, which was approximately 3.5 times higher in those who had not under gone surgery or who had done so later. There was a single female-to-male patient with multiple surgical complications who sought partial reassignment surgery reversal.

The adjustment scores improved over time with borderline statistical significance for the initial operative group and with statistical significance for the never operated group. Both the absolute score value at follow-up and the magnitude of change were the same. By contrast, the adjustment scores did not improve for those who were not in the cohort initially approved for surgery, but who subsequently underwent surgery later. This was particularly true if the surgery was performed elsewhere.

h. Prospective, non-blinded, observational, semi-cross sectional with no controls

Johansson A, Sundbom E, Höjerback T, Bodlund O. A five-year follow-up study of Swedish adults with gender identity disorder. Arch Sex Behav. 2010 Dec;39(6):1429-37. Epub 2009 Oct 9.

Johansson et al. conducted non-blinded, observational study using a semi-cross-sectional design (albeit over an extended time interval) using a self-designed tool and Axis V assessment. The study was prospective except for the acquisition of baseline Axis V data. There were no formal controls in this mixed population with and without surgery.

The investigators assessed satisfaction with the reassignment process, employment, partnership, sexual function, mental health, and global satisfaction in gender-reassigned persons from two disparate geographic regions. No other information regarding the sites of care was provided. Surgical candidates were required to have met National Board of Health and Welfare criteria including initial and periodic psychiatric assessment, ≥1 year of real-life experience in preferred gender, and ≥1 year of subsequent hormone treatment. In addition, participants were required to have been approved for reassignment 5 or more years prior and/or to have completed surgical reassignment (e.g., sterilization, genital surgery) 2 or more years prior. The investigators employed semi-structured interviews covering a self-designed list of 55 pre-formulated questions with a 3 or 5 point ordinal scale. Clinician assessment of Global Assessment of Functioning (GAF; Axis V) was also conducted and compared to initial finding during the study. Changes or differences considered to be biologically significant were not pre-specified. Diagnostic cut points were not provided. Statistical corrections for multiple comparisons were not included. There was no stratification by treatment.

Of the pool of 60 eligible patients, there were 21 (35.0%) female-to-male and 39 (65%) male-to-female (ratio 1:1.9) ; 32 (53.3% of eligible) (14 [43.8%] female-to-male; 18 [56.2%] male-to-female [ratio 1:1.3]) had completed genital gender reassignment surgery (not including 1 post mastectomy), 5 were still in the process of completing surgery, and 5 (1 female-to-male; 4 male-to-female; ratio 1:4) had discontinued the surgical process prior to castration and genital surgery.

The ages of the patients (ranges) at entry into the program, reassignment surgery, and follow-up were 27.8 (18-46), 31.4 (22-49), and 38.9 (28-53) in the female-to-male group respectively and 37.3 (21-60), 38.2 (22-57), and 46.0 (25.0-69.0) in the male-to-female group respectively. The differences in age by cohort group were statistically significant. Of participants, 88.2% of all enrolled female-to-male versus 44.0% of all enrolled female-to-male patients had cross-gender identification in childhood (versus during or after puberty) (p<0.01).

Although 95.2% of all enrolled patients self-reported improvement in GAF, in contrast, clinicians determined GAF improvement in 61.9% of patients. Clinicians observed improvement in 47% of female-to-male patients and 72% of male-to-female patients. A ≥5 point improvement in the GAF score was present in 18 (42.9%). Of note, three of the five patients who were in the process of reassignment and five of the five who had discontinued the process were rated by clinicians as having improved.

Of all enrolled 95.2% (with and without surgery) reported satisfaction with the reassignment process. Of these patients, 33 (79%) identified themselves by their preferred gender and nine (21%) identified themselves as transgender. None of these nine (eight male-to-female) had completed reassignment surgery because of ambivalence secondary to lack of acceptance by others and dissatisfaction with their appearance. Of the patients who underwent genital surgery (n=32) and mastectomy only (n=1), 22 (66.7%) were satisfied while four (three female-to-male) were dissatisfied with the surgical treatment.

Regarding relationships after surgery, 16 (38%) (41% of female- to-male; 36% of male-to-female) were reported to have a partner. Yet more than that number commented on partner relationships: 62.2 % of the 37 who answered (50.0% of female- to-male; 69.6% of male-to-female) reported improved partner relationships (5 [11.9%] declined to answer.); 70.0% of the 40 who answered (75.0% of female-to-male; 66.7% of male-to-female) reported an improved sex life. Investigators observed that reported post-operative satisfaction with sex life was statistically more likely in those with early rather than late cross-gender identification.

In addition 55.4% self-reported improved general health; 16.1% reported impaired general health; 11.9% were currently being treated with anti-depressants or tranquilizers; 44.7 % of the 38 who answered (53.3% of female-to-male; 39.1% of male-to-female) reported improved work circumstances (4 [9.5%] declined to answer.); 61.9% were students or employed. The remainder (38.1%) were living on disability pensions (28.6%), unemployed (4.8%), or retired (4.8%).

i. Prospective, cross sectional, observational, internet self- report survey, with unknown blinding, no formal controls

Newfield E, Hart S, Dibble S, Kohler L. Female-to-male transgender quality of life. Qual Life Res. 2006 Nov;15(9):1447-57. Epub 2006 Jun 7. (United States study)

Newfield et al. conducted a prospective, observational internet self-report survey of unknown blinding status using a cross-sectional design and a non-specific quality of life tool in a mixed, population with and without reassignment surgery. There were no formal controls.

The investigators recruited natal female participants identifying as male using email, internet bulletin boards, and flyers/postcards distributed in the San Francisco Bay Area. Reduction of duplicate entries by the same participant was limited to the use of a unique user name and password.

The investigators employed the SF-36 Version 2 using U.S. normative data. They reported using both male and female normative data for the comparator SF-36 cohort. Data for the 8 domains were expressed as normative scoring. The Bonferroni correction was used to adjust for the risk of a Type 1 error with analyses using multiple comparisons.

A total of 379 U.S. respondents classified themselves as males or females to males with or without therapeutic intervention. The mean age of the respondents who classified themselves as male or female-to-male was 32.6±10.8 years. 89% were Caucasian, 3.6% Latino, 1.8% African American, 1.8% Asian, and 3.8% other. 254 (67.0%) reported any testosterone use in the past or currently; and 242 (63.8%) reported current testosterone use. In addition, 136 (36.7%) reported having had “top” surgery and 11 (2.9%) reported having “bottom” surgery. The Physical Summary Score (53.45±9.42) was statistically higher (better) than the natal gender unspecified SF-36 normative score (50±10) (p=<0.001), but was within 1 standard deviation of the normative mean. The Mental Summary Score (39.63±12.2) was statistically lower (worse) than the natal gender unspecified SF-36 normative score (50±10) (p<0.001), but was well within 2 standard deviations of the normative mean. Subcomponents of this score: Mental Health (42.12±10.2), Role Emotional (42.42±11.6), Social Functioning (43.14±10.9), and Vitality (46.22±9.9) were statistically lower (worse) than the SF-36 normative sub-scores, but well within 1 standard deviation of the normative sub-score means. Interpretive information for these small biologic differences in a proprietary assessment tool was not provided.

Additional intragroup analyses were conducted, although the data were not stratified by type of therapeutic intervention (hormonal, as well as, surgical). Outcomes of hormone therapy were considered separately and dichotomously from reassignment surgery. The Mental Summary Score was statistically higher (better) in those who had “Ever Received Testosterone” (41.22±11.9) than those with “No Testosterone Usage” (36.08±12.6) (p=0.001). The Mental Summary Scores showed a trend towards statistical difference between those who “Ever Received Top Surgery” (41.21±11.6) and those without “Top Surgery” (38.01±12.5) (p=0.067). These differences were well within 1 standard deviation of the normative mean. Interpretive information for these small biologic differences in a proprietary assessment tool was not provided.

j. Partially prospective, non-blinded, observational studies with longitudinal designs and patients served as their own controls

Ruppin U, Pfäfflin F. Long-term follow-up of adults with gender identity disorder. Arch Sex Behav. 2015 Jul;44(5):1321-9. Epub 2015 Feb 18.

Ruppin and Pfafflin conducted a partially prospective, non-blinded, observational study using a longitudinal design and non-specific psychometric tests and a self-designed interview tool and questionnaire. Patients served as their own controls.

The investigators assessed psychological symptoms, interpersonal difficulties, gender role stereotypes, personality characteristics, societal function, sexual function, and satisfaction with new gender role in patients with gender dysphoria. Patients were required to have met the ICD-10 criteria for trans-sexualism, been seen by the clinic by prior to 2001, and completed an official change in gender including name change prior to 2001. Assessment tools included German versions of standardized surveys with normative data: the SCL 90R, the Inventory of Interpersonal Problems (IIP), Bem Sex Role Inventory (BSRI), and the Freiburg Personality Inventory (FPI-R), along with semi-structured interviews with self-designed questionnaires. The prospective survey results were compared to retrospective survey results.

Overall, 140 patients received recruitment letters then 71 (50.7%) agreed to participate. Of these participants, 36 (50.7%) were female-to-male; 35 (49.3%) were male-to-female (ratio 1:0.97). The ages of the patients were: 41.2±5.78 years female-to-male and 52.9±10.82 years male-to-female 52.9±10.82 years. The intervals for follow-up were 14.1±1.97 years and 13.7±2.17 years respectively.

All female-to-male patients had undergone mastectomy; 91.7% had undergone oopherectomy and/or hysterectomy; 61.1% had undergone radial forearm flap phalloplasty or metaoidioplasty; 94.3% of male-to-female patients had undergone vaginoplasty and perhaps an additional procedure (breast amplification, larynx surgery, or vocal cord surgery). Two male-to-female patients had not undergone any reassignment surgery, but were still included in the analyses.

A total of 68 patients ranked their well-being as 4.35±0.86 out of five (three patients did not respond to this question). Of respondents, 40% reported not in a steady relationship. Regular sexual relationships were reported by 57.1% of 35/36 female-to-male respondents and 39.4% of 33/35 of male-to-female respondents (three patients did not respond to this question). A total of 11 patients reported receiving out-patient psychotherapy; 69 did not express a desire for gender role reversal (two did not respond to this question). The response rate was less than 100% for most of the self-designed survey questions.

Changes from the initial visit to the follow-up visit were assessed for the SCL-90R in 62 of 71 patients. Changes from the initial visit to the follow-up visit were assessed for the IIP in 55 of 71 patients. Changes from the initial visit to the follow-up visit were assessed for the FPI-R in 58 of 71 patients. The effect size was large only for the “Life Satisfaction” scale. Changes from the initial visit to the follow-up visit were assessed for the BSRI in 16 of 36 female-to-male patients and 19 of 35 male-to-female patients. The “Social Desirability” score increased for the female-to-male respondents. At endpoint, both categories of respondents reported androgynous self-images.

k. Partially prospective, non-blinded, observational studies with cross-sectional designs that had control groups but were not concurrent

Haraldsen IR, Dahl AA. Symptom profiles of gender dysphoric patients of transsexual type compared to patients with personality disorders and healthy adults. Acta Psychiatr Scand. 2000 Oct;102(4):276-81.

Haraldsen and Dahl conducted a partially prospective, non-blinded, observational study using a cross-sectional design and a non-specific psychometric test. There was a control group, but it was not concurrent.

In the germane sub-study, the investigator assessed psychopathology in patients with gender dysphoria. Patients, who were independently evaluated by 2 senior psychiatrists, were required to meet DSM III-R or DSM IV diagnostic criteria and the Swedish criteria for reassignment surgery. The Norwegian version of the SCL-90 was used. The testing was conducted from 1987 to 1989 for those who had undergone reassignment surgery between 1963 and 1987 and from 1996 to 1998 for pre-surgical patients who had applied for reassignment surgery between 1996 and 1998. In addition, Axis I, Axis II, and Axis V (Global Functioning) was assessed.

Of 65 post–surgical and 34 pre-surgical patients, 59 post-surgical and 27 pre-surgical patients ultimately entered the study. The combined cohorts consisted of 35 (40.7%) female-to-male patients and 51 (59.3%) male-to-female patients (ratio 1:1.5). The ages were female-to-male 34±9.5 years and female-to-male 33.3±10.0 years. The other control group consisted of patients with personality disorder. 101 (27 men (33.9±7.3 years) and 74 women (31.6±8.2) were tested during a treatment program. One year later, 98% were evaluated.

A total of 28 (32.5%) of the pre- and post- reassignment surgery patients had an Axis I diagnosis compared to 100 (99.0%) of those with personality disorders. Depression and anxiety were the most common diagnoses in both groups, but were approximately three to four times more common in the personality disorder cohort. Seventeen (19.8%) of the pre- and post- reassignment surgery patients had an Axis II diagnosis whereas the mean number of personality disorders in the personality disorder cohort was 1.7±1. The Global Assessment of Function was higher (better) in the gender dysphoric groups 78.0±8.9 than in the personality disorder cohort (53.0±9.0).

Global Severity Indices (GSI) were highest for those with personality disorder regardless of gender and exceeded the cut-point score of 1.0. The GSI scores for females-to-males and males-to-females were 0.67±57 and 0.56±0.45. Although they were nominally higher than the healthy normative controls (males: 0.32±0.36 and females 0.41±0.43), they were well within the non-pathologic range. The same was true for the subscales.

SCL-90 GSI scores did not differ substantively between pre- and post-surgical patients, nor did the SCI subscale scores differ substantively between pre- and post-surgical patients. Any small non-significant differences tracked with the age and sex differences.

l. Partially prospective, non-blinded, observational studies with cross-sectional designs that had no control groups

Leinung M, Urizar M, Patel N, Sood S. Endocrine treatment of transsexual persons: extensive personal experience. Endocr Pract. 2013 Jul-Aug;19(4):644-50. (United States study)

Leinung et al. conducted a partially prospective, non-blinded, observational study using a cross-sectional design and descriptive statistics. There were no formal controls. The investigators assessed employment, substance abuse, psychiatric disease, mood disorders, Human Immunodeficiency Virus (HIV) status in patients who had met WPATH guidelines for therapy, and who had initiated cross-sex hormone treatment.

A total of 242 patients treated for gender identity disorder in the clinic from 1992 through 2009 inclusive were identified. The number of those presenting for therapy almost tripled over time. Of these patients, 50 (20.7%) were female-to-male; 192 (79.3%) male-to-female (ratio 1:3.8).

The age of female-to-male and male-to-female patients with gender dysphoria at the time of clinic presentation was 29.0 and 38.0 years respectively.

The female-to-male and male-to-female patients with gender dysphoria at the time of hormone initiation were young: 27.5 and 35.5 years old respectively (p<0.5). Of the male-to-female cohort, 19 (7.8%) had received hormone therapy in the absence of physician supervision; 91 (37.6%) had undergone gender-reassignment surgery (32 female-to-male [64.0% of all female-to-male; 35.2% of all surgical patients]; 59 male-to-female [30.7% of all male-to-female; 64.8% of all surgical patients]; ratio 1:1.8).

Psychiatric disease was more common in those who initiated hormone therapy at an older age (>32 years) 63.9% versus 48.9% at a younger age and by natal gender (48.0% of female-to-male; 58.3% male-to-female). Mood disorders were more common in those who initiated hormone therapy at an older age (>32 years) 52.1% versus 36.0% at a younger age and this finding did not differ by natal gender (40.0% of female-to-male; 44.8% male-to- female). The presence of mood disorders increased the time to reassignment surgery in male-to-female patients. Of participants 36.4% were employed in jobs requiring a high school degree or less; 28.1% (excluding students) were on disability and/or unemployed. Rates of disability and unemployment were higher in male-to-female patients (31.8%) than female-to-male patients (14.0%). Mental health diagnoses reportedly were the major reason for disability. HIV infection and substance abuse were higher in male-to-female patients than female-to-male patients (8.3% versus 0% and 12.5% versus 6.0% respectively).

m. Retrospective, non-blinded, observational, longitudinal studies

Asscheman H, Giltay EJ, Megens JA, de Ronde WP, van Trotsenburg MA, Gooren LJ. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2011 Apr;164(4):635-42. Epub 2011 Jan 25.

Asscheman et al. conducted a retrospective, non-blinded, observational study of mortality using a longitudinal design of population treated with hormones, as well as, reassignment surgery and a population-based cohort. The investigators assessed mortality in patients who (a) were from a single-center, unspecified, university specialty clinic, (b) initiated cross-sex hormone treatment prior to July 1, 1997, and (c) had been followed by the clinic for at least 1 year or had expired during the first year of treatment. The National Civil Record Registry (Gemeentelijke Basis Administratie) was used to identify/confirm deaths of clinic patients. Information on the types or hormones used was extracted from clinic records, and information on the causation of death was extracted from medical records or obtained from family physicians. Mortality data for the general population was obtained through by the Central Bureau of Statistics of the Netherlands. Mortality data from Acquired Immune Deficiency Syndrome (AIDS) and substance abuse were extracted from selected Statistics Netherlands reports. The gender of the general Dutch population comparator group was the natal sex of the respective gender dysphoric patient groups.

A total of 1,331 patients who met the hormone treatment requirements were identified (365 female-to-male [27.4%]; 966 male-to-female [72.6%]; ratio 1:2.6). Of these, 1,177 (88.4%) underwent reassignment surgery (343 [94.0% of female-to-male entrants]; 834 [86.3% of male-to-female entrants]; ratio 1:2.4; p<0.0001). The mean age at the time of hormone initiation in female-to-male and male-to-female patients was young: 26.1±7.6 (range 16–56) years and 31.4±11.4 (range 16–76) years respectively, although the male-to-female subjects were relatively older (p<0.001). The mean duration of hormone therapy in female-to-male and male-to-female patients was 18.8±6.3 and 19.4±7.7 years respectively.

There were a total of 134 deaths in the clinic population using hormone therapy as well as reassignment surgery. Of the patients, 12 (3.3%) of the 365 female-to-male patients and 122 (12.6%) of the 966 male-to-female patients died. All-cause mortality was 51% higher and statistically significant (Standardized Mortality Ratio [SMR] 95% confidence interval [CI]) 1.47-1.55) for males-to-females when compared to females in the general Dutch population. The small increase in all-cause mortality (12%) for females-to-males when compared to males in the general Dutch population was not statistically significant; 95% CI 0.87-1.42.

The major known contributors to the mortality difference between male-to-female patients and the Dutch population at large were completed suicide (n=17, SMR 5.70 [95% CI 4.93-6.54]), AIDS (n=16, SMR 30.20 [95% CI 26.0-34.7), and illicit drug use (n=5, SMR 13.20 [95% CI 9.70-17.6]). An additional major contributor was “unknown cause” (n=21, SMR 4.00 [95% CI 3.52-4.51]). Of the 17 male-to-female hormone treated patients who committed suicide, 13 (76.5%) had received prior psychiatric treatment and 6 (35.3%) had not undergone reassignment surgery because of concerns about metal health stability.

Ischemic heart disease was a major disparate contributor to excess mortality in male-to-female patients in older patients (n=18, SMR 1.64 [95% CI 1.43-1.87], mean age [range]: 59.7 [42-79] years. Current use of aparticular type of estrogen, ethinyl estradiol, was found to contribute to death from myocardial infarction or stroke (Adjusted Hazard Ratio 3.12 [95% CI 1.28-7.63), p=0.01). There was a smaller, but statistically significant increase in lung cancer that was thought to possibly be related to higher rates of smoking in this cohort.

Although overall mortality was not increased in the hormone-treated female-to-male patients, there were more deaths due to illicit drug use than expected (SMR 25 [6.00-32.5]).

n. Retrospective, non-blinded, observational, longitudinal studies using matched national data

Dhejne C, Lichtenstein P, Boman M, Johansson A, Långström N, Landén M. Long-term follow-up of transsexual persons undergoing sex reassignment surgery: cohort study in Sweden. PLoS One. 2011;6(2):e16885. Epub 2011 Feb 22.

Dhejne et al. conducted a retrospective, non-blinded, observational study of nation-wide mortality using a longitudinal and a population-based matched cohort. The investigators assessed mortality, suicide attempts, psychiatric hospitalization, and substance abuse in gender-reassigned persons and randomly selected unexposed controls matched by birth year and natal sex (1:10) as well as by birth year and the reassigned gender (1:10). Data were extracted from national databases including the Total Population Register (Statistics Sweden), the Medical Birth Register, the Cause of Death Register (Statistics Sweden), the Hospital Discharge Register (National Board of Health and Welfare), the Crime Register (National Council of Crime), and those from the Register of Education for highest educational level. The criteria required to obtain the initial certificate for reassignment surgery and change in legal status from the National Board of Health and Welfare were not delineated, but included evaluation and treatment by one of 6 specialized teams, name change, a new national identity number, continued use of hormones, and sterilization/castration. Descriptive statistics with hazard ratios were provided. There were 804 patients identified with gender identity disorder (or related disorder) in Sweden during the period from 1973 to 2003 inclusive. Of these patients, 324 (40.3%) underwent gender-reassignment surgery (133 female-to-male [41.0%]; 191 male-to-female [59.0%]; ratio 1:1.4). The average follow-up time for all-cause mortality was 11.4 years (median 9.1). The average follow-up time for psychiatric hospitalization was 10.4 years (median 8.1).

The mean ages in female-to-male and male-to-female reassigned patients were: 33.3±8.7 (range 20–62) and 36.3± 10.1 (range 21–69) respectively. Immigrant status was two times higher in reassigned patients (n=70, 21.6%) than in either type of control (birth [natal] sex matched n=294 [9.1%] or reassigned gender matched n=264 [8.1%]). Educational attainment (10 or more years) was somewhat lower for reassigned patients (n=151 [57.8%]) than in either type of control (birth sex matched n=1,725 [61.5%] or reassigned gender matched n=1804 [64.3%]) (cohort data were incomplete). The biggest discordance in educational attainment was for female-to-male reassigned patients regardless of the control used. Prior psychiatric morbidity (which did not include hospitalization for gender dysphoria) was more than four times higher in reassigned patients (n=58, 17.9%) than in either type of control (birth sex matched n=123 [3.8%] or reassigned gender matched n=114 [3.5%]).

All-cause mortality was higher for patients who underwent gender reassignment surgery (n=27 [8.3%]) than in controls (hazard ratio 2.8 [1.8-4.3]) even after adjustment for covariants (prior psychiatric morbidity and immigration status). Divergence in the survival curves began at 10 years. The major contributor to this mortality difference was completed suicide (n=10 [3.1%]; adjusted hazard ratio 19.1 [5.8-62.9]). Mortality due to cardiovascular disease was modestly higher for reassigned patients (n=9 [2.8%]) than in controls (hazard ratio 2.5 [1.2-5.3]).

Suicide attempts were more common in patients who underwent gender reassignment surgery (n= 29 [9.0%] than in controls (adjusted hazard ratio 4.9 [2.9–8.5]). Male- to-female patients were at higher adjusted risk for attempted suicide than either control whereas female-to-male patients were at higher adjusted risk compared to only male controls and maintained the female pattern of higher attempted suicide risk. Hospitalizations for psychiatric conditions (not related to gender dysphoria) were more common in reassigned persons n= 64 [20.0%] than in controls (hazard ratio 2.8 [2.0–3.9]) even after adjusting for prior psychiatric morbidity. Hospitalization for substance abuse was not greater than either type of control. The increased risk for conviction of any crime or violent crime observed during the 1973-1988 interval was not seen later.

Dhejne C, Öberg K, Arver S, Landén M. An analysis of all applications for sex reassignment surgery in Sweden, 1960-2010: prevalence, incidence, and regrets. Arch Sex Behav. 2014 Nov;43(8):1535-45. Epub 2014 May 29 and Landén M, Wålinder J, Hambert G, Lundström B. Factors predictive of regret in sex reassignment. Acta Psychiatr Scand. 1998 Apr;97(4):284 (Dhejne et al., 2014; Landen et al., 1998) Sweden-All

Dhejne et al. conducted a non-blinded, observational study that was longitudinal for the capture of patients with “regret” in a national database. This same group (Landen et al., 1998) conducted a similar study along with retrospective acquisition of clinical data to explore the differences between the cohorts with and without regret. There were no external controls; only intra-group comparisons for this surgical series.

The investigators assessed the frequency of regret for gender reassignment surgery. Data were extracted from registries at the National Board of Health and Welfare to which patients seeking reassignment surgery or reversal of reassignment surgery make a formal application and which has maintained such records since a 1972 law regulating surgical and legal sex reassignment. The investigators reviewed application files from 1960 through 2010. The specific criteria to qualify for gender surgery were not delineated. Patients typically underwent diagnostic evaluation for at least 1 year. Diagnostic evaluation was typically followed by the initiation of gender confirmation treatment including hormonal therapy and real-life experience. After 2 years of evaluation and treatment, patients could make applications to the national board. Until recently sterilization or castration were the required minimal surgical procedures. (Dhejne et al., 2011) Secular changes in this program included consolidation of care to limited sites, changes in accepted diagnostic criteria, and provision of non-genital surgery, e.g., mastectomy during the real-life experience phase, and family support.

Of the 767 applicants for legal and surgical reassignment (289 [37.7%] female-to-male and 478 [62.3%] male-to-female; ratio 1:1.6]. The number of applicants doubled each ten year interval starting in 1981.

Of the applicants, 88.7% or 681 (252 [37.0%] female-to-male and 429 [63.0%] male-to-female; ratio 1:1.7] had undergone surgery and changed legal status by June 30, 2011. This number included eight (four [50.0%] female to-male and four [50.0%] male to female; ratio 1:1) people who underwent surgery prior to the 1972 law. (This number [6.0%] appears to include 41 (two [4.9%] female-to-male and 39 [95.1%] male-to-female; ratio 1:19.5) people who underwent surgery abroad at their own expense [usually in Thailand or the U.S.]. This cohort includes one person who was denied reassignment surgery by Sweden.)

Twenty-five (3.3%) of the applications were denied with the two most common reasons being an incomplete application or not meeting diagnostic criteria. An additional 61(8.0%) withdrew their application, were wait-listed for surgery, postponed surgery (perhaps in hopes of the later revocation of the sterilization requirement), or were granted partial treatment.

The formal application for reversal of the legal gender status, the “regret rate”, was 2.2%. No one who underwent sex-reassignment surgery outside of Sweden (36 of 41 after 1991) has requested reversal. The authors noted, however, that this preliminary number may be low because the median time interval to reversal request was eight years-only three of which had elapsed by publication submission- and because it was the largest serial cohort. This number did not include other possible expressions of regret including suicide (Dhejne et al., 2011).

Dhejne et al. in 2014 reported that the female-to-male: male-to-female ratio among those who made formal applications for reversal was 1:2. The investigators also reported that the female-to-male applicants for reversal were younger than the entire female-to-male cohort (median age 22 versus 27 years) while the male-to-female applicants for reversal were older than the entire male-to-female cohort (median age 35 versus 32 years). Other clinical data to explore the differences between the cohorts with and without regret were not presented in this update publication.

In their earlier publication, in addition to determining a regret rate (3.8%), Landen et al. extracted data from medical records and government verdicts. Logistic regression analyses were used identify relationships between variables. They observed that: (a) 25.0% of the cohort with regrets and 11.4% of the cohort without regrets were unemployed, (b) 16.7% of the cohort with regrets and 15.4% of the cohort without regrets were on “sick benefit”, (c) 15.4% of the cohort with regrets and 13.9% of the cohort without regrets had problems with substance abuse, (d) 69.2% of the cohort with regrets and 34.6% of the cohort without regrets had undergone psychiatric treatment, (e) 15.4% of the cohort with regrets and 8.8% of the cohort without regrets had a mood disorder, and (f) 15.4% of the cohort with regrets and 1.5% of the cohort without regrets had a psychotic disorder.

The putative prognostic factors that were statistically different (albeit without Bonferroni correction) between the cohorts with and without regret included prior psychiatric treatment, a history of psychotic disorder, atypical features of gender identity, and poor family support. Factors that trended towards statistical difference included having an unstable personality, sexual orientation and transvestitism. These variables were tested with logistic regression. Initial modeling included the variable “history of psychotic disorder”. Although this variable was predictive, it was excluded from future analyses because it was already a contraindication to reassignment surgery. Additional analyses identified poor family support as the most predictive variable and atypical features of gender identity as the second most important variable. Presence of both variables has a more than additive effect.

The nationwide mortality studies by Dhejne et al. 2011 includes much, if not all, of the Landen (1998) patient population and most of the Dhejne (2014) population.

o. Randomized, non-blinded, longitudinal, some patients served as their own controls

Mate-Kole C, Freschi M, Robin A. A controlled study of psychological and social change after surgical gender reassignment in selected male transsexuals. Br J Psychiatry. 1990 Aug;157:261-4.

Mate-Kole at al. conducted a prospective, non-blinded, controlled, randomized, longitudinal study using investigator-designed patient self-report questionnaires and non-specific psychological tests with some normative data. The investigators assessed neuroticism and sex role in natal males with gender dysphoria who had qualified for male-to-female reassignment surgery at a single-center specialty clinic. Forty sequential patients were alternately assigned to early reassignment surgery or to standard wait times for reassignment surgery. Patients were evaluated after acceptance and 2 years later. The criteria used to qualify for gender surgery were the 1985 standards from the Harry Benjamin International Gender Dysphoria Association. These included a ≥2 year desire to change gender, a ≥1 year demonstrable ability to live and be self-supporting in the chosen gender, and psychiatric assessment for diagnosis and reassessment at 6 months for diagnostic confirmation and exclusion of psychosis. Reassignment surgery was defined as orchidectomy, penectomy, and construction of a neo-vagina. The instruments used were the CCEI for psychoneurotic symptoms and the Bem Sex Role Inventory along with an incompletely described investigator-designed survey with questions about social life and sexual activity. The mean age and range of the entire cohort was 32.5 years (21-53).

Members of the early surgery cohort had a history of attempted suicide (one patient), psychiatric treatment for non-gender issues (six patients), and first degree relatives with psychiatric histories (four patients). Members of the standard surgery cohort were similar, with a history of attempted suicide (two patients), psychiatric treatment for non-gender issues (five patients), and first degree relatives with psychiatric histories (six patients). The early surgery group had surgery approximately 1.75 years prior to the follow-up evaluation. In both groups, cross-dressing began at about age 6.

At baseline, the Bem Sex Role Inventory femininity scores were slightly higher than masculinity scores for both cohorts and were similar to Bem North American female normative scores. The scores did not change in either group over time.

At baseline, the scores for the CCEI individual domains (free floating anxiety, phobic anxiety, somatic anxiety, depression, hysteria, and obsessionality) were similar for the cohorts. The total CCEI scores for the two cohorts were consistent with moderate symptoms. Over the 2 year interval, total CCEI scores increased for standard wait group and approached the relatively severe symptom category. During the same interval, scores dropped into the asymptomatic rage for the post-operative patients.

The investigator-designed survey assessed changes in social and sexual activity of the prior 2 years, but the authors only compared patients in a given cohort to themselves. Though the researchers did not conduct statistical studies to compare the differences between the 2 cohorts, they did report increased participation in some, but not all, types of social activities such as sports (solo or group), dancing, dining out, visiting pubs, and visiting others. Sexual interest also increased. By contrast, pre-operative patients did not increase their participation in these activities. Work status remained the same for post-operative patients which unemployment increased in the standard wait pre-operative cohort.

2.  External Technology Assessments

a. CMS did not request an external technology assessment (TA) on this issue.

b. There were no AHRQ reviews on this topic.

c. There are no Blue Cross/Blue Shield Health Technology Assessments written on this topic within the last three years.

d. There were two publications in the COCHRANE database, and both were tangentially related.

Both noted that there are gaps in the clinical evidence base for gender reassignment surgery.

Twenty Years of Public Health Research: Inclusion of Lesbian, Gay, Bisexual, and Transgender Populations Boehmer U. Am J Public Health . 2002; 92: 1125–30.

“Findings supported that LGBT issues have been neglected by public health research and that research unrelated to sexually transmitted diseases is lacking.”

A systematic review of lesbian, gay, bisexual and transgender health in the West Midlands region of the UK compared to published UK research . West Midlands Health Technology Assessment Collaboration. Health Technology Assessment Database. Meads, et al., 2009. No.3.

“Further research is needed but must use more sophisticated designs with comparison groups. This systematic review demonstrated that there are so many gaps in knowledge around LGBT health that a wide variety of studies are needed.”

e. There were no National Institute for Health and Care Excellence (NICE) reviews/guidance documents on this topic.

f. There was a technology assessment commissioned by the New Zealand Ministry of Health and conducted by New Zealand Health Technology Assessment (NZHTA) (Christchurch School of Medicine and the University of Otago).

Tech Brief Series: Transgender Re-assignment Surgery Day P . NZHTA Report . February 2002;1(1). http://nzhta.chmeds.ac.nz/publications/trans_gender.pdf

The research questions included the following: (1) Are there particular subgroups of people with transsexualism who have met eligibility criteria for gender reassignment surgery (GRS) where evidence of effectiveness of that surgery exists? And (2) If there is evidence of effectiveness, what subgroups would benefit from GRS?” Based upon the research, “Some 593 possibly relevant articles in abstract form were identified of which 70 articles were retrieved in full text.”

The NZHTA stated, “The reviewed studies may indicate that early, rather than delayed, sex reassignment surgery is of greater benefit to transsexual people who have gone through rigorous assessment procedures and have been accepted for surgery. Also, the reviewed studies identify characteristics of groups defined as core and non-core transsexual people, but these characteristics are heterogeneous and anecdotal.”

The NZHTA also stated, “Gender reassignment surgery may benefit some carefully assessed and selected transsexual people who have satisfied recognized diagnostic and eligibility criteria, and have received recognized standards of care for surgery. More research is required to improve the evidence base identifying the subgroups of transsexual people most likely to benefit from sex reassignment surgery.”

3.  Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) Meeting

CMS did not convene a MEDCAC meeting.

4.  Evidence-Based Guidelines

a. American College of Obstetricians and Gynecologists (ACOG)

Though ACOG did not have any evidence-based guidelines on this topic, they did have the following document:

Health Care for Transgender Individuals: Committee Opinion

Committee on Health Care for Underserved Women; The American College of Obstetricians and Gynecologists. Dec 2011, No. 512. Obstet Gyncol. 2011;118:1454-8.

“Questions [on patient visit records] should be framed in ways that do not make assumptions about gender identity, sexual orientation, or behavior. It is more appropriate for clinicians to ask their patients which terms they prefer. Language should be inclusive, allowing the patient to decide when and what to disclose. The adoption and posting of a nondiscrimination policy can also signal health care providers and patients alike that all persons will be treated with dignity and respect. Assurance of confidentiality can allow for a more open discussion, and confidentiality must be ensured if a patient is being referred to a different health care provider. Training staff to increase their knowledge and sensitivity toward transgender patients will also help facilitate a positive experience for the patient.”

b. American Psychiatric Association

Report of the American Psychiatric Association Task Force on Treatment of Gender Identity Disorder Byne, W, Bradley SJ, Coleman E, Eyler AE, Green R, Menvielle EJ, Meyer-Bahlburg HFL, Richard R. Pleak RR, Tompkins DA. Arch Sex Behav . 2012; 41:759–96.

The American Psychiatric Association (APA) was unable to identify any Randomized Controlled Trials (RTCs) regarding mental health issues for transgender individuals.

"There are some level B studies examining satisfaction/regret following sex reassignment (longitudinal follow-up after an intervention, without a control group); however, many of these studies obtained data retrospectively and without a control group (APA level G). Overall, the evidence suggests that sex reassignment is associated with an improved sense of well-being in the majority of cases, and also indicates correlates of satisfaction and regret. No studies have directly compared various levels of mental health screening prior to hormonal and surgical treatments on outcome variables; however, existing studies suggest that comprehensive mental health screening may be successful in identifying those individuals most likely to experience regrets."

Relevant Descriptions of APA Evidence Coding System/Levels:

[B] Clinical trial. A prospective study in which an intervention is made and the results of that intervention are tracked longitudinally. Does not meet standards for a randomized clinical trial.”

[G] Other. Opinion-like essays, case reports, and other reports not categorized above.”

c. Endocrine Society

Endocrine Treatment of Transsexual Persons: an Endocrine Society Clinical Practice Guideline.

Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, Gooren LJ, Meyer WJ 3rd, Spack NP, Tangpricha V, Montori VM; Endocrine Society. J Clin Endocrinol Metab . 2009;94:3132-54.

This guideline primarily addressed hormone management and surveillance for complications of that management. A small section addressed surgery and found the quality of evidence to be low.

“This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence, which was low or very low.”

d. World Professional Association for Transgender Health (WPATH)

Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People (Version 7) . Coleman E, Bockting W, Botzer M, Cohen-Kettenis P, DeCuypere G, Feldman J, Fraser L, Green J, Knudson G, Meyer WJ, Monstrey S, Adler RK, Brown GR, Devor AH, Ehrbar R, Ettner R, Eyler E, Garofalo R, Karasic DH, Lev AI, Mayer G, Meyer-Bahlburg H, Hall BP, Pfäfflin F, Rachlin K, Robinson B, Schechter LS, Tangpricha V, van Trotsenburg M, Vitale A, Winter S, Whittle S, Kevan R. Wylie KR, Zucker K. www.wpath.org/_files/140/files/Standards%20of%20Care,%20V7%20Full%20Book.pdf Int J Transgend. 2011;13:165–232.

The WPATH is “an international, multidisciplinary, professional association whose mission is to promote evidence-based care, education, research, advocacy, public policy, and respect in transsexual and transgender health.”

WPATH reported, “The standards of care are intended to be flexible in order to meet the diverse health care needs of transsexual, transgender, and gender-nonconforming people. While flexible, they offer standards for promoting optimal health care and guiding the treatment of people experiencing gender dysphoria—broadly defined as discomfort or distress that is caused by a discrepancy between a person’s gender identity and that person’s sex assigned at birth (and the associated gender role and/or primary and secondary sex characteristics) (Fisk, 1974; Knudson, De Cuypere, & Bockting, 2010b).”

The WPATH standards of care (SOC) “acknowledge the role of making informed choices and the value of harm-reduction approaches.”

The SOC noted, “For individuals seeking care for gender dysphoria, a variety of therapeutic options can be considered. The number and type of interventions applied and the order in which these take place may differ from person to person (e.g., Bockting, Knudson, & Goldberg, 2006; Bolin, 1994; Rachlin, 1999; Rachlin, Green, & Lombardi, 2008; Rachlin, Hansbury, & Pardo, 2010). Treatment options include the following:

• Changes in gender expression and role (which may involve living part time or full time in another gender role, consistent with one’s gender identity);
• Hormone therapy to feminize or masculinize the body;
• Surgery to change primary and/or secondary sex characteristics (e.g., breasts/chest, external and/or internal genitalia, facial features, body contouring);
• Psychotherapy (individual, couple, family, or group) for purposes such as exploring gender identity, role, and expression; addressing the negative impact of gender dysphoria and stigma on mental health; alleviating internalized transphobia; enhancing social and peer support; improving body image; or promoting resilience.”

The SOC were carefully reviewed because they are frequently cited as the basis of management by clinicians, including some of the clinical groups with whom CMS spoke used it as a flexible guide. In the WPATH’s SOC Appendix D titled “Evidence for Clinical Outcomes of Therapeutic Approaches,” WPATH noted, “One of the real supports for any new therapy is an outcome analysis. Because of the controversial nature of sex reassignment surgery, this type of analysis has been very important. Almost all of the outcome studies in this area have been retrospective.” They further reported, “More studies are needed that focus on the outcomes of current assessment and treatment approaches for gender dysphoria.”

e. American Psychological Association

Suggested citation until formally published in the American Psychologist : American Psychological Association. (2015): Guidelines for Psychological Practice with Transgender and Gender Nonconforming People Adopted by the Council of Representatives, August 5 & 7, 2015. www.apa.org/practice/guidelines/transgender.pdf

“The purpose of the Guidelines for Psychological Practice with Transgender and Gender Nonconforming People (hereafter Guidelines) is to assist psychologists in the provision of culturally competent, developmentally appropriate, and trans‐affirmative psychological practice with TGNC people.”

“These Guidelines refer to psychological practice (e.g., clinical work, consultation, education, research, training) rather than treatment.”

5.  Other Reviews

a. Institute of Medicine (IOM)

The Health of Lesbian, Gay, Bisexual, and Transgender People: Building a Foundation for Better Understanding. Robert Graham (Chair); Committee on Lesbian, Gay, Bisexual, and Transgender Health Issues and Research Gaps and Opportunities. (Study Sponsor: The National Institutes of Health). Issued March 31, 2011. http://www.nationalacademies.org/hmd/Reports/2011/The-Health-of-Lesbian-Gay-Bisexual-and-Transgender-People.aspx

“To advance understanding of the health needs of all LGBT individuals, researchers need more data about the demographics of these populations, improved methods for collecting and analyzing data, and an increased participation of sexual and gender minorities in research. Building a more solid evidence base for LGBT health concerns will not only benefit LGBT individuals, but also add to the repository of health information we have that pertains to all people.”

“Best practices for research on the health status of LGBT populations include scientific rigor and respectful involvement of individuals who represent the target population. Scientific rigor includes incorporating and monitoring culturally competent study designs, such as the use of appropriate measures to identify participants and implementation processes adapted to the unique characteristics of the target population. Respectful involvement refers to the involvement of LGBT individuals and those who represent the larger LGBT community in the research process, from design through data collection to dissemination.”

b. National Institutes of Health (NIH)

National Institutes of Health Lesbian, Gay, Bisexual, and Transgender (LGBT) Research Coordinating Committee. Consideration of the Institute of Medicine (IOM) report on the health of lesbian, gay, bisexual, and transgender (LGBT) individuals . Bethesda, MD: National Institutes of Health; 2013. http://report.nih.gov/UploadDocs/LGBT%20Health%20Report_FINAL_2013-01-03-508%20compliant.pdf

In response to the IOM report, the NIH LBGT research Coordinating Committee noted that most of the health research for this set of populations is “ focused in the areas of Behavioral and Social Sciences, HIV (human immunodeficiency virus)/AIDS, Mental Health, and Substance Abuse. Relatively little research has been done in several key health areas for LGBT populations including the impact of smoking on health, depression, suicide, cancer, aging, obesity, and alcoholism.”

6.  Pending Clinical Trials

ClinicalTrials.gov There is one currently listed and recently active trial directed at assessment of the clinical outcomes pertaining to individuals who have had gender reassignment surgery. The study appears to be a continuation of work conducted by investigators cited in the internal technology assessment.

NCT01072825 (Ghent, Belgium sponsor) European Network for the Investigation of Gender Incongruence (ENIGI) is assessing the physical and psychological effects of the hormonal treatment of transgender subjects in two years prior to reassignment surgery and subsequent to surgery. This observational cohort study started in 2010 and is still in progress.

7.  Consultation with Outside Experts

Consistent with the authority at 1862(l)(4) of the Act, CMS consulted with outside experts on the topic of treatment for gender dysphoria and gender reassignment surgery.

Given that the majority of the clinical research was conducted outside of the United States, and some studies took place in a or suggested continuity-of-care and coordination-of-care were beneficial to health outcomes, we conducted expert interviews with centers across the U.S. that provided some form of specialty-focused or coordinated care for transgender patients. These interviews informed our knowledge about the current healthcare options for transgender people, the qualifications of the professionals involved, and the uniqueness of treatment options. We are very grateful to the organizations that made time to discuss treatment for gender dysphoria with us.

From our discussions with the all of the experts we spoke with, we noted the following practices in some centers: (1) specialized training for all staff about transgender healthcare and transgender cultural issues; (2) use of an intake assessment by either a social worker or health care provider that addressed physical health, mental health, and other life factors such as housing, relationship, and employment status; (3) offering primary care services for transgender people in addition to services related to gender-affirming therapy/treatments; (4) navigators who connected patients with name-change information or other legal needs related to gender; (5) counseling for individuals, groups, and families; (6) an informed-consent model whereby individuals were often referred to as “clients” instead of “patients,” and (7) an awareness of depression among transgender people (often measured with tools such as the Adult Outcomes Questionnaire and the Patient Health Questionnaire (8) and how, in some instances, with hormone treatment for gender dysphoria, the depression lessens.

8.  Public Comments

Initial Comment Period: 12/03/2015 – 01/02/2016

During the initial comment period, we received 103 comments. Of those, 78% supported coverage of gender reassignment surgery, 15% opposed, and 7% were neutral. The majority of comments supporting coverage were from individuals and advocacy groups. All of the initial public comments are available at: https://www.cms.gov/medicare-coverage-database/details/nca-view-public-comments.aspx?NCAId=282&ExpandComments=n&bc=ACAAAAAAAgAAAA%3d%3d&

VIII. CMS Analysis

National coverage determinations are determinations by the Secretary with respect to whether or not a particular item or service is covered nationally under § 1862(l)(6) of the Act. In general, in order to be covered by Medicare, an item or service must fall within one or more benefit categories contained within Part A or Part B and must not be otherwise excluded from coverage. Moreover, in most circumstances, the item or service must be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member (§1862(a)(1)(A)). The Supreme Court has recognized that “[t]he Secretary’s decision as to whether a particular medical service is ‘reasonable and necessary’ and the means by which she implements her decision, whether by promulgating a generally applicable rule or by allowing individual adjudication, are clearly discretionary decisions.” Heckler v. Ringer, 466 U.S. 602, 617 (1984). See also, 78 Fed. Reg. 48,164, 48,165 (August 7, 2013)

When making national coverage determinations, we consider whether the evidence is relevant to the Medicare beneficiary population. In considering the generalizability of the results of the body of evidence to the Medicare population, we carefully consider the demographic characteristics and comorbidities of study participants as well as the provider training and experience. This section of the proposed decision provides an analysis of the evidence, which included the published medical literature and guidelines pertaining to gender dysphoria, that we considered during our review to answer the question:

A. Analysis

1. Study Demographics

These studies were conducted in a total of 13 countries. Most were conducted in Europe (a total of 24 in Europe: Belgium four, Germany four, Holland two, Norway one, Spain two, Sweden four, Switzerland three, the United Kingdom three [not including the Barrett, 1998 study and the duplicative Megeri, Khoosal, 2007 study], and Yugoslavia one). One was in Asia (Singapore); one in South America (Brazil). Seven were conducted in North America (U.S. six, Canada one). One of the North American studies was a U.S.-conducted internet survey with non-U.S. and U.S. participants with a sub-analysis of the U.S. patients (Newfield et al., 2006).

All of the studies, with the exception of a national-wide mortality study (Dhejne et al., 2011), the international internet survey (Newfield et al., 2006), and the internet/convention site survey (Ainsworth, Spiegel, 2010), were conducted with patient populations from single sites. Many of these clinical centers cited in these studies were specialized tertiary referral centers offering comprehensive, integrated (psychiatric-psychological, endocrine, and surgical) care and whose staff could have been involved in both the patient care and the study. Of the studies reviewed, the Lawrence, 2006 study was conducted by a physician psychologist who surveyed the patient population of a single U.S. surgeon. The Ainsworth, Spiegel, 2010 study was conducted by a U.S. otolaryngologist with extensive surgery training who assessed the impact of facial feminization on transgender patients. The Hess et al. 2014 study was undertaken at a German university urologic specialty clinic. The Wolfradt, Neumann, 2001 study was conducted in Germany by a university otorhinolaryngologist and psychologist on patients who had undergone vocal cord surgery after reassignment surgery. The Ruppin, Pfafflin 2015 study was undertaken by investigators who had seen the patients in a German forensic psychotherapy clinic.

2. Patient Population

Demographic assessments of the studies revealed that the mean ages of participants were in the 20s and 30s. (See Appendix C and Appendix D). Even when including standard deviation, most patients included in the study were under the age 60. Age of participants in the reviewed studies is important to assess generalizability to the Medicare population which is comprised predominantly of adults’ age 65 years and older. While certain younger disabled adults are included in Medicare, generalizability of studies performed outside in the U.S. is likely reduced further since criteria to determine disability is unique to Medicare. When reporting ages of patients participating in studies, studies included mean age of population, but often failed to reveal standard deviation of the population. Most studies reported pre and post gender reassignment surgery ages, though some studies only reported post-surgery ages (Dehjne, 2011; Kuhn et al., 2009; Rakic et al., 1996; Ruppin, Pfafflin, 2015; Udeze et al., 2008; Megeri, Khoosal, 2007; Wolfradt, Neumann, 2001; Blanchard et al., 1985; Weyers et al., 2009; Wierckx et al., 2011; Eldh et al., 1997; Hess et al., 2014; Lawrence, 2006; Salvador et al., 2012; Tsoi, 1993).

There was extensive lack of study participation and loss to follow-up in the published studies. (See Appendix C and Appendix G). This suggests that the population that seeks evaluation/treatment for gender dysphoria and/or applies for reassignment surgery is not the same population that undergoes reassignment surgery without hesitation or regret. The notable numbers of incomplete questionnaires similarly raises questions. This selection bias limits generalizability of any results.

3. Study Design

As noted earlier, a number of research designs were found when exploring the question, “Does gender reassignment surgery improve health outcomes for Medicare beneficiaries with gender dysphoria?” (See Appendix C). The vast majority of studies found were observational in nature though there was a single randomized trial (Mate-Kole et al., 1990) (see Figure 1). Two of the studies were blinded. (Hess, 2014; Lawrence, 2006) A total of 29 studies were not blinded. The blinding status of the two internet surveys is unknown (Ainsworth, Spiegel, 2010; Newfield et al., 2006).

Observational studies can be prospective, retrospective, or have components of both. But each observational study design has limitations, and may not be able to show the true association between gender/reassignment surgery and improved health outcomes. Limitations of observational studies include that they frequently generate unreliable findings, and they also generate bias; because of confounding, causal inferences cannot reliably be drawn. Thus these types of studies are limited in terms of evidentiary weight. Only a true experimental study (e.g., randomized clinical trial) has the potential to demonstrate a causal relationship between two factors.

In general, one of the advantages of prospective studies is that they could potentially help determine factors associated with improved outcomes due to their longitudinal observation over time, and the collection of results at regular time intervals minimizes recall error. However, retrospective studies have problems including: some key statistics cannot be measured, significant biases including selection bias, recall bias, and information bias may limit a retrospective study’s applicability. Another problem with retrospective studies is that the temporal relationship between variables is frequently difficult to assess. Finally, it is difficult to control exposure or outcome assessment in a retrospective study design.

Studies that use controls as part of its research design have higher evidentiary weight than studies that lack controls. That is because the use of controls can help to eliminate the possibility of confounding. But controls by themselves are no guarantee of complete validity. In terms of the use of controls in these studies that we evaluated some studies had no concurrent controls; some studies used control groups, but they were not concurrent; some studies used semi-matched controls; and in other studies patients served as their own controls.

Seventeen observational studies, of which 10 used longitudinal and 7 used cross-sectional study designs, had formal control groups. In this group of studies, the cross-sectional studies used various controls including healthy volunteers and patients with other disorders or treatments. In this same group of studies, the longitudinal studies used various controls including the patients as their own serial control, other treatment groups in addition to having patients serve as their own controls, and control cohorts derived from national databases. Among the longitudinal studies with used patients as their own controls, 4 used self-report test instruments that were validated in large populations. Of these 4, 1 had more than 100 subjects, self-reported and others, or other cohorts using either national data or national registries. Some observational studies included in this analysis had surgery-only populations and used no controls, or used indirect controls incorporating normative testing. The remainder of the observational studies had mixed populations that included surgical patients and patients using other treatments or patients treated with non-genital gender reassignment surgical procedures. The studies that included groups with mixed populations either had no controls, or used indirect controls (statistical methods included ANOVA, correlation, or regression).

Our review included 25 prospective studies. Of these prospective studies, two used a retrospective approach to acquire data for a single parameter (Eldh et al., 1997; Johansson et al., 2009); one prospective study used a retrospective approach to acquire data for several parameters (Ruppin, Pfafflin, 2015); and one study used a prospective approach beginning in 2003, but used a retrospective approach for data accumulated prior to that year (Leinung et al., 2013).

We found three retrospective studies (Asscheman et al., 2011; Dhejne et al., 2011; Landen et al., 1998). One study had at least a partially retrospective component, but with insufficient information to determine whether any of the data were obtained prospectively (Haraldsen, Dahl, 2000).

There were 11 longitudinal studies (Asscheman et al., 2011; Dhejne et al., 2011; Heylens et al., 2014; Kockott, Fahrner, 1987; Landen et al., 1998; Mate-Kole et al., 1979; Rakic et al., 1996; Ruppin, Pfafflin, 2015; Smith et al., 2005; Udeze et al,, 2008). Ten of the longitudinal studies occurred in the group of studies with a designated control group (all of the above with the exception of Asscheman et al., 2011). In seven of the 11 longitudinal studies, the patients served as their own control over time before and after surgery (Heylens et al., 2014; Kockott, Fahrner, 1987; Meyer, Reter, 1979; Rakic et al., 1996; Ruppin, Pfafflin, 2015; Smith et al., 2005; Udeze et al., 2008).

There were 19 cross-sectional studies (Ainworth, 2010; Haraldsen, Dahl, 2000; Beatrice, 1985; Kraemer et al., 2008; Kuhn et al., 2009; Mate-Kole et al., 1988; Wolfradt, Neumann, 2001; Blanchard et al., 1985; Weyers et al., 2009; Wierckx et al., 2011; Eldh et al., 1997; Hess et al., 2014; Lawrence, 2006; Salvador et al., 2012; Tsoi, 1993; Gómez-Gil et al., 2012, Hepp et al., 2005; Motmans et al., 2012; Newfield et al., 2006; Gómez-Gil et al., 2013; Johansson et al., 2009; Leinung et al., 2013). Of this number, two were cross-sectional with the exception of data collection for aspects of a single parameter that had occurred in the past (Eldh et al., 1997; Johansson et al., 2009), and one study asked participants to recall the status of a parameter prior to treatment (Wierckx et al., 2011a).

Seventeen of the studies had explicit control groups. Of the studies with explicit control groups, two studies derived controls from national databases (Dhejne et al., 2011 and 2014; Landen et al., 1998); five studies used the patients themselves as longitudinal controls (Heylens 2014a; Rakic et al. 1996; Ruppin, Pfafflin, 2015; Smith et al., 2005a; Udeze et al., 2008; Megeri 2007); eight used various other controls (Ainsworth, Spiegel, 2010; Beatrice 1985; Haraldsen, Dahl, 2000; Kraemer et al., 2008; Kuhn et al., 2009; Mate-Kole et al., 1988 and 1990; Wolfradt, Neumann, 2001); and two studies used both treatment-type cohorts and patients themselves as controls (Kockott, Fahrner, 1987; Meyer, Reter 1979).

A number of studies consisted of surgical series, but in these studies there were no concurrent controls (Wierckx et al., 2011; Salvador et al., 2012; Blanchard et al., 1985; Tsoi, 1993; Eldh et al., 1997; Hess et al., 2014; Lawrence, 2006; Weyers, 2009a). In three surgical series normative data from psychometric instruments were used as the control (Blanchard et al., 1985a; Weyers 2009a; Wierckx et al., 2011b). In five surgical series, controls were lacking (except for the use of serial employment data in the Eldh et al. 1997 study) (Eldh et al., 1997; Hess 2014; Lawrence 2006; Salvador 2012; Tsoi, 1993).

Patients underwent a variety of surgical interventions in five studies. There were no controls. The role of surgical intervention was assessed indirectly post hoc by statistical techniques (analysis of variance and regression) (Gomez-Gil et al., 2012 and 2014; Hepp et al., 2005; Motmans et al., 2011; Newfield et al., 2006).

As mentioned in previous paragraphs, some prospective studies included in this analysis were cross-sectional in nature, and consisted of treated cohorts using a normative test, or a treatment cohort along with volunteer healthy cohorts. However, as we have noted, cross-sectional studies also have their limitations, including inability to determine temporal relationship between exposure and outcome (lacks time element). In other words, findings noted in a cross-sectional design cannot be inferred, because only current health and exposure to interventions are being studied. Also measurement error is an issue. Longitudinal studies with controls are most appropriate for determining this relationship between exposure and outcomes.

Observational studies have limitations. The lack of blinding has the potential to interfere with patient reported outcomes, which by their nature are subjective. Observational studies are prone to selection bias. Patients who seek treatment may not be the same as those who complete treatment-particularly if there are serial steps in the treatment process. (See Appendix G) Cross-sectional studies are prone to confounding. The impact of a particular step in a multi-faceted treatment process cannot be ascertained. The lack of a control group does not permit attribution of any outcome change to a specific intervention. There were seven studies where the patients themselves serve as longitudinal controls. The lack of a control makes it difficult to assess the results because there is not another group to make comparisons.

4. Psychometric Measurement Tools

There is also myriad use of measurement tools to assess patients suffering with gender dysphoria. (See Appendix E for a list of Psychometric Measurement tools.)

Some of the domains addressed in psychometric measurement tools measure the degree of depression and anxiety, body imagery, quality of life, identity traits, general wellbeing, physical and psychological function, self-concept, and others. Some of these measurement tools have been validated for patients with this condition, while others have been validated for other medical conditions. Some of the measurement tools found in this assessment were self-developed and there is no mention of validity when trying to determine if the test reliably measures what it is intended to measure.

5. Study Endpoints

A wide variety of study endpoints were used. Endpoints were collected from a number of sources, including self-reporting, clinician assessment, and medical records as well national databases. Some of the endpoints included patient reported quality of life (QOL) as manifest by psychometric testing, sense of well-being, body imagery, anxiety and depression, sexual function and satisfaction, and social function. Objective endpoints included employment status, psychiatric function, and morbidity and mortality as well as adverse events.

Thirty of the studies employed 31 psychometric tools or investigator designed self-report surveys. (See Appendix E) Twenty investigators designed their own measurement tools or modified those of others.

External information on test validity, the size/composition of the reference population(s), diagnostic cut-points, and scoring was often not available because it was unpublished, proprietary, or in a non-English language. Six of the instruments, all non-specific, (the European QOL Survey, MMPI, SF-36, SCL-90, TSCS, and WHO-QOL-BREF), appear to have substantive normative data for comparative scoring (i.e., reference populations (≥1000) and obtained through representative sampling). Although these tools had been validated in a reference population, none had been validated in populations with gender dysphoria. Furthermore the investigators did not provide diagnostic cut-points and did not pre-specify the magnitude of test score change or test score difference considered to be biologically significant so the clinical importance could not be easily ascertained.

Only four investigator groups used only these psychometric tools validated in other large populations as their test instrument (Beatrice, 1985; Haraldsen, Dahl, 2000; Motmans et al., 2012; Newfield et al., 2006). Nine investigator groups used a mix of psychometric tools validated in large normative populations, less well validated tools, and/or self-designed tools (Ainsworth, Spiegel, 2010; Blanchard et al., 1985a; Gomez-Gil et al., 2014; Heylens 2014a; Ruppin, Pfafflin, 2015; Smith et al., 2005a (Udeze et al., 2008; Megeri 2007; Weyers 2009a; Wierckx et al., 2011b). Nine investigators used self-designed tools as their only test instrument (Eldh et al., 1997; Hess 2014; Johansson et al, 2009; Kockott, Fahrner, 1987; Lawrence, 2006; Meyer, Reter 1979; Rakic 1996; Salvador 2012; Tsoi 1993). A single investigator did not use any type of testing tool and provided only descriptive statistics (Leinung et al., 2013).

Three studies reported on complications linked or possibly linked to hormone treatment (Asscheman et al., 2011; Dhejne et al., 2011; Leinung et al., 2013), six studies reported on complications from reassignment surgery (Eldh et al., 1997; Lawrence, 2006; Ruppin, Pfafflin, 2015; Smith et al., 2005; Weyers et al., 2009; Wierckx et al., 2011). One study reported on serious and formalized regret for undergoing reassignment surgery (Landen et al., 1998), and one study reported on a patient with suicidal ideation who requested phallus removal (Meyer, Reter, 1979). Others reported on less severe or less formalized levels of regret. Five studies reported on the treatment or diagnosis of psychiatric disease (Dhejne et al., 2011; Haraldsen, Dahl, 2000; Hepp et al., 2005; Landen et al., 1998; Leinung et al., 2013; Meyer, Reter, 1979; Ruppin, Pfafflin, 2015; Udeze et al., 2008). Two studies reported on the history of psychiatric disease in their patient populations (Matte-Kole, 1988; Matte Kole, 1990).

Four studies reported on suicide attempts (Dehjne et al., 2011; Eldh et al., 1997; Heylens et al., 2013; Kockott, Fahrner, 1987), two studies reported on the history of suicide attempts in their patient population (Matte-Kole, 1988; Matte Kole, 1990). Three studies reported on suicide, of which one of them occurred incidentally (Asscheman et al., 2011; Blanchard et al., 1985; Dhejne et al., 2011). Two studies also reported on mortality (Asscheman et al., 2011; Dhejne et al., 2011).

There was a great degree of inconsistency in endpoints. Also endpoints were collected from a number of sources, including self-reporting, clinician assessment, and medical records as well national databases. Endpoints lacked operational definitions thus making their applicability difficult. CMS is interested in knowing what patients diagnosed with gender dysphoria believe are important endpoints that should be studied.

Mortality and Regret as Endpoints

Certain kinds of objective outcomes can be assessed by other types of study designs-albeit somewhat less robust. These include mortality and regret (as manifest by request for surgical reversal) when the data are rigorously prospectively collected in a comprehensive registry for all patients who have met specified entry criteria and treatment criteria.

More specifically, Swedish investigators extracted data from registries at the National Board of Health and Welfare to which all patients seeking reassignment surgery or reversal of reassignment surgery must make formal application. In the initial 1998 study, of the 233 applicants for reassignment surgery between July 1972 and June 1992, 20 were denied surgery, and subsequently 13 (3.8%) surgical patients requested return to the natal sex (Landen et al., 1998). In the 2014 follow-up study, of the 767 applicants for reassignment surgery or a change in legal status after surgery between 1960-2010, 86 were denied, and subsequently 15 (2.2%) requested reversal to the natal gender (Dhejne et al., 2014). Although the data from the two studies are not directly comparable because of the much shorter follow-up period in the latter study and although the analyses also did not consider other possible expressions of regret including suicide, the studies suggest that the majority of highly vetted patients in a structured care system do not express regret as defined by a formal request for return to natal gender status (Dhejne et al., 2011). The study, however, cannot assess the impact of gender reassignment surgery per se because of the confounding introduced by the other interventions.

Swedish investigators also conducted the most comprehensive study with functional endpoints of the 33 studies reviewed. This study relied on compulsory national databases (Dhejne et al., 2011) tracked all patients who had undergone reassignment surgery (at a mean age 35.1 years) over a 30 year interval and compared them to 6480 matched controls from the general population. They identified both increased mortality and increased psychiatric hospitalization. The mortality was primarily due to completed suicides (19.1-fold greater), but death due to neoplasm and cardiovascular disease was increased 2 to 2.5 times as well. The divergence in mortality from the Swedish population did not become apparent until after 10 years. The risk for psychiatric hospitalization was 2.8 times greater than in control Swedes even after adjustment for prior psychiatric disease (18%). The risk for attempted suicide was greater in male-to-female patients regardless of the sex of the control. For the same reasons as delineated above, this study cannot assess the impact of gender reassignment surgery per se because of the confounding introduced by the other interventions. The finding of this study demonstrated that reassignment surgery does not return patients to a normal level of morbidity risk and that the morbidity risk is significant even in highly vetted patients in a structured care system.

B. Discussion

The question addressed in this NCD is whether there is sufficient evidence to conclude that gender reassignment surgery improves health outcomes for Medicare beneficiaries with gender dysphoria.

Gender dysphoria by the latest and prior nomenclature is a state in which there is incongruence between the gender assigned at birth and the gender(s) with which the person identifies. This incongruence may result in varying degrees of discontent and distress. Satisfaction and quality-of-life are well recognized as “latent variables” (hypothetical constructs) which cannot be measured directly (Borsboom et al., 2003; Newsom, 2015). As such, observable entities are used to infer or approximate satisfaction and/or quality-of-life. It may be challenging to identify parameters that truly reflect the nature and the magnitude of dysphoria in the individual. This challenge is followed by the need to know to what extent a specific test measures that which it purports to measure (test validity) and whether repeat testing will yield a comparable answer (test reliability).

The investigators of the clinical research reviewed in this NCD have attempted to measure dysphoria levels by objective data elements and by use of various psychometric and function scales/surveys. The objective data elements include a number of variables such as employment, morbidity, and formal requests for surgical reversal.

The psychometric tools used to assess outcomes have limitations. Many of the instruments that are most specific for the condition were designed by the investigators themselves or by other investigators in the field. In addition, the relevant diagnostic cut-points for scores and changes in scores that are clinically significant should be delineated to permit adequate interpretation of test results. As such, these studies were not definitive in nature.

Other factors might impact the utility of a given test. Patients undergo serial evaluations and a sequence of treatments (Bockting et al., 2011). These other interventions may reduce internal validity of the test. The affirmation and support obtained in psychotherapy-psychiatric care, the adjustment confidence gained in real life cross-gender behavior, and/or the physical and mental changes from hormone therapy may be (an) alternative cause(s) of the findings. Several studies suggest that there is a major therapeutic benefit from hormone therapy (Colizzi et al., 2013; Gómez-Gil et al., 2011; Gorin-Lazard et al., 2011, 2013; Heylens et al., 2014; Dubois, 2012). Another suggests that there is therapeutic benefit from time in the preferred gender role without other intervention (Greenberg, Laurence, 1981). As such, results from cross-sectional studies may be misleading. None of the studies used adequately matched controls over time. We believe longitudinal studies with serial assessment of the same patients would provide more robust answers. We note that even from the results from the four studies in which patients served as their own controls and which used an instrument known to be validated in large populations were negative (i.e., there was no improvement in psychometric or quality of life outcomes when patients were tested just prior to and at some point after the reassignment surgical intervention). (Heylens, 2014; Ruppin, Pfafflin, 2015; Smith et al., 2005; Udeze et al., 2008). Further, rigorous studies with the use of appropriate comparison patients could better clarify the specific benefits and harms of each of the interventions.

CMS reviewed and considered potential objective measures of function including mortality, psychiatric treatment, and attempted suicide. None of the longitudinal studies in which patients served as their own control, however, comprehensively tracked changes in these events as objective measures of function before and after surgery. Events such as suicide and institutionalization were mentioned incidentally when describing patients excluded from a follow-up study or during the study (Heylens et al., 2014; Ruppin, Pfafflin, 2015). Other times investigators tracked these functional outcomes (e.g., psychiatric out-patient treatment, psychiatric in-patient treatment, and substance abuse) for the most current prior year (Ruppin, Pfafflin, 2015).

The most comprehensive study with functional endpoints, the Swedish study that followed all patients who had undergone reassignment surgery (at mean age 35.1 years) over a 30 year interval and compared them to 6480 matched controls, identified increased mortality and increased psychiatric hospitalization (Dhejne et al., 2011). The mortality was primarily due to completed suicides (19.1-fold greater than in control Swedes), but death due to neoplasm and cardiovascular disease was increased 2 to 2.5 times as well. The divergence in mortality from the Swedish population did not become apparent until after 10 years. The risk for psychiatric hospitalization was 2.8 times greater than in controls even after adjustment for prior psychiatric disease (18%). The risk for attempted suicide was greater in male-to-female patients regardless of the gender of the control. Unfortunately, the study was not constructed to assess the impact of gender reassignment per se . The finding of this study, again, demonstrated that reassignment surgery does not return patients to a normal level of morbidity risk and that the morbidity risk is significant, because of its clinical importance, its persistence over the interval of data collection and the increase in risk over time for the individual.

1. Patient Care

Additional questions regarding the care of patients with gender dysphoria remain. The specific type(s) of gender/sex reassignment surgery (genital, non-genital) that could improve health outcomes in adults remain(s) uncertain because most studies included patients who had undertaken one or more of a spectrum of surgical procedures or did not define the specific surgical procedures under study. Furthermore, most studies did not assess specific surgical procedures except for technical aspects. Surgical techniques have changed significantly over the last 60 years (Bjerrome Ahlin et al., 2014; Doornaert, 2011; Green, 1998; Pauly, 1968; Selvaggi et al., 2007; Selvaggi, Bellringer, 2011; Tugnet et al., 2007; Doornaert, 2011).

The WPATH care recommendations presented a general framework and guidance on the care of transgender individual. The standards of care are often cited by entities that perform gender reassignment surgery. WPATH noted: “More studies are needed that focus on the outcomes of current assessment and treatment approaches for gender dysphoria.” Appendix D in the WPATH Standards of Care acknowledged the historical problems with evidentiary standards, the preponderance of retrospective data, and the confounding impact of multiple interventions, specifically distinguishing the impact of hormone therapy from surgical intervention.

The surgical expertise and care setting(s) required to improve health outcomes in adults with gender dysphoria remain(s) uncertain. The selection of a particular surgeon could become an important variable if subjective outcomes depend on functional surgical results (Ross 1989). Many of these procedures involve complicated gynecologic, urologic surgical techniques accompanied by significant risk (Goddard et al., 2007a; Kuhn et al., 2011; Lawrence, 2003; Leclere et al., 2015; Rachlin, 1999; Ruppin, Pfafflin, 2015). Most of the studies for reassignment surgery have been conducted in northern Europe at select centers with integrated care (psychological, psychiatric, endocrinologic, and surgical) in which there is sequential evaluation of patients for progressively more invasive interventions.

Additionally, CMS met with several stakeholders and conducted several interviews with centers that focus on healthcare for transgender individuals in the U.S. Primary care was often the centers’ main focus rather than gender reassignment surgery. Few of the U.S.-based reassignment surgeons we could identify work as part of an integrated practice, and few provide the most complex procedures.

2. Generalizability

With the variability in the study participants, providers and settings, the generalizability of the studies reviewed to the Medicare population is unclear. Many of the studies are old since they were conducted more than 10 years ago. Many of the programs were single-site centers without replication elsewhere. Most of these studies were conducted outside of the U.S. with far different medical systems for treatment and follow-up. The study populations were young and without significant physical or psychiatric co-morbidity. As noted above psychiatric co-morbidity may portend poor outcomes (Asscheman et al., 2011; Landen et al., 1998).

For the above reasons, it is difficult to generalize these studies to the Medicare population.

3. Knowledge Gaps

This patient population faces complex and unique challenges. The medical science in this area is evolving. There are, however, many gaps in the evidentiary base. These gaps have been delineated because they represent areas in which patient care can be optimized and which are opportunities for much needed research.

The Institute of Medicine, the National Institutes of Health, and others have delineated many of the gaps in the data. (Boehmer, 2002; HHS-HP, 2011; IOM, 2011; Kreukels-ENIGI, 2012; Lancet, 2011; Murad et al., 2010; NIH-LGBT, 2013) The current or completed studies listed in ClinicalTrials.gov are not structured to assess these gaps.

The currently available evidence has limitations:

• There were design deficiencies. All but one of the studies were observational in nature. All but two were non-blinded. The accompanying loss to follow-up suggests that there is selection bias and that the population that seeks treatment for gender dysphoria is not the same population that undergoes reassignment surgery without hesitation or regret.
• The psychometric and psychosocial function endpoints are not well validated.
• There were limitations of the psychosocial endpoints and of the data collection of other hard functional outcomes. Evidence on mortality and especially suicide was stronger. The mortality and psychiatric hospitalization rates even after vetting in highly structured programs are of concern.
• There are insufficient data to select optimal candidates for surgery.
• The results were inconsistent, but negative in the best studies, i.e., those that reduced confounding by testing patients prior to and after surgery and which used psychometric tests with some established validation in other large populations. (Atkins et al., 2004; Balshem et al., 2011; Chan, Altman, 2005; Deeks et al., 2003; Guyatt et al., 2008a-c; 2011a-e; Kunz, Oxman,1998; Kunz et al., 2007 and 2011; Odgaard-Jensen et al., 2011).
• Data on reassignment surgery performed on geriatric patients or follow-up data in geriatric patients who had reassignment surgery in the distant past is anecdotal (Orel, 2014).

C. Health Disparities

Four studies included information on racial or ethnic background. The participants in the 3 U.S. based studies were predominantly Caucasian (Beatrice, 1985; Meyer, Reter, 1979; Newfield et al., 2006). All of the participants in the single Asian study were Chinese (Tsoi, 1993). Additional research is needed in this area.

Based on a thorough review of the clinical evidence available at this time, there is not enough evidence to determine whether gender reassignment surgery improves health outcomes for Medicare beneficiaries with gender dysphoria. There were conflicting (inconsistent) study results – of the best designed studies, some reported benefits while others reported harms. The quality and strength of evidence were low due to the mostly observational study designs with no comparison groups, potential confounding and small sample sizes. Many studies that reported positive outcomes were exploratory type studies (case-series and case-control) with no confirmatory follow-up. Due in part to the generally younger and healthier study participants, the generalizability of the studies to the Medicare population is also unclear. Additional research is needed. This proposed conclusion is consistent with the West Midlands Health Technology Assessment Collaboration (2009) that reported “[f]urther research is needed but must use more sophisticated designs with comparison groups.” WPATH also noted the need for further research: “More studies are needed that focus on the outcomes of current assessment and treatment approaches for gender dysphoria.” Further, as mentioned earlier, patient preference is an important aspect of any treatment. With that in mind, CMS is interested in knowing from the patients with gender dysphoria what is important to them as a result of a successful gender reassignment surgery.

Knowledge on gender reassignment surgery for individuals with gender dysphoria is evolving. The specific role for various surgical procedures is less well understood than the role of hormonal intervention. Much of the available research has been conducted in highly vetted patients at select care programs integrating psychotherapy, endocrinology, and various surgical disciplines and operating under European medical management and regulatory structures. Standard psychometric tools need to be developed and tested in the patients with gender dysphoria to validly assess long term outcomes. As such, further evidence in this area would contribute to the question of whether gender reassignment surgery improves health outcomes in adults with gender dysphoria.

Because CMS is mindful of the unique and complex needs of this patient population and because CMS seeks sound data to guide proper care of the Medicare subset of this patient population, CMS strongly encourages robust clinical studies with adequate patient protections that will fill the evidence gaps delineated in this decision memorandum. As the Institute of Medicine (IOM, 2011) importantly noted: “Best practices for research on the health status of LGBT populations include scientific rigor and respectful involvement of individuals who represent the target population. Scientific rigor includes incorporating and monitoring culturally competent study designs, such as the use of appropriate measures to identify participants and implementation processes adapted to the unique characteristics of the target population. Respectful involvement refers to the involvement of LGBT individuals and those who represent the larger LGBT community in the research process, from design through data collection to dissemination.”

IX. Proposed Decision

X. appendices.

A. Appendix A

Diagnostic & Statistical Manual of Mental Disorders (DSM) Criteria for Disorders of Gender Identity since 1980

B. Appendix B

1. General Methodological Principles of Study Design

When making national coverage determinations, CMS evaluates relevant clinical evidence to determine whether or not the evidence is of sufficient quality to support a finding that an item or service is reasonable and necessary. The overall objective for the critical appraisal of the evidence is to determine to what degree we are confident that: 1) the specific assessment questions can be answered conclusively; and 2) the intervention will improve health outcomes for patients.

We divide the assessment of clinical evidence into three stages: 1) the quality of the individual studies; 2) the generalizability of findings from individual studies to the Medicare population; and 3) overarching conclusions that can be drawn from the body of the evidence on the direction and magnitude of the intervention’s potential risks and benefits.

The methodological principles described below represent a broad discussion of the issues we consider when reviewing clinical evidence. However, it should be noted that each coverage determination has its unique methodological aspects.

Assessing Individual Studies

Methodologists have developed criteria to determine weaknesses and strengths of clinical research. Strength of evidence generally refers to: 1) the scientific validity underlying study findings regarding causal relationships between health care interventions and health outcomes; and 2) the reduction of bias. In general, some of the methodological attributes associated with stronger evidence include those listed below:

• Use of randomization (allocation of patients to either intervention or control group) in order to minimize bias.
• Use of contemporaneous control groups (rather than historical controls) in order to ensure comparability between the intervention and control groups.
• Prospective (rather than retrospective) studies to ensure a more thorough and systematical assessment of factors related to outcomes.
• Larger sample sizes in studies to demonstrate both statistically significant as well as clinically significant outcomes that can be extrapolated to the Medicare population. Sample size should be large enough to make chance an unlikely explanation for what was found.
• Masking (blinding) to ensure patients and investigators do not know to which group patients were assigned (intervention or control). This is important especially in subjective outcomes, such as pain or quality of life, where enthusiasm and psychological factors may lead to an improved perceived outcome by either the patient or assessor.

Regardless of whether the design of a study is a randomized controlled trial, a non-randomized controlled trial, a cohort study or a case-control study, the primary criterion for methodological strength or quality is the extent to which differences between intervention and control groups can be attributed to the intervention studied. This is known as internal validity. Various types of bias can undermine internal validity. These include:

• Different characteristics between patients participating and those theoretically eligible for study but not participating (selection bias).
• Co-interventions or provision of care apart from the intervention under evaluation (performance bias).
• Differential assessment of outcome (detection bias).
• Occurrence and reporting of patients who do not complete the study (attrition bias).

In principle, rankings of research design have been based on the ability of each study design category to minimize these biases. A randomized controlled trial minimizes systematic bias (in theory) by selecting a sample of participants from a particular population and allocating them randomly to the intervention and control groups. Thus, in general, randomized controlled studies have been typically assigned the greatest strength, followed by non-randomized clinical trials and controlled observational studies. The design, conduct and analysis of trials are important factors as well. For example, a well-designed and conducted observational study with a large sample size may provide stronger evidence than a poorly designed and conducted randomized controlled trial with a small sample size. The following is a representative list of study designs (some of which have alternative names) ranked from most to least methodologically rigorous in their potential ability to minimize systematic bias:

Randomized controlled trials Non-randomized controlled trials Prospective cohort studies Retrospective case control studies Cross-sectional studies Surveillance studies (e.g., using registries or surveys) Consecutive case series Single case reports

When there are merely associations but not causal relationships between a study’s variables and outcomes, it is important not to draw causal inferences. Confounding refers to independent variables that systematically vary with the causal variable. This distorts measurement of the outcome of interest because its effect size is mixed with the effects of other extraneous factors. For observational, and in some cases randomized controlled trials, the method in which confounding factors are handled (either through stratification or appropriate statistical modeling) are of particular concern. For example, in order to interpret and generalize conclusions to our population of Medicare patients, it may be necessary for studies to match or stratify their intervention and control groups by patient age or co-morbidities.

Methodological strength is, therefore, a multidimensional concept that relates to the design, implementation and analysis of a clinical study. In addition, thorough documentation of the conduct of the research, particularly study selection criteria, rate of attrition and process for data collection, is essential for CMS to adequately assess and consider the evidence.

Generalizability of Clinical Evidence to the Medicare Population

The applicability of the results of a study to other populations, settings, treatment regimens and outcomes assessed is known as external validity. Even well-designed and well-conducted trials may not supply the evidence needed if the results of a study are not applicable to the Medicare population. Evidence that provides accurate information about a population or setting not well represented in the Medicare program would be considered but would suffer from limited generalizability.

The extent to which the results of a trial are applicable to other circumstances is often a matter of judgment that depends on specific study characteristics, primarily the patient population studied (age, sex, severity of disease and presence of co-morbidities) and the care setting (primary to tertiary level of care, as well as the experience and specialization of the care provider). Additional relevant variables are treatment regimens (dosage, timing and route of administration), co-interventions or concomitant therapies, and type of outcome and length of follow-up.

The level of care and the experience of the providers in the study are other crucial elements in assessing a study’s external validity. Trial participants in an academic medical center may receive more or different attention than is typically available in non-tertiary settings. For example, an investigator’s lengthy and detailed explanations of the potential benefits of the intervention and/or the use of new equipment provided to the academic center by the study sponsor may raise doubts about the applicability of study findings to community practice.

Given the evidence available in the research literature, some degree of generalization about an intervention’s potential benefits and harms is invariably required in making coverage determinations for the Medicare population. Conditions that assist us in making reasonable generalizations are biologic plausibility, similarities between the populations studied and Medicare patients (age, sex, ethnicity and clinical presentation) and similarities of the intervention studied to those that would be routinely available in community practice.

A study’s selected outcomes are an important consideration in generalizing available clinical evidence to Medicare coverage determinations. One of the goals of our determination process is to assess health outcomes. These outcomes include resultant risks and benefits such as increased or decreased morbidity and mortality. In order to make this determination, it is often necessary to evaluate whether the strength of the evidence is adequate to draw conclusions about the direction and magnitude of each individual outcome relevant to the intervention under study. In addition, it is important that an intervention’s benefits are clinically significant and durable, rather than marginal or short-lived. Generally, an intervention is not reasonable and necessary if its risks outweigh its benefits.

If key health outcomes have not been studied or the direction of clinical effect is inconclusive, we may also evaluate the strength and adequacy of indirect evidence linking intermediate or surrogate outcomes to our outcomes of interest.

Assessing the Relative Magnitude of Risks and Benefits

Generally, an intervention is not reasonable and necessary if its risks outweigh its benefits. Health outcomes are one of several considerations in determining whether an item or service is reasonable and necessary. CMS places greater emphasis on health outcomes actually experienced by patients, such as quality of life, functional status, duration of disability, morbidity and mortality, and less emphasis on outcomes that patients do not directly experience, such as intermediate outcomes, surrogate outcomes, and laboratory or radiographic responses. The direction, magnitude, and consistency of the risks and benefits across studies are also important considerations. Based on the analysis of the strength of the evidence, CMS assesses the relative magnitude of an intervention or technology’s benefits and risk of harm to Medicare beneficiaries.

Patient Population: Enrolled & Treated with Sex Reassignment Surgery Loss of Patients & Missing Data

Panel A (Controlled Studies)

Panel B (Surgical Series: No Concurrent Controls)

Panel C (Mixed Treatment Series: No Direct Control Groups)

*Data obtained via a survey on a website and distributed at a conference B/C=because BSRI=Bem Sex Role Inventory F=Female FP-R=Freiberg Personality Inventory GD=Gender dysphoria GID=Gender identity disorder HADS=Hospital Anxiety & Depression Scale IPP=Inventory of Interpersonal Problems M=Male NA=Not applicable SCL-90=Symptom Checklist-90 SF-36=Short Form 36 GRS=Sex reassignment surgery Tx=Treatment W/o=without

Demographic Features of Study Populations

Psychometric and Satisfaction Survey Instruments

Endpoint Data Types and Sources

Appendix G.

Longitudinal Studies Which Used Patients as Their Own Controls and Which Used Psychometric Tests with Extensive Normative Data or Longitudinal Studies Which Used National Data Sets

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Wise TN, Meyer JK. The border area between transvestism and gender dysphoria: transvestitic applicants for sex reassignment. Arch Sex Behav. 1980 Aug;9(4):327-42. PMID: 7416946.

Wolfradt U, Engelmann S. Depersonalization, fantasies, and coping behavior in clinical context. J Clin Psychol. 1999 Feb;55(2):225-32. PMID: 10100823.

Wolfradt U, Neumann K. Depersonalization, self-esteem and body image in male-to-female transsexuals compared to male and female controls. Arch Sex Behav. 2001 Jun;30(3):301-10 PMID: 11330119.

WPATH 2001 Meyer III W, Bockting WO, Cohen-Kettenis P, Coleman E, DiCeglie D, Devor H, Gooren L, Hage JJ, Kirk S, Kuiper B., Laub D., Lawrence A., Menard Y., Monstrey S, Patton J, Schaefer L., Webb A, Wheeler CC . The Harry Benjamin International Gender Dysphoria Association's Standards Of Care For Gender Identity Disorders. (6 th version) February, 2001. http://www.wpath.org/site_page.cfm?pk_association_webpage_menu=1351&pk_association_webpage=4655.

WPATH 2012 Coleman E, Bockting W, Botzer M, Cohen-Kettenis P, DeCuypere G, Feldman J, Fraser L, Green J, Knudson G, Meyer WJ, Monstrey S, Adler RK, Brown GR, Devor AH, Ehrbar R, Ettner R, Eyler E, Garofalo R, Karasic DH, Istar Lev A, Mayer G, Meyer-Bahlburg H, Paxton Hall B, Pfäfflin F, Rachlin K, Robinson B, Schechter LS, Tangpricha V, van Trotsenburg M, Vitale A, Winter S, Whittle S, Wylie KR, Zucker K. Standards of care for the health of transsexual, transgender, and gender-nonconforming people . (7th version) 2012. http://www.wpath.org/site_page.cfm?pk_association_webpage_menu=1351&pk_association_webpage=3926.

Wroblewski P, Gustafsson J, Selvaggi G. Sex reassignment surgery for transsexuals. Curr Opin Endocrinol Diabetes Obes. 2013 Dec;20(6):570-4. PMID: 24468760.

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Yik Koon, T. (2002). The Mak Nyahs: Malaysian Male to Female Transsexuals . (Chapter 4) Eastern Universities Press.

Zhu, Y, Imperato-McGinley, J, Male Sexual Differentiation Disorder and 5α-Reductase-2 Deficiency. Glob. libr. women's med ., (ISSN: 1756-2228) 2008; DOI 10.3843/GLOWM.10350. (Not in PubMed.)

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Zimmermann A, Zimmer R, Kovacs L, Einödshofer S, Herschbach P, Henrich G, Tunner W, Biemer E, Papadopulos N. [Transsexuals' life satisfaction after gender transformation operations]. Chirurg . 2006 May;77(5):432-8. German. Erratum in Chirurg . 2006 Jun;77(6):530. PMID: 16437228.

Zoni AC, González MA, Sjögren HW. Syphilis in the most at-risk populations in Latin America and the Caribbean: a systematic review. Int J Infect Dis . 2013 Feb;17(2):e84-92. Epub 2012 Oct 12. PMID: 23063547.

Zucker KJ, Bradley SJ, Hughes HE. Gender dysphoria in a child with true hermaphroditism. Can J Psychiatry. 1987 Oct;32(7):602-9. PMID: 3676994.

A-Zucker KJ, Bradley SJ, Kuksis M, Pecore K, Birkenfeld-Adams A, Doering RW, Mitchell JN, Wild J. Gender constancy judgments in children with gender identity disorder: evidence for a developmental lag . Arch Sex Behav . 1999 Dec;28(6):475-502. PMID: 10650437.

B-Zucker KJ. Intersexuality and gender identity differentiation. Annu Rev Sex Res. 1999;10:1-69. PMID: 10895247.

Zucker K, Cohen-Kettenis P, Drescher J, Meyer-Bahlburg H, Pfäfflin F, Womack W. Memo outlining evidence for change for gender identity disorder in the DSM-5. Arch Sex Behav . 2013 Jul;42(5):901-14. PMID: 23868018.

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National Estimates of Gender-Affirming Surgery in the US

Jason d. wright.

1 Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, New York

Yukio Suzuki

Koji matsuo.

2 Department of Obstetrics and Gynecology, University of Southern California, Los Angeles

Dawn L. Hershman

Accepted for Publication: July 15, 2023.

Published: August 23, 2023. doi:10.1001/jamanetworkopen.2023.30348

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2023 Wright JD et al. JAMA Network Open .

Author Contributions: Dr Wright had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Wright, Chen.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Wright.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Wright, Chen.

Administrative, technical, or material support: Wright, Suzuki.

Conflict of Interest Disclosures: Dr Wright reported receiving grants from Merck and personal fees from UpToDate outside the submitted work. No other disclosures were reported.

Data Sharing Statement: See Supplement 2 .

Associated Data

eFigure. Percentage of Patients With Codes for Gender Identity Disorder Who Underwent GAS

This cohort study examines trends in inpatient and outpatient gender-affirming surgical procedures in the US and explores the temporal trends in the types of procedures across age groups.

What are the temporal trends in gender-affirming surgery (GAS) in the US?

In this cohort study of 48 019 patients, GAS increased significantly, nearly tripling from 2016 to 2019. Breast and chest surgery was the most common class of procedures performed overall; genital reconstructive procedures were more common among older individuals.

These findings suggest that there will be a greater need for clinicians knowledgeable in the care of transgender individuals with the requisite expertise to perform gender-affirming procedures.

While changes in federal and state laws mandating coverage of gender-affirming surgery (GAS) may have led to an increase in the number of annual cases, comprehensive data describing trends in both inpatient and outpatient procedures are limited.

To examine trends in inpatient and outpatient GAS procedures in the US and to explore the temporal trends in the types of GAS performed across age groups.

Design, Setting, and Participants

This cohort study includes data from 2016 to 2020 in the Nationwide Ambulatory Surgery Sample and the National Inpatient Sample. Patients with diagnosis codes for gender identity disorder, transsexualism, or a personal history of sex reassignment were identified, and the performance of GAS, including breast and chest procedures, genital reconstructive procedures, and other facial and cosmetic surgical procedures, were identified.

Main Outcome Measures

Weighted estimates of the annual number of inpatient and outpatient procedures performed and the distribution of each class of procedure overall and by age were analyzed.

A total of 48 019 patients who underwent GAS were identified, including 25 099 (52.3%) who were aged 19 to 30 years. The most common procedures were breast and chest procedures, which occurred in 27 187 patients (56.6%), followed by genital reconstruction (16 872 [35.1%]) and other facial and cosmetic procedures (6669 [13.9%]). The absolute number of GAS procedures rose from 4552 in 2016 to a peak of 13 011 in 2019 and then declined slightly to 12 818 in 2020. Overall, 25 099 patients (52.3%) were aged 19 to 30 years, 10 476 (21.8%) were aged 31 to 40, and 3678 (7.7%) were aged12 to 18 years. When stratified by the type of procedure performed, breast and chest procedures made up a greater percentage of the surgical interventions in younger patients, while genital surgical procedures were greater in older patients.

Conclusions and Relevance

Performance of GAS has increased substantially in the US. Breast and chest surgery was the most common group of procedures performed. The number of genital surgical procedures performed increased with increasing age.

Introduction

Gender dysphoria is characterized as an incongruence between an individual’s experienced or expressed gender and the gender that was assigned at birth. 1 Transgender individuals may pursue multiple treatments, including behavioral therapy, hormonal therapy, and gender-affirming surgery (GAS). 2 GAS encompasses a variety of procedures that align an individual patient’s gender identity with their physical appearance. 2 , 3 , 4

While numerous surgical interventions can be considered GAS, the procedures have been broadly classified as breast and chest surgical procedures, facial and cosmetic interventions, and genital reconstructive surgery. 2 , 4 Prior studies 2 , 3 , 4 , 5 , 6 , 7 have shown that GAS is associated with improved quality of life, high rates of satisfaction, and a reduction in gender dysphoria. Furthermore, some studies have reported that GAS is associated with decreased depression and anxiety. 8 Lastly, the procedures appear to be associated with acceptable morbidity and reasonable rates of perioperative complications. 2 , 4

Given the benefits of GAS, the performance of GAS in the US has increased over time. 9 The increase in GAS is likely due in part to federal and state laws requiring coverage of transition-related care, although actual insurance coverage of specific procedures is variable. 10 , 11 While prior work has shown that the use of inpatient GAS has increased, national estimates of inpatient and outpatient GAS are lacking. 9 This is important as many GAS procedures occur in ambulatory settings. We performed a population-based analysis to examine trends in GAS in the US and explored the temporal trends in the types of GAS performed across age groups.

Data Sources

To capture both inpatient and outpatient surgical procedures, we used data from the Nationwide Ambulatory Surgery Sample (NASS) and the National Inpatient Sample (NIS). NASS is an ambulatory surgery database and captures major ambulatory surgical procedures at nearly 2800 hospital-owned facilities from up to 35 states, approximating a 63% to 67% stratified sample of hospital-owned facilities. NIS comprehensively captures approximately 20% of inpatient hospital encounters from all community hospitals across 48 states participating in the Healthcare Cost and Utilization Project (HCUP), covering more than 97% of the US population. Both NIS and NASS contain weights that can be used to produce US population estimates. 12 , 13 Informed consent was waived because data sources contain deidentified data, and the study was deemed exempt by the Columbia University institutional review board. This cohort study followed the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline.

Patients and Procedures

We selected patients of all ages with an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision ( ICD-10 ) diagnosis codes for gender identity disorder or transsexualism ( ICD-10 F64) or a personal history of sex reassignment ( ICD-10 Z87.890) from 2016 to 2020 (eTable in Supplement 1 ). We first examined all hospital (NIS) and ambulatory surgical (NASS) encounters for patients with these codes and then analyzed encounters for GAS within this cohort. GAS was identified using ICD-10 procedure codes and Common Procedural Terminology codes and classified as breast and chest procedures, genital reconstructive procedures, and other facial and cosmetic surgical procedures. 2 , 4 Breast and chest surgical procedures encompassed breast reconstruction, mammoplasty and mastopexy, or nipple reconstruction. Genital reconstructive procedures included any surgical intervention of the male or female genital tract. Other facial and cosmetic procedures included cosmetic facial procedures and other cosmetic procedures including hair removal or transplantation, liposuction, and collagen injections (eTable in Supplement 1 ). Patients might have undergone procedures from multiple different surgical groups. We measured the total number of procedures and the distribution of procedures within each procedural group.

Within the data sets, sex was based on patient self-report. The sex of patients in NIS who underwent inpatient surgery was classified as either male, female, missing, or inconsistent. The inconsistent classification denoted patients who underwent a procedure that was not consistent with the sex recorded on their medical record. Similar to prior analyses, patients in NIS with a sex variable not compatible with the procedure performed were classified as having undergone genital reconstructive surgery (GAS not otherwise specified). 9

Clinical variables in the analysis included patient clinical and demographic factors and hospital characteristics. Demographic characteristics included age at the time of surgery (12 to 18 years, 19 to 30 years, 31 to 40 years, 41 to 50 years, 51 to 60 years, 61 to 70 years, and older than 70 years), year of the procedure (2016-2020), and primary insurance coverage (private, Medicare, Medicaid, self-pay, and other). Race and ethnicity were only reported in NIS and were classified as White, Black, Hispanic and other. Race and ethnicity were considered in this study because prior studies have shown an association between race and GAS. The income status captured national quartiles of median household income based of a patient’s zip code and was recorded as less than 25% (low), 26% to 50% (medium-low), 51% to 75% (medium-high), and 76% or more (high). The Elixhauser Comorbidity Index was estimated for each patient based on the codes for common medical comorbidities and weighted for a final score. 14 Patients were classified as 0, 1, 2, or 3 or more. We separately reported coding for HIV and AIDS; substance abuse, including alcohol and drug abuse; and recorded mental health diagnoses, including depression and psychoses. Hospital characteristics included a composite of teaching status and location (rural, urban teaching, and urban nonteaching) and hospital region (Northeast, Midwest, South, and West). Hospital bed sizes were classified as small, medium, and large. The cutoffs were less than 100 (small), 100 to 299 (medium), and 300 or more (large) short-term acute care beds of the facilities from NASS and were varied based on region, urban-rural designation, and teaching status of the hospital from NIS. 8 Patients with missing data were classified as the unknown group and were included in the analysis.

Statistical Analysis

National estimates of the number of GAS procedures among all hospital encounters for patients with gender identity disorder were derived using discharge or encounter weight provided by the databases. 15 The clinical and demographic characteristics of the patients undergoing GAS were reported descriptively. The number of encounters for gender identity disorder, the percentage of GAS procedures among those encounters, and the absolute number of each procedure performed over time were estimated. The difference by age group was examined and tested using Rao-Scott χ 2 test. All hypothesis tests were 2-sided, and P  < .05 was considered statistically significant. All analyses were conducted using SAS version 9.4 (SAS Institute Inc).

A total of 48 019 patients who underwent GAS were identified ( Table 1 ). Overall, 25 099 patients (52.3%) were aged 19 to 30 years, 10 476 (21.8%) were aged 31 to 40, and 3678 (7.7%) were aged 12 to 18 years. Private insurance coverage was most common in 29 064 patients (60.5%), while 12 127 (25.3%) were Medicaid recipients. Depression was reported in 7192 patients (15.0%). Most patients (42 467 [88.4%]) were treated at urban, teaching hospitals, and there was a disproportionate number of patients in the West (22 037 [45.9%]) and Northeast (12 396 [25.8%]). Within the cohort, 31 668 patients (65.9%) underwent 1 procedure while 13 415 (27.9%) underwent 2 procedures, and the remainder underwent multiple procedures concurrently ( Table 1 ).

The overall number of health system encounters for gender identity disorder rose from 13 855 in 2016 to 38 470 in 2020. Among encounters with a billing code for gender identity disorder, there was a consistent rise in the percentage that were for GAS from 4552 (32.9%) in 2016 to 13 011 (37.1%) in 2019, followed by a decline to 12 818 (33.3%) in 2020 ( Figure 1 and eFigure in Supplement 1 ). Among patients undergoing ambulatory surgical procedures, 37 394 (80.3%) of the surgical procedures included gender-affirming surgical procedures. For those with hospital admissions with gender identity disorder, 10 625 (11.8%) of admissions were for GAS.

Error bars represent 95% CIs. GAS indicates gender-affirming surgery.

Breast and chest procedures were most common and were performed for 27 187 patients (56.6%). Genital reconstruction was performed for 16 872 patients (35.1%), and other facial and cosmetic procedures for 6669 patients (13.9%) ( Table 2 ). The most common individual procedure was breast reconstruction in 21 244 (44.2%), while the most common genital reconstructive procedure was hysterectomy (4489 [9.3%]), followed by orchiectomy (3425 [7.1%]), and vaginoplasty (3381 [7.0%]). Among patients who underwent other facial and cosmetic procedures, liposuction (2945 [6.1%]) was most common, followed by rhinoplasty (2446 [5.1%]) and facial feminizing surgery and chin augmentation (1874 [3.9%]).

Abbreviations: GAS, gender-affirming surgery; NA, not available; NOS, not otherwise specified.

The absolute number of GAS procedures rose from 4552 in 2016 to a peak of 13 011 in 2019 and then declined slightly to 12 818 in 2020 ( Figure 1 ). Similar trends were noted for breast and chest surgical procedures as well as genital surgery, while the rate of other facial and cosmetic procedures increased consistently from 2016 to 2020. The distribution of the individual procedures performed in each class were largely similar across the years of analysis ( Table 3 ).

Abbreviations: GAS, gender-affirming surgery; NOS, not otherwise specified.

When stratified by age, patients 19 to 30 years had the greatest number of procedures, 25 099 ( Figure 2 ). There were 10 476 procedures performed in those aged 31 to 40 years and 4359 in those aged 41 to 50 years. Among patients younger than 19 years, 3678 GAS procedures were performed. GAS was less common in those cohorts older than 50 years. Overall, the greatest number of breast and chest surgical procedures, genital surgical procedures, and facial and other cosmetic surgical procedures were performed in patients aged 19 to 30 years.

Percentages are based on the number of procedures divided by number of patients; thus, as some patients underwent multiple procedures the total may be greater than 100%. Error bars represent 95% CIs.

When stratified by the type of procedure performed, breast and chest procedures made up the greatest percentage of the surgical interventions in younger patients while genital surgical procedures were greater in older patients ( Figure 2 ). Additionally, 3215 patients (87.4%) aged 12 to 18 years underwent GAS and had breast or chest procedures. This decreased to 16 067 patients (64.0%) in those aged 19 to 30 years, 4918 (46.9%) in those aged 31 to 40 years, and 1650 (37.9%) in patients aged 41 to 50 years ( P  < .001). In contrast, 405 patients (11.0%) aged 12 to 18 years underwent genital surgery. The percentage of patients who underwent genital surgery rose sequentially to 4423 (42.2%) in those aged 31 to 40 years, 1546 (52.3%) in those aged 51 to 60 years, and 742 (58.4%) in those aged 61 to 70 years ( P  < .001). The percentage of patients who underwent facial and other cosmetic surgical procedures rose with age from 9.5% in those aged 12 to 18 years to 20.6% in those aged 51 to 60 years, then gradually declined ( P  < .001). Figure 2 displays the absolute number of procedure classes performed by year stratified by age. The greatest magnitude of the decline in 2020 was in younger patients and for breast and chest procedures.

These findings suggest that the number of GAS procedures performed in the US has increased dramatically, nearly tripling from 2016 to 2019. Breast and chest surgery is the most common class of procedure performed while patients are most likely to undergo surgery between the ages of 19 and 30 years. The number of genital surgical procedures performed increased with increasing age.

Consistent with prior studies, we identified a remarkable increase in the number of GAS procedures performed over time. 9 , 16 A prior study examining national estimates of inpatient GAS procedures noted that the absolute number of procedures performed nearly doubled between 2000 to 2005 and from 2006 to 2011. In our analysis, the number of GAS procedures nearly tripled from 2016 to 2020. 9 , 17 Not unexpectedly, a large number of the procedures we captured were performed in the ambulatory setting, highlighting the need to capture both inpatient and outpatient procedures when analyzing data on trends. Like many prior studies, we noted a decrease in the number of procedures performed in 2020, likely reflective of the COVID-19 pandemic. 18 However, the decline in the number of procedures performed between 2019 and 2020 was relatively modest, particularly as these procedures are largely elective.

Analysis of procedure-specific trends by age revealed a number of important findings. First, GAS procedures were most common in patients aged 19 to 30 years. This is in line with prior work that demonstrated that most patients first experience gender dysphoria at a young age, with approximately three-quarters of patients reporting gender dysphoria by age 7 years. These patients subsequently lived for a mean of 23 years for transgender men and 27 years for transgender women before beginning gender transition treatments. 19 Our findings were also notable that GAS procedures were relatively uncommon in patients aged 18 years or younger. In our cohort, fewer than 1200 patients in this age group underwent GAS, even in the highest volume years. GAS in adolescents has been the focus of intense debate and led to legislative initiatives to limit access to these procedures in adolescents in several states. 20 , 21

Second, there was a marked difference in the distribution of procedures in the different age groups. Breast and chest procedures were more common in younger patients, while genital surgery was more frequent in older individuals. In our cohort of individuals aged 19 to 30 years, breast and chest procedures were twice as common as genital procedures. Genital surgery gradually increased with advancing age, and these procedures became the most common in patients older than 40 years. A prior study of patients with commercial insurance who underwent GAS noted that the mean age for mastectomy was 28 years, significantly lower than for hysterectomy at age 31 years, vaginoplasty at age 40 years, and orchiectomy at age 37 years. 16 These trends likely reflect the increased complexity of genital surgery compared with breast and chest surgery as well as the definitive nature of removal of the reproductive organs.

Limitations

This study has limitations. First, there may be under-capture of both transgender individuals and GAS procedures. In both data sets analyzed, gender is based on self-report. NIS specifically makes notation of procedures that are considered inconsistent with a patient’s reported gender (eg, a male patient who underwent oophorectomy). Similar to prior work, we assumed that patients with a code for gender identity disorder or transsexualism along with a surgical procedure classified as inconsistent underwent GAS. 9 Second, we captured procedures commonly reported as GAS procedures; however, it is possible that some of these procedures were performed for other underlying indications or diseases rather than solely for gender affirmation. Third, our trends showed a significant increase in procedures through 2019, with a decline in 2020. The decline in services in 2020 is likely related to COVID-19 service alterations. Additionally, while we comprehensively captured inpatient and ambulatory surgical procedures in large, nationwide data sets, undoubtedly, a small number of procedures were performed in other settings; thus, our estimates may underrepresent the actual number of procedures performed each year in the US.

Conclusions

These data have important implications in providing an understanding of the use of services that can help inform care for transgender populations. The rapid rise in the performance of GAS suggests that there will be a greater need for clinicians knowledgeable in the care of transgender individuals and with the requisite expertise to perform GAS procedures. However, numerous reports have described the political considerations and challenges in the delivery of transgender care. 22 Despite many medical societies recognizing the necessity of gender-affirming care, several states have enacted legislation or policies that restrict gender-affirming care and services, particularly in adolescence. 20 , 21 These regulations are barriers for patients who seek gender-affirming care and provide legal and ethical challenges for clinicians. As the use of GAS increases, delivering equitable gender-affirming care in this complex landscape will remain a public health challenge.

Supplement 1.

eTable. ICD-10 and CPT Codes of Gender-Affirming Surgery

Supplement 2.

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Identity Document Laws and Policies

• State uses easy to understand form and does not require provider certification ( 21 states + D.C. )
• State uses easy to understand form and requires provider certification (accepted from wide range of professionals) ( 7 states, 1 territory )
• State uses easy to understand form and requires provider certification (accepted from limited range of professionals) ( 3 states )
• State has no form. No court order or proof of surgery required, but burdensome process requirements and/or provider certification required from limited range of professionals ( 4 states )
• State has unclear, unknown or unwritten policy regarding gender marker changes ( 3 states, 2 territories )
• State requires proof of surgery, court order, or amended birth certificate ( 9 states, 2 territories )
• State does not allow for updating the gender marker on driver's license ( 3 states )

Percent of Transgender Population Covered by Laws

*Note: These percentages reflect estimates of the transgender population (ages 18+) living in the 50 states and the District of Columbia. Estimates of transgender people in the U.S. territories are not available, and so cannot be reflected here. Population estimates are from The Williams Institute .

51 % of transgender people (ages 18+) live in states that allow residents to mark M, F, or X on their driver's license

50 % of transgender people (ages 18+) live in states with an easy to understand form and no provider certification required

11 % of transgender people (ages 18+) live in states with an easy to understand form and provider certification requirements (accepted from wide range of professionals)

3 % of transgender people (ages 18+) live in states with an easy to understand form and provider certification requirements (accepted from limited range of professionals)

6 % of transgender people (ages 18+) live in states with no form; no court order or proof of surgery required, but burdensome process and/or provider certification requirements

3 % of transgender people (ages 18+) live in states with an unclear, unknown, or unwritten policy regarding the process of gender marker changes

18 % of transgender people (ages 18+) live in states that require proof of surgery, court order, and/or amended birth certificate to change gender marker

10 % of transgender people (ages 18+) live in states that do not allow for updating the gender marker on the driver’s license

• State issues new birth certificate and does not require sex reassignment surgery nor court order in order to change gender marker ( 26 states , 1 territory + D.C. )
• State is unclear regarding medical requirements and/or may require a court order to change gender marker ( 4 states, 1 territory )
• State requires proof of sex reassignment surgery in order to change gender marker ( 12 states, 1 territory )
• State does not allow for amending the gender marker on the birth certificate ( 5 states )

41 % of transgender people (ages 18+) live in states that allow residents to mark M, F, or X on their birth certificates

64 % of transgender people (ages 18+) live in states that issue new birth certificates and do not require sex reassignment surgery nor court order in order to change gender marker

11 % of transgender people (ages 18+) live in states that are unclear regarding medical requirements and/or may require a court order to change gender marker

4 % of transgender people (ages 18+) live in states have unclear, unknown or unwritten policy regarding gender marker changes

16 % of transgender people (ages 18+) live in states require proof of sex reassignment surgery in order to change gender marker

5 % of transgender people (ages 18+) live in states that do not allow for amending the gender marker on the birth certificate

• State law does not require publication of name change announcement ( 25 states , 1 territory + D.C. )
• State law has unclear publication requirement, or requires publication but allows individual court discretion and/or broad option to waive requirement ( 16 states )
• State law requires publication of name change announcement ( 9 states, 4 territories )

61 % of transgender people (ages 18+) live in states that do not require publication of name change announcement

26 % of transgender people (ages 18+) live in states with unclear requirements, individual court discretion, or broad waiver options for public announcement of a name change

13 % of transgender people (ages 18+) live in states that require publication of name change announcement

66 % of transgender people (ages 18+) live in states with additional restrictions and/or requirements for individuals with a criminal record

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The term “sexual orientation” is loosely defined as a person’s pattern of romantic or sexual attraction to people of the opposite sex or gender, the same sex or gender, or more than one sex or gender. Laws that explicitly mention sexual orientation primarily protect or harm lesbian, gay, and bisexual people. That said, transgender people who are lesbian, gay or bisexual can be affected by laws that explicitly mention sexual orientation.

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“Gender identity” is a person’s deeply-felt inner sense of being male, female, or something else or in-between. “Gender expression” refers to a person’s characteristics and behaviors such as appearance, dress, mannerisms and speech patterns that can be described as masculine, feminine, or something else. Gender identity and expression are independent of sexual orientation, and transgender people may identify as heterosexual, lesbian, gay or bisexual. Laws that explicitly mention “gender identity” or “gender identity and expression” primarily protect or harm transgender people. These laws also can apply to people who are not transgender, but whose sense of gender or manner of dress does not adhere to gender stereotypes.

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Sex, gender identity, trans status - data collection and publication: guidance

Guidance for public bodies on the collection of data on sex and gender.

I was asked by the then Cabinet Secretary for Social Security and Older People to bring together a working group to look at the way data on sex and gender is collected and published, and put together guidance for public bodies.

This was announced at the same time as the Cabinet Secretary updated Scottish Parliament on plans to reform the Gender Recognition Act 2004 in Scotland. While the two are not directly related, some groups had, in response to the proposals to reform gender recognition, raised concerns about the collection and use of data by sex and gender.

The scope of this work is about data collected and used by Scottish public bodies – for operational, statistical and research purposes. It is separate from Scotland's Census 2022.

The book "Invisible Women" by Caroline Criado Perez, and work by a number of organisations, has also drawn attention to the frequency with which data is neither collected, aggregated or used in a way that takes account of the differences including biological and physical differences – between men and women, and their impact in areas such as transport, health and access to services.

I have brought together a group of experts in collecting and presenting data from across the UK . I have listened to the varied views and drawn my own conclusions from these. An important part of this work was making sure that the guidance is informed by evidence from a wide range of individuals and organisations with views based on a lived experience of these issues. To do this, I met a number of external stakeholders to listen to their views, as well as holding public engagement events to give everyone with an interest the opportunity to have their views heard. Finally, a public consultation was held on a draft version of this guidance.

I gathered together these insights and considered them when putting together this guidance.

Given the importance of this topic, it was important for me to carry out this work in a transparent way, so that people can see how it has been put together. To this end, I have been posting regular blog updates on my Statistics blog, as well as publishing all minutes from the working group meetings on the Scottish Government website.

My role as Chief Statistician brings with it responsibility for the coordination and implementation of professional statistical standards that help maintain trustworthiness in the use of data, its quality, and delivering improved outcomes for people in Scotland. In putting together this guidance I have, therefore, rooted the work in a set of widely accepted statistical principles. Whilst the concepts behind definitions are important, so too is having data that is high quality, and can be used to drive changes and improvements that will save time, money and lives – for the benefit of everyone.

Roger Halliday, Chief Statistician

Email: [email protected]

Update to section on collecting data on non-binary groups to include reference to Non-binary Action Plan.

Section 13 added following the publication of new guidance from the Office for Statistics Regulation.

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FACT CHECK: Is The Rate Of Regret After Gender-Affirming Surgery Only 1%?

A post shared on social media  claims only 1% of people regret their gender-affirmation surgery.

  View this post on Instagram   A post shared by matt bernstein (@mattxiv)

Verdict: Misleading

While the study cited does find a 1% regret rate, it and other subsequent studies share disclaimers and the limitations of research, suggesting the rate may actually be higher.

Fact Check:

The Instagram post claims that only 1% of patients regret their gender transition surgeries. The source used is “Regret after Gender-affirmation Surgery: A systematic Review and Meta-analysis of Prevalence” from the National Library of Medicine (NLM).

The caption is misleading, due to several factors and lack of research that were identified by the study itself and other subsequent papers. (RELATED: Did Canada Release A New Passport That Features Pride Flags?)

This study did not conduct original research, but rather compiled research done in many different places which resulted in a disclaimer warning of the danger of generalizing the results. “There is high subjectivity in the assessment of regret and lack of standardized questionnaires,” which varies from study to study, according to the NLM document.

The study quotes a 2017 study published in the Journal of Sex and Marital Therapy , which conducted a follow-up survey of regret among patients after their transition. The study notes a major limitation was that few patients followed up after surgery.

“This study’s main limitation was the sample representativeness. With a response rate of 37%, similar to the attrition rates of most follow-up studies,” according to the study. Out of the response rate, six percent reported dissatisfaction or regret with the surgery, the study claims.

Additional data found in a Cambridge University Press study showed subjects on average do not express regret in the transition until an average of 10 years after their surgery. The study also claimed twelve cases out of the 175 selected, or around seven percent, had expressed detransitioning.

“There is some evidence that people detransition on average 4 or 8 years after completion of transition, with regret expressed after 10 years,” the study suggests. It also states that the actual rate is unknown, with some ranging up to eight percent.

Another study published in 2007 from Sweden titled, “ Factors predictive of regret in sex reassignment ,” found that around four percent of patients who underwent sex reassignment surgery between 1972-1992 regretted the measures taken. The research was done over 10 years after the the procedures.

The National Library of Medicine study only includes individuals who underwent transition surgery and does not take into account regret rates among individuals who took hormone replacement. Research from The Journal of Clinical Endocrinology and Metabolism (JCEM) found that the hormone continuation rate was 70 percent, suggesting nearly 30 percent discontinued their hormone treatment for a variety of reasons.

“In the largest surgery study, approximately 1% of patients regretted having gender-confirmation surgery,” Christina Roberts, M.D, a professor of Pediatrics at the University of Missouri-Kansas City School of Medicine and a participant for the study for the JCEM, told Check Your Fact via email.

Roberts stated that while there were multiple major factors in regards to those regretting the surgery, including poor cosmetic outcome and lack of social support, she claimed discontinuation of hormone therapies and other treatment are “not the same thing as regret.”

“This is an apples to oranges comparison,” Roberts added. (RELATED: Is Disney World Replacing The American Flag With The LGBTQ+ Pride Flag In June 2023?)

Check Your Fact reached out to multiple doctors and researchers associated with the above and other studies and will update this piece if responses are provided.

Joseph Casieri

Fact check reporter.

5 most common reasons people seek gender reassignment surgery

• By Health IQ digital
• Jul 03, 2024

Gender reassignment surgery, also known as a sex change, is a deeply personal and significant decision that many individuals make to align their physical appearance with their gender identity. This life-changing process involves a series of medical procedures that transform an individual’s physical attributes to match their identified gender. While the decision to undergo a sex change is unique to each person, certain common reasons often motivate this transformative journey. Understanding these reasons can provide insight into the experiences and challenges faced by transgender individuals.

Gender dysphoria

One of the most prevalent reasons people seek a sex change is gender dysphoria. This condition is characterized by a profound sense of discomfort or distress due to a mismatch between an individual’s gender identity and their assigned sex at birth. Gender dysphoria can lead to significant emotional and psychological distress, affecting one’s mental health and overall well-being. For many, transitioning through a gender reassignment surgery is a critical step in alleviating the intense feelings of incongruence and achieving a sense of alignment with their true self.

The impact of gender dysphoria

The impact of gender dysphoria can be far-reaching, influencing various aspects of an individual’s life. Many individuals report feeling trapped in a body that does not reflect their true gender, leading to anxiety, depression and social isolation. The process of transitioning can provide immense relief and a sense of liberation, allowing individuals to live authentically and comfortably in their own skin.

Authentic self-expression

Another common reason people seek gender reassignment surgery is the desire for authentic self-expression. For many transgender individuals, living in a body that does not match their gender identity can feel like living a lie. The journey of transitioning allows individuals to express themselves genuinely, both physically and emotionally. This authenticity can foster greater self-esteem, confidence and overall happiness.

The role of self-expression in transitioning

Authentic self-expression goes beyond physical changes; it encompasses the ability to present oneself in a way that aligns with one’s true identity. This might include changes in clothing, hairstyle, voice and behavior. By aligning their external appearance with their internal sense of self, transgender individuals can experience a profound sense of congruence and fulfillment.

Social and legal recognition

The pursuit of social and legal recognition is another significant motivator for those seeking gender reassignment surgery. In many societies, being recognized and treated as one’s identified gender is crucial for navigating everyday life and accessing various rights and privileges. Legal recognition — such as changing one’s name and gender marker on official documents — can help individuals feel validated and respected in their gender identity.

Challenges in achieving recognition

Achieving social and legal recognition can be challenging, as societal attitudes and legal frameworks vary widely across different regions. Transgender individuals often face discrimination and barriers when seeking to update their identification documents or gain acceptance in their communities. However, the process of transitioning can empower individuals to advocate for their rights and seek the recognition they deserve.

Improved mental health

Mental health improvements are a compelling reason for many to undergo gender reassignment surgery. The mental health struggles associated with gender dysphoria and living inauthentically can be severe, often leading to depression, anxiety and suicidal ideation. Transitioning can significantly improve mental health outcomes by reducing the distress caused by gender incongruence and enabling individuals to live more fulfilling lives.

The mental health benefits of transitioning

Research has shown that transitioning can have positive effects on mental health, including reduced symptoms of depression and anxiety, increased life satisfaction and improved overall well-being. By aligning their physical appearance with their gender identity, transgender individuals can experience a greater sense of peace and contentment.

Personal relationships

The desire to improve personal relationships is another reason why people seek gender reassignment surgery. Gender dysphoria and living in a body that does not match one’s identity can strain relationships with family, friends and romantic partners. Transitioning can help individuals build more authentic and meaningful connections with others, as they are able to present themselves genuinely and without the burden of hiding their true identity.

Navigating relationships during transition

Navigating relationships during and after transitioning can be complex, as it often requires education, understanding and support from loved ones. Open communication and a willingness to adapt are crucial for maintaining healthy relationships. For many, the journey of transitioning strengthens their connections with others, leading to more supportive and fulfilling personal relationships.

The profound impact of gender reassignment surgery

The decision to undergo gender reassignment surgery is multifaceted and deeply personal, driven by a range of factors including gender dysphoria, the desire for authentic self-expression, the pursuit of social and legal recognition, improved mental health and the enhancement of personal relationships. Each individual’s journey is unique, yet the common threads that connect these experiences highlight the profound impact of aligning one’s physical appearance with their gender identity.

As society continues to evolve in its understanding and acceptance of transgender individuals, it is essential to recognize and support the diverse reasons that lead people to seek gender reassignment surgery. By doing so, we can foster a more inclusive and compassionate world where everyone has the opportunity to live authentically and with dignity .

This story was created using AI technology.

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• gender dysphoria , gender reassignment surgery , legal recognition , mental health , News2 , personal relationships , sex change , social recognition , transgender individuals , transitioning

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Owner Explains Why Her Male Cat Had ‘Gender Reassignment Surgery’

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A pet owner has gained viral attention after revealing the procedure her cat had that is often likened to human gender-reassignment surgery.

In a video shared on June 5 on TikTok , which has received more than 1.3 million views, Charlie Chronis from Los Angeles shared footage of her cat Siegfried, joking that he had “gender reassignment surgery.”

“[It is] funny that it’s garnered so much attention—it’s honestly a pretty common surgery for male cats,” Chronis told Newsweek . The Siamese mixed-breed cat underwent a perineal ureterostomy, often abbreviated as PU surgery, which is a solution for cats with a blockage in their urinary tract. The surgery creates a new urinary opening, decreasing the length of the urethra and allowing urine to bypass this narrowed region.

The surgery is often recommended when a urethral obstruction within the penis cannot be removed through medical therapy, and in cases of recurrent urethral obstructions. For many male cats, this surgery can be lifesaving, allowing them to live healthier, more comfortable lives.

“He had kidney stones , which led to persistent urinary tract infections and, after treating him with a catheter three times, this was the final solution,” Chronis said.

In serious cases, urinary blockages in cats can prevent them from urinating completely. Life-threatening consequences can occur in as little as 12 to 24 hours of being unable to urinate, and death from untreated obstruction may occur in 36 to 48 hours.

Thanks to the PU surgery, which makes the male cat’s urethra more similar to a female’s, the risk of future blockages will be reduced.

A month and a half after his operation, Siegfried is back to his normal, playful self. “I thought my situation was hilarious and unimaginable, leading me to post my video,” said Chronis. “[I] didn’t realize how many other cats have gone through a similar experience.”

The video prompted lots of responses online from people who were amazed to learn about the procedure.

BrightBlueEyes posted, “I never knew this was a thing,” while Mary wrote: “We adopted a cat like this and named him RuPawl.”

“I’ve got a trans kitty too!” commented Ginabutcherr.

Someone who sees the procedure often weighed in too, as A_scho posted: “Vet tech here… This is hilarious.”

RecklessRoca wrote: “Omg [oh my God] I know someone whose cat had this and we thought it was a one-time deal.”

Do you have funny and adorable videos or pictures of your pet you want to share? Send them to [email protected] with some details about your best friend, and they could appear in our Pet of the Week lineup.

Uncommon Knowledge

Newsweek is committed to challenging conventional wisdom and finding connections in the search for common ground.

The post Owner Explains Why Her Male Cat Had ‘Gender Reassignment Surgery’ appeared first on Newsweek .

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