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Gender Confirmation Surgery (GCS)

What is Gender Confirmation Surgery?

• Transfeminine Tr

Transmasculine Transition

• Traveling Abroad

Choosing a Surgeon

Gender confirmation surgery (GCS), known clinically as genitoplasty, are procedures that surgically confirm a person's gender by altering the genitalia and other physical features to align with their desired physical characteristics. Gender confirmation surgeries are also called gender affirmation procedures. These are both respectful terms.

Gender dysphoria , an experience of misalignment between gender and sex, is becoming more widely diagnosed.  People diagnosed with gender dysphoria are often referred to as "transgender," though one does not necessarily need to experience gender dysphoria to be a member of the transgender community. It is important to note there is controversy around the gender dysphoria diagnosis. Many disapprove of it, noting that the diagnosis suggests that being transgender is an illness.

Ellen Lindner / Verywell

Transfeminine Transition

Transfeminine is a term inclusive of trans women and non-binary trans people assigned male at birth.

Gender confirmation procedures that a transfeminine person may undergo include:

• Penectomy is the surgical removal of external male genitalia.
• Orchiectomy is the surgical removal of the testes.
• Vaginoplasty is the surgical creation of a vagina.
• Feminizing genitoplasty creates internal female genitalia.
• Breast implants create breasts.
• Gluteoplasty increases buttock volume.
• Chondrolaryngoplasty is a procedure on the throat that can minimize the appearance of Adam's apple .

Feminizing hormones are commonly used for at least 12 months prior to breast augmentation to maximize breast growth and achieve a better surgical outcome. They are also often used for approximately 12 months prior to feminizing genital surgeries.

Facial feminization surgery (FFS) is often done to soften the lines of the face. FFS can include softening the brow line, rhinoplasty (nose job), smoothing the jaw and forehead, and altering the cheekbones. Each person is unique and the procedures that are done are based on the individual's need and budget,

Transmasculine is a term inclusive of trans men and non-binary trans people assigned female at birth.

Gender confirmation procedures that a transmasculine person may undergo include:

• Masculinizing genitoplasty is the surgical creation of external genitalia. This procedure uses the tissue of the labia to create a penis.
• Phalloplasty is the surgical construction of a penis using a skin graft from the forearm, thigh, or upper back.
• Metoidioplasty is the creation of a penis from the hormonally enlarged clitoris.
• Scrotoplasty is the creation of a scrotum.

Procedures that change the genitalia are performed with other procedures, which may be extensive.

The change to a masculine appearance may also include hormone therapy with testosterone, a mastectomy (surgical removal of the breasts), hysterectomy (surgical removal of the uterus), and perhaps additional cosmetic procedures intended to masculinize the appearance.

Paying For Gender Confirmation Surgery

Medicare and some health insurance providers in the United States may cover a portion of the cost of gender confirmation surgery.

It is unlawful to discriminate or withhold healthcare based on sex or gender. However, many plans do have exclusions.

For most transgender individuals, the burden of financing the procedure(s) is the main difficulty in obtaining treatment. The cost of transitioning can often exceed $100,000 in the United States, depending upon the procedures needed.

A typical genitoplasty alone averages about $18,000. Rhinoplasty, or a nose job, averaged $5,409 in 2019.  

Traveling Abroad for GCS

Some patients seek gender confirmation surgery overseas, as the procedures can be less expensive in some other countries. It is important to remember that traveling to a foreign country for surgery, also known as surgery tourism, can be very risky.

Regardless of where the surgery will be performed, it is essential that your surgeon is skilled in the procedure being performed and that your surgery will be performed in a reputable facility that offers high-quality care.

When choosing a surgeon , it is important to do your research, whether the surgery is performed in the U.S. or elsewhere. Talk to people who have already had the procedure and ask about their experience and their surgeon.

Before and after photos don't tell the whole story, and can easily be altered, so consider asking for a patient reference with whom you can speak.

It is important to remember that surgeons have specialties and to stick with your surgeon's specialty. For example, you may choose to have one surgeon perform a genitoplasty, but another to perform facial surgeries. This may result in more expenses, but it can result in a better outcome.

A Word From Verywell

Gender confirmation surgery is very complex, and the procedures that one person needs to achieve their desired result can be very different from what another person wants.

Each individual's goals for their appearance will be different. For example, one individual may feel strongly that breast implants are essential to having a desirable and feminine appearance, while a different person may not feel that breast size is a concern. A personalized approach is essential to satisfaction because personal appearance is so highly individualized.

Davy Z, Toze M. What is gender dysphoria? A critical systematic narrative review . Transgend Health . 2018;3(1):159-169. doi:10.1089/trgh.2018.0014

Morrison SD, Vyas KS, Motakef S, et al. Facial Feminization: Systematic Review of the Literature . Plast Reconstr Surg. 2016;137(6):1759-70. doi:10.1097/PRS.0000000000002171

Hadj-moussa M, Agarwal S, Ohl DA, Kuzon WM. Masculinizing Genital Gender Confirmation Surgery . Sex Med Rev . 2019;7(1):141-155. doi:10.1016/j.sxmr.2018.06.004

Dowshen NL, Christensen J, Gruschow SM. Health Insurance Coverage of Recommended Gender-Affirming Health Care Services for Transgender Youth: Shopping Online for Coverage Information . Transgend Health . 2019;4(1):131-135. doi:10.1089/trgh.2018.0055

American Society of Plastic Surgeons. Rhinoplasty nose surgery .

Rights Group: More U.S. Companies Covering Cost of Gender Reassignment Surgery. CNS News. http://cnsnews.com/news/article/rights-group-more-us-companies-covering-cost-gender-reassignment-surgery

The Sex Change Capital of the US. CBS News. http://www.cbsnews.com/2100-3445_162-4423154.html

By Jennifer Whitlock, RN, MSN, FN Jennifer Whitlock, RN, MSN, FNP-C, is a board-certified family nurse practitioner. She has experience in primary care and hospital medicine.

• Patient Care & Health Information
• Diseases & Conditions
• Gender dysphoria

Your health care provider might make a diagnosis of gender dysphoria based on:

• Behavioral health evaluation. Your provider will evaluate you to confirm the presence of gender dysphoria and document how prejudice and discrimination due to your gender identity (minority stress factors) impact your mental health. Your provider will also ask about the degree of support you have from family, chosen family and peers.
• DSM-5. Your mental health professional may use the criteria for gender dysphoria listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), published by the American Psychiatric Association.

Gender dysphoria is different from simply not conforming to stereotypical gender role behavior. It involves feelings of distress due to a strong, pervasive desire to be another gender.

Some adolescents might express their feelings of gender dysphoria to their parents or a health care provider. Others might instead show symptoms of a mood disorder, anxiety or depression. Or they might experience social or academic problems.

• Care at Mayo Clinic

Our caring team of Mayo Clinic experts can help you with your gender dysphoria-related health concerns Start Here

Treatment can help people who have gender dysphoria explore their gender identity and find the gender role that feels comfortable for them, easing distress. However, treatment should be individualized. What might help one person might not help another.

Treatment options might include changes in gender expression and role, hormone therapy, surgery, and behavioral therapy.

If you have gender dysphoria, seek help from a doctor who has expertise in the care of gender-diverse people.

When coming up with a treatment plan, your provider will screen you for mental health concerns that might need to be addressed, such as depression or anxiety. Failing to treat these concerns can make it more difficult to explore your gender identity and ease gender dysphoria.

Changes in gender expression and role

This might involve living part time or full time in another gender role that is consistent with your gender identity.

Medical treatment

Medical treatment of gender dysphoria might include:

• Hormone therapy, such as feminizing hormone therapy or masculinizing hormone therapy
• Surgery, such as feminizing surgery or masculinizing surgery to change the chest, external genitalia, internal genitalia, facial features and body contour

Some people use hormone therapy to seek maximum feminization or masculinization. Others might find relief from gender dysphoria by using hormones to minimize secondary sex characteristics, such as breasts and facial hair.

Treatments are based on your goals and an evaluation of the risks and benefits of medication use. Treatments may also be based on the presence of any other conditions and consideration of your social and economic issues. Many people also find that surgery is necessary to relieve their gender dysphoria.

The World Professional Association for Transgender Health provides the following criteria for hormonal and surgical treatment of gender dysphoria:

• Persistent, well-documented gender dysphoria.
• Capacity to make a fully informed decision and consent to treatment.
• Legal age in a person's country or, if younger, following the standard of care for children and adolescents.
• If significant medical or mental concerns are present, they must be reasonably well controlled.

Additional criteria apply to some surgical procedures.

A pre-treatment medical evaluation is done by a doctor with experience and expertise in transgender care before hormonal and surgical treatment of gender dysphoria. This can help rule out or address medical conditions that might affect these treatments This evaluation may include:

• A personal and family medical history
• A physical exam
• Assessment of the need for age- and sex-appropriate screenings
• Identification and management of tobacco use and drug and alcohol misuse
• Testing for HIV and other sexually transmitted infections, along with treatment, if necessary
• Assessment of desire for fertility preservation and referral as needed for sperm, egg, embryo or ovarian tissue cryopreservation
• Documentation of history of potentially harmful treatment approaches, such as unprescribed hormone use, industrial-strength silicone injections or self-surgeries

Behavioral health treatment

This treatment aims to improve your psychological well-being, quality of life and self-fulfillment. Behavioral therapy isn't intended to alter your gender identity. Instead, therapy can help you explore gender concerns and find ways to lessen gender dysphoria.

The goal of behavioral health treatment is to help you feel comfortable with how you express your gender identity, enabling success in relationships, education and work. Therapy can also address any other mental health concerns.

Therapy might include individual, couples, family and group counseling to help you:

• Explore and integrate your gender identity
• Accept yourself
• Address the mental and emotional impacts of the stress that results from experiencing prejudice and discrimination because of your gender identity (minority stress)
• Build a support network
• Develop a plan to address social and legal issues related to your transition and coming out to loved ones, friends, colleagues and other close contacts
• Become comfortable expressing your gender identity
• Explore healthy sexuality in the context of gender transition
• Make decisions about your medical treatment options
• Increase your well-being and quality of life

Therapy might be helpful during many stages of your life.

A behavioral health evaluation may not be required before receiving hormonal and surgical treatment of gender dysphoria, but it can play an important role when making decisions about treatment options. This evaluation might assess:

• Gender identity and dysphoria
• Impact of gender identity in work, school, home and social environments, including issues related to discrimination, abuse and minority stress
• Mood or other mental health concerns
• Risk-taking behaviors and self-harm
• Substance misuse
• Sexual health concerns
• Social support from family, friends and peers — a protective factor against developing depression, suicidal thoughts, suicide attempts, anxiety or high-risk behaviors
• Goals, risks and expectations of treatment and trajectory of care

Other steps

Other ways to ease gender dysphoria might include use of:

• Peer support groups
• Voice and communication therapy to develop vocal characteristics matching your experienced or expressed gender
• Hair removal or transplantation
• Genital tucking
• Breast binding
• Breast padding
• Aesthetic services, such as makeup application or wardrobe consultation
• Legal services, such as advanced directives, living wills or legal documentation
• Social and community services to deal with workplace issues, minority stress or parenting issues

More Information

Gender dysphoria care at Mayo Clinic

• Pubertal blockers
• Feminizing hormone therapy
• Feminizing surgery
• Gender-affirming (transgender) voice therapy and surgery
• Masculinizing hormone therapy
• Masculinizing surgery

Clinical trials

Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this condition.

Coping and support

Gender dysphoria can be lessened by supportive environments and knowledge about treatment to reduce the difference between your inner gender identity and sex assigned at birth.

Social support from family, friends and peers can be a protective factor against developing depression, suicidal thoughts, suicide attempts, anxiety or high-risk behaviors.

Other options for support include:

• Mental health care. You might see a mental health professional to explore your gender, talk about relationship issues, or talk about any anxiety or depression you're experiencing.
• Support groups. Talking to other transgender or gender-diverse people can help you feel less alone. Some community or LGBTQ centers have support groups. Or you might look online.
• Prioritizing self-care. Get plenty of sleep. Eat well and exercise. Make time to relax and do the activities you enjoy.
• Meditation or prayer. You might find comfort and support in your spirituality or faith communities.
• Getting involved. Give back to your community by volunteering, including at LGBTQ organizations.

Preparing for your appointment

You may start by seeing your primary care provider. Or you may be referred to a behavioral health professional.

Here's some information to help you get ready for your appointment.

What you can do

Before your appointment, make a list of:

• Your symptoms , including any that seem unrelated to the reason for your appointment
• Key personal information , including major stresses, recent life changes and family medical history
• All medications, vitamins or other supplements you take, including the doses
• Questions to ask your health care provider
• Ferrando CA. Comprehensive Care of the Transgender Patient. Elsevier; 2020. https://www.clinicalkey.com. Accessed Nov. 8, 2021.
• Hana T, et al. Transgender health in medical education. Bulletin of the World Health Organization. 2021; doi:10.2471/BLT.19.249086.
• Kliegman RM, et al. Gender and sexual identity. In: Nelson Textbook of Pediatrics. 21st ed. Elsevier; 2020. https://www.clinicalkey.com. Accessed Nov. 8, 2021.
• Ferri FF. Transgender and gender diverse patients, primary care. In: Ferri's Clinical Advisor 2022. Elsevier; 2022. https://www.clinicalkey.com. Accessed Nov. 8, 2021.
• Gender dysphoria. In: Diagnostic and Statistical Manual of Mental Disorders DSM-5. 5th ed. American Psychiatric Association; 2013. https://dsm.psychiatryonline.org. Accessed Nov. 8, 2021.
• Keuroghlian AS, et al., eds. Nonmedical, nonsurgical gender affirmation. In: Transgender and Gender Diverse Health Care: The Fenway Guide. McGraw Hill; 2022. https://accessmedicine.mhmedical.com. Accessed Nov. 8, 2021.
• Coleman E, et al. Surgery. In: Standards of Care for the Health of Transsexual, Transgender and Gender Nonconforming People. Version 7. World Professional Association for Transgender Health; 2012. https://www.wpath.org/publications/soc. Accessed Nov. 3, 2021.

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Practical Guidelines for Transgender Hormone Treatment

Adapted from:  Gardner,   Ivy  and  Safer, Joshua D . 2013   Progress on the road to better medical care for transgender patients. Current Opinion in Endocrinology, Diabetes and Obesity 20(6): 553-558.

• In order to improve transgender individuals’ access to health care, the approach to transgender medicine needs to be generalized and accessible to physicians in multiple specialties.
• A practical target for hormone therapy for transgender men (FTM) is to increase testosterone levels to the normal male physiological range (300–1000 ng/dl) by administering testosterone.
• A practical target for hormone therapy for transgender women (MTF) is to decrease testosterone levels to the normal female range (30–100 ng/dl) without supra- physiological levels of estradiol (<200 pg/ml) by administering an antiandrogen and estrogen.
• Transgender adolescents usually have stable gender identities and can be given GnRH analogs to suppress puberty until they can proceed with hormone therapy as early as age 16.

Hormone regimes for transgender men (female to men, FTM)

    1. Oral

• Testosterone undecanoate*      160–240mg/day

   2. Parenterally (i.m. or subcutaneous)

• Testosterone enanthate or cypionate      50–200mg/week or 100–200mg/2 weeks
• Testosterone undecanoate      1000 mg/12 weeks

   3. Transdermal

• Testosterone 1% gel      2.5 – 10 g/day
• Testosterone patch      2.5 – 7.5 mg/day 

i.m., intramuscular. *Not available in the USA.

Monitoring for transgender men (FTM) on hormone therapy:

• Monitor for virilizing and adverse effects every 3 months for first year and then every 6 – 12 months.
• Monitor serum testosterone at follow-up visits with a practical target in the male range (300 – 1000 ng/dl). Peak levels for patients taking parenteral testosterone can be measured 24 – 48 h after injection. Trough levels can be measured immediately before injection.
• Monitor hematocrit and lipid profile before starting hormones and at follow-up visits.
• Bone mineral density (BMD) screening before starting hormones for patients at risk for osteo- porosis. Otherwise, screening can start at age 60 or earlier if sex hormone levels are consistently low.
• FTM patients with cervixes or breasts should be screened appropriately.

Hormone regimes for transgender women (male to women, MTF)  

     1. Anti-androgen

• Spironolactone    100 – 200 mg/day (up to 400 mg)
• Cyproterone acetatea    50–100mg/day
• GnRH agonists    3.75 mg subcutaneous monthly

    2. Oral estrogen

• Oral conjugated estrogens    2.5–7.5mg/day
• Oral 17-beta estradiol    2–6mg/day

    3. Parenteral estrogen

• Estradiol valerate   5–20mg i.m./2 weeks   or cypionate   2–10mg i.m./week

    4. Transdermal estrogen

• Estradiol patch     0.1–0.4mg/2X week

i.m., Intramuscular; MTF, male to female. aNot available in the USA.

Monitoring for transgender women (MTF) on hormone therapy:

• Monitor for feminizing and adverse effects every 3 months for first year and then every 6– 12 months.
• Monitor serum testosterone and estradiol at follow-up visits with a practical target in the female range (testosterone 30 – 100 ng/dl; E2 <200 pg/ml).
• Monitor prolactin and triglycerides before start- ing hormones and at follow-up visits.
• Monitor potassium levels if the patient is taking spironolactone.
• BMD screening before starting hormones for patients at risk for osteoporosis. Otherwise, start screening at age 60 or earlier if sex hormone levels are consistently low.
• MTF patients should be screened for breast and prostate cancer appropriately.

3. Leinung MC, Urizar MF, Patel N, Sood SC. Endocrine treatment of transsexual  * persons: extensive personal experience. Endocr Pract 2013; 19:644 – 650.

4. Gorin-Lazard A, Baumstarck K, Boyer L, et al. Is hormonal therapy associated *with better quality of life in transsexuals? A cross-sectional study. J Sex Med 2012; 9:531–541.

5. Obedin-Maliver J, Goldsmith ES, Stewart L, et al. Lesbian, gay, bisexual, and transgender-related content in undergraduate medical education. J Am Med Assoc 2011; 306:971 – 977.

6. Safer JD, Tangpricha V. Out of the shadows: it is time to mainstream treatment for transgender patients. Endocrine Pract 2008; 14:248 – 250.

7. Reiner WG, Gearhart JP. Discordant sexual identity in some genetic males with cloacal exstrophy assigned to female sex at birth. N Engl J Med 2004; 350:333 – 341.

8. Meyer-Bahlburg HFL. Gender identity outcome in female-raised 46,XY per- sons with penile agenesis, cloacal exstrophy of the bladder, or penile ablation. Arch Sex Behav 2005; 34:423 – 438.

9. Zhou J-N, Hofman MA, Gooren LJG, Swaab DF. A sex difference in the human brain and its relation to transsexuality. Nature 1995; 378:68 – 70.

10. Kruijver FP, Zhou JN, Pool CW, et al. Male-to-female transsexuals have female neuron numbers in a limbic nucleus. J Clin Endocrinol Metab 2000; 85:2034 – 204z

11. Berglund H, Lindstro ̈ m P, Dhejne-Helmy C, Savic I. Male-to-female transsex- uals show sex-atypical hypothalamus activation when smelling odorous steroids. Cerebr Cortex 2008; 18:1900 – 1908.

12. Rametti G, Carrillo B, Go ́mez-Gil E, et al. White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study. J Psychiatr Res 2011; 45:199 – 204.

13. RamettiG,CarrilloB,Go ́mez-GilE,etal.Themicrostructureofwhitematterin male to female transsexuals before cross-sex hormonal treatment. A DTI study. J Psychiatr Res 2011; 45:949–954.

14. GreenR,NewmanL,StollerR.Treatmentofboyhood‘transsexualism’.Arch Gen Psychiatry 1972; 26:213–217.

15. Liao L-M, Audi L, Magritte E, et al. Determinant factors of gender identity: a commentary. J Pediatr Urol 2012; 8:597–601.

16. World Professional Association for Transgender Health. Standards of care for the health of transsexual, transgender, and gender nonconforming people. 7th ed.; 2011. http://www.wpath.org/documents/Standards%20of%20Care% 20V7%20-%202011%20WPATH.pdf (Accessed on 24 December 2012)

17. Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, et al. Endo- crine treatment of transsexual persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2009; 94:3132 – 3154.

18. Gooren LJ. Care of transsexual persons. N Engl J Med 2011; 364:2559– 2560.

19. BhasinS,SaferJ,TangprichaV.Thehormonefoundation’spatientguideto the endocrine treatment of transsexual persons. J Clin Endocrinol Metab 2009; 94:.

20. Bockting WO, Miner MH, Swinburne Romine RE, et al. Stigma, mental health, *  and resilience in an online sample of the US transgender population. Am J Public Health 2013; 103:943 – 951.

21. Olshan JS, Spack NP, Eimicke T, et al. Evaluation of the efficacy of sub-cutaneous administration of testosterone in female to male transexuals and hypogonadal males. Endocr Rev 2013; 34:(03_MeetingAbstracts): MON- 594.

22. Nagarajan V, Chamsi-Pasha M, Tang WHW. The role of aldosterone receptor antagonists in the management of heart failure: an update. Cleve Clin J Med 2012; 79:631 – 639.

23. Asscheman H, Giltay EJ, Megens JAJ, et al. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol 2011; 164:635 – 642.

24. Wierckx K, Mueller S, Weyers S, et al. Long-term evaluation of cross-sex * hormone treatment in transsexual persons. J Sex Med 2012; 9:2641–2651.

25. Wallien MSC, Cohen-Kettenis PT. Psychosexual outcome of gender-dysphoric children. J Am Acad Child Adolesc Psychiatry 2008; 47:1413 – 1423. 26. Cohen-Kettenis PT, Delemarre-van de Waal HA, Gooren LJG. The treatment of adolescent transsexuals: changing insights. J Sex Med 2008; 5:1892–1897.

27. De Vries ALC, Steensma TD, Doreleijers TAH, Cohen-Kettenis PT. Puberty suppression in adolescents with gender identity disorder: a prospective follow-up study. J Sex Med 2011; 8:2276 – 2283.

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Treatment - Gender dysphoria

Treatment for gender dysphoria aims to help people live the way they want to, in their preferred gender identity or as non-binary.

What this means will vary from person to person, and is different for children, young people and adults. Waiting times for referral and treatment are currently long.

Treatment for children and young people

If your child may have gender dysphoria, they'll usually be referred to one of the NHS Children and Young People's Gender Services .

Your child or teenager will be seen by a multidisciplinary team including a:

• clinical psychologist
• child psychotherapist
• child and adolescent psychiatrist
• family therapist
• social worker

The team will carry out a detailed assessment, usually over 3 to 6 appointments over a period of several months.

Depending on the results of the assessment, options for children and teenagers include:

• family therapy
• individual child psychotherapy
• parental support or counselling
• group work for young people and their parents
• regular reviews to monitor gender identity development
• referral to a local Children and Young People's Mental Health Service (CYPMHS) for more serious emotional issues

Most treatments offered at this stage are psychological rather than medical. This is because in many cases gender variant behaviour or feelings disappear as children reach puberty.

Hormone therapy in children and young people

Some young people with lasting signs of gender dysphoria who meet strict criteria may be referred to a hormone specialist (consultant endocrinologist). This is in addition to psychological support.

Puberty blockers and gender-affirming hormones

Puberty blockers (gonadotrophin-releasing hormone analogues) are not available to children and young people for gender incongruence or gender dysphoria because there is not enough evidence of safety and clinical effectiveness.

From around the age of 16, young people with a diagnosis of gender incongruence or gender dysphoria who meet various clinical criteria may be given gender-affirming hormones alongside psychosocial and psychological support.

These hormones cause some irreversible changes, such as:

• breast development (caused by taking oestrogen)
• breaking or deepening of the voice (caused by taking testosterone)

Long-term gender-affirming hormone treatment may cause temporary or even permanent infertility.

However, as gender-affirming hormones affect people differently, they should not be considered a reliable form of contraception.

There is some uncertainty about the risks of long-term gender-affirming hormone treatment.

Children, young people and their families are strongly discouraged from getting puberty blockers or gender-affirming hormones from unregulated sources or online providers that are not regulated by UK regulatory bodies.

Transition to adult gender identity services

Young people aged 17 or older may be seen in an adult gender identity clinic or be referred to one from a children and young people's gender service.

By this age, a teenager and the clinic team may be more confident about confirming a diagnosis of gender dysphoria. If desired, steps can be taken to more permanent treatments that fit with the chosen gender identity or as non-binary.

Treatment for adults

Adults who think they may have gender dysphoria should be referred to a gender dysphoria clinic (GDC).

Find an NHS gender dysphoria clinic in England .

GDCs have a multidisciplinary team of healthcare professionals, who offer ongoing assessments, treatments, support and advice, including:

• psychological support, such as counselling
• cross-sex hormone therapy
• speech and language therapy (voice therapy) to help you sound more typical of your gender identity

For some people, support and advice from the clinic are all they need to feel comfortable with their gender identity. Others will need more extensive treatment.

Hormone therapy for adults

The aim of hormone therapy is to make you more comfortable with yourself, both in terms of physical appearance and how you feel. The hormones usually need to be taken for the rest of your life, even if you have gender surgery.

It's important to remember that hormone therapy is only one of the treatments for gender dysphoria. Others include voice therapy and psychological support. The decision to have hormone therapy will be taken after a discussion between you and your clinic team.

In general, people wanting masculinisation usually take testosterone and people after feminisation usually take oestrogen.

Both usually have the additional effect of suppressing the release of "unwanted" hormones from the testes or ovaries.

Whatever hormone therapy is used, it can take several months for hormone therapy to be effective, which can be frustrating.

It's also important to remember what it cannot change, such as your height or how wide or narrow your shoulders are.

The effectiveness of hormone therapy is also limited by factors unique to the individual (such as genetic factors) that cannot be overcome simply by adjusting the dose.

Find out how to save money on prescriptions for hormone therapy medicines with a prescription prepayment certificate .

Risks of hormone therapy

There is some uncertainty about the risks of long-term cross-sex hormone treatment. The clinic will discuss these with you and the importance of regular monitoring blood tests with your GP.

The most common risks or side effects include:

• blood clots
• weight gain
• dyslipidaemia (abnormal levels of fat in the blood)
• elevated liver enzymes
• polycythaemia (high concentration of red blood cells)
• hair loss or balding (androgenic alopecia)

There are other risks if you're taking hormones bought over the internet or from unregulated sources. It's strongly recommended you avoid these.

Long-term cross-sex hormone treatment may also lead, eventually, to infertility, even if treatment is stopped.

The GP can help you with advice about gamete storage. This is the harvesting and storing of eggs or sperm for your future use.

Gamete storage is sometimes available on the NHS. It cannot be provided by the gender dysphoria clinic.

Read more about fertility preservation on the HFEA website.

Surgery for adults

Some people may decide to have surgery to permanently alter body parts associated with their biological sex.

Based on the recommendations of doctors at the gender dysphoria clinic, you will be referred to a surgeon outside the clinic who is an expert in this type of surgery.

In addition to you having socially transitioned to your preferred gender identity for at least a year before a referral is made for gender surgery, it is also advisable to:

• lose weight if you are overweight (BMI of 25 or over)
• have taken cross-sex hormones for some surgical procedures

It's also important that any long-term conditions, such as diabetes or high blood pressure, are well controlled.

Surgery for trans men

Common chest procedures for trans men (trans-masculine people) include:

• removal of both breasts (bilateral mastectomy) and associated chest reconstruction
• nipple repositioning
• dermal implant and tattoo

Gender surgery for trans men includes:

• construction of a penis (phalloplasty or metoidioplasty)
• construction of a scrotum (scrotoplasty) and testicular implants
• a penile implant

Removal of the womb (hysterectomy) and the ovaries and fallopian tubes (salpingo-oophorectomy) may also be considered.

Surgery for trans women

Gender surgery for trans women includes:

• removal of the testes (orchidectomy)
• removal of the penis (penectomy)
• construction of a vagina (vaginoplasty)
• construction of a vulva (vulvoplasty)
• construction of a clitoris (clitoroplasty)

Breast implants for trans women (trans-feminine people) are not routinely available on the NHS.

Facial feminisation surgery and hair transplants are not routinely available on the NHS.

As with all surgical procedures there can be complications. Your surgeon should discuss the risks and limitations of surgery with you before you consent to the procedure.

Life after transition

Whether you've had hormone therapy alone or combined with surgery, the aim is that you no longer have gender dysphoria and feel at ease with your identity.

Your health needs are the same as anyone else's with a few exceptions:

• you'll need lifelong monitoring of your hormone levels by your GP
• you'll still need contraception if you are sexually active and have not yet had any gender surgery
• you'll need to let your optician and dentist know if you're on hormone therapy as this may affect your treatment
• you may not be called for screening tests as you've changed your name on medical records – ask your GP to notify you for cervical and breast screening if you're a trans man with a cervix or breast tissue
• trans-feminine people with breast tissue (and registered with a GP as female) are routinely invited for breast screening from the ages of 50 up to 71

Find out more about screening for trans and non-binary people on GOV.UK.

NHS guidelines for gender dysphoria

NHS England has published what are known as service specifications that describe how clinical and medical care is offered to people with gender dysphoria:

• Non-surgical interventions for adults
• Surgical interventions for adults
• Interim service specification for specialist gender incongruence services for children and young people

Review of gender identity services

NHS England has commissioned an independent review of gender identity services for children and young people. The review will advise on any changes needed to the service specifications for children and young people.

Page last reviewed: 28 May 2020 Next review due: 28 May 2023

Hormonal Gender Reassignment Treatment for Gender Dysphoria

Affiliation.

• 1 Medical Clinic I: Gastroenterology and Hepatology, Pneumology and Allergology, Endocrinology and Diabetology, Nutritional Medicine, University Hospital Frankfurt, Frankfurt, Germany.
• PMID: 33559593
• PMCID: PMC7871443
• DOI: 10.3238/arztebl.2020.0725

Background: No data are available at present on the prevalence of gender dysphoria (trans-identity) in Germany. On the basis of estimates from the Netherlands, it can be calculated that approximately 15 000 to 25 000 persons in Germany are affected. Persons suffering from gender dysphoria often experience significant distress and have a strong desire for gender reassignment treatment.

Methods: This review is based on pertinent publications retrieved by a selective search in the PubMed database employing the searching terms "transsexualism," "transgender," "gender incongruence," "gender identity disorder," "gender-affirming hormone therapy," and "gender dysphoria."

Results: In view of its far-reaching consequences, some of which are irreversible, hormonal gender reassignment treatment should only be initiated after meticulous individual consideration, with the approval of the treating psychiatrist/psychotherapist and after extensive information of the patient by an experienced endo - crinologist. Before the treatment is begun, the patient must be extensively screened for risk factors. The contraindications include severe preexisting thromboembolic diseases (mainly if untreated), hormone-sensitive tumors, and uncontrolled pre - existing chronic diseases such as arterial hypertension and epilepsy. Finding an appropriate individual solution is the main objective even if contraindications are present. Male-to-female treatment is carried out with 17β-estradiol or 17β-estradiol valerate in combination with cyproterone acetate or spironolactone as an antiandrogen, female-to-male treatment with transdermal or intramuscular testosterone preparations. The treatment must be monitored permanently with clinical and laboratory follow-up as well as with gynecological and urological early-detection screening studies. Prospective studies and a meta-analysis (based on low-level evidence) have documented an improvement in the quality of life after gender reassignment treatment. Female-to-male gender-incongruent persons often have difficulty being accepted in a gynecological practice as a male patient.

Concluzion: Further prospective studies for the quantification of the risks and benefits of hormonal treatment would be desirable. Potential interactions of the hormone preparations with other medications must always be considered.

Publication types

• Meta-Analysis
• Gender Dysphoria* / drug therapy
• Germany / epidemiology
• Prospective Studies
• Quality of Life
• Sex Reassignment Surgery*
• Transgender Persons*
• Transsexualism*

Medications for Gender Dysphoria

Other names: Gender Identity Disorder; GID; Transsexualism

Gender dysphoria is when your emotional and psychological identity as male or female conflicts with your birth-assigned gender.

Drugs used to treat Gender Dysphoria

The medications listed below are related to or used in the treatment of this condition.

Learn more about Gender Dysphoria

Medicine.com guides (external).

• Gender Dysphoria Guide

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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Testosterone therapy: Study suggests it's a safe and effective gender-affirming hormone therapy for trans men

by Okayama University

Transgender individuals often face unique challenges in aligning their physical bodies with their true gender identity. Among the various methods employed, gender-affirming hormone therapy (GAHT) stands as a vital means for transgender men to achieve physical changes in consonance with their gender identity.

Navigating the complexities that come with gender transition, transgender individuals seek medical interventions to alleviate gender dysphoria and align their bodies with their gender identity.

For transgender men , testosterone therapy holds promise in inducing masculinizing effects such as increased muscle mass , cessation of menstruation, and deepening of the voice. However, the lack of comprehensive research on the long-term effects and safety of testosterone therapy poses significant challenges in clinical decision-making and underscores the persistent taboo surrounding transgender health care.

To address this pressing need, a study led by Assistant Professor Yusuke Tominaga along with Dr. Tomoko Kobayashi and Dr. Motoo Araki from the Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan dives into understanding the long-term physical effects and safety profile of testosterone therapy for transgender men, shedding light on crucial aspects of hormone administration and its impact on body composition.

Their research findings were published in Andrology on 2 April 2024.

"The research team was inspired to investigate this area as we noticed the lack of a standardized regimen for testosterone dosage and administration. Our aim was to understand how hormone dosages are adjusted to align more closely with typical male testosterone levels in the bloodstream," explains Dr. Tominaga.

Analyzing data from transgender men who commenced GAHT between May 2000 and December 2021, the researchers meticulously recorded physical findings, blood test results, and menstrual cessation rates. They then compared the effects of testosterone on body composition changes and laboratory parameters, stratifying participants into low-dose and high-dose groups based on their testosterone dosage.

The findings of the study revealed that both low-dose and high-dose testosterone regimens demonstrated favorable outcomes, with no significant differences observed in menstrual cessation rates up to 12 months. Over time, participants exhibited a decrease in body fat percentage and an increase in lean body mass , indicative of the desired masculinizing effects of testosterone therapy.

Notably, the high-dose group exhibited greater gains in lean body mass during the initial year of therapy, suggesting a potential strategy for individuals seeking more rapid changes in body composition. Importantly, the study found no evidence of long-term, dose-dependent side effects such as polycythemia or dyslipidemia, reassuring both clinicians and transgender individuals regarding the safety profile of testosterone therapy.

Reflecting on the significance of their findings, Dr. Tominaga explains, "Our study contributes valuable evidence on the long-term effects of testosterone therapy, providing crucial insights for clinicians managing transgender health care. By elucidating the safety and efficacy of hormone therapy, we hope to alleviate uncertainties surrounding transgender health care and empower individuals to make informed decisions about their treatment."

This study opens the door to more inclusive and evidence-based care by illuminating the long-term effects and safety of testosterone therapy for transgender men.

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A.G. File No. 2023-020

Pursuant to Elections Code Section 9005, we have reviewed the proposed measure (A.G. File No. 23-0020, Amendment #1) related to certain gender-affirming medical procedures for individuals under the age of 18 years.

Some Children Are Transgender. Sex generally refers to a person being biologically male, female, or intersex. The attitudes, feelings, and behaviors that a given culture associates with these biological designations are generally known as gender. Gender identity generally refers to an individual’s internal sense of being male, female, or something else. For example, transgender individuals have gender identities that differ from the sex assigned to them at birth.

Transgender Children Are a Small Share of California’s Population. Data on transgender individuals are limited. That said, research suggests that transgender individuals comprise a small share of children. For example, one recent study by the Williams Institute at the University of California, Los Angeles estimates that nearly 50,000 individuals (around 2 percent) of individuals between the age of 13 to 17 years identify as transgender in California.

Some Transgender Children Receive Health Care Services to Affirm Their Gender Identity. Some transgender individuals experience distress from having a gender identity that is different from their sex assigned to them at birth. Transgender individuals experiencing distress can receive certain health care services, including mental health services and medical treatments. These treatments can be a part of what is referred to as “gender affirming care.” Medical treatments can include prescription drugs to postpone the development of puberty (known as “puberty blockers”), hormone therapies, and surgeries. For transgender children, decisions around which treatment to provide and when to provide the treatment are made jointly by the physician and parent of the child, generally following professionally recognized standards.

California Law Protects Access to Gender-Affirming Care. A number of laws in California protect access to gender-affirming care for transgender individuals. For example, California law prohibits health insurance plans from discriminating against transgender patients, including by denying patients access to gender-affirming treatments when the treatments are medically necessary.

California Helps Pay for Health Care for Many Individuals, Including Gender Affirming Care. State and local governments help certain Californians pay for health care through a number of different programs. For example, Medicaid, known as “Medi-Cal” in California, provides health coverage to eligible low-income California residents. It is funded from a mix of federal, state, and local funds. Health care services covered by Medi-Cal include gender affirming care for transgender individuals, generally when considered to be medically necessary.

California Licenses Health Care Providers. California law requires health insurance plans, health care providers, and health care facilities to be licensed to provide health care services. Several departments are responsible for licensing health care entities in California. For example, the Department of Consumer Affairs includes numerous licensing boards that license health care providers, such as physicians, nurses, and pharmacists, among others. These departments and boards generally cover the cost to license providers and investigate complaints by charging affected providers fees and fines.

Prohibits Providing Certain Medical Treatments That Affirm a Different Gender Than Biological Sex for Youth. The measure would prohibit health care providers (such as a physician or a nurse) from providing patients under the age of 18 certain medical treatments that affirm a gender identity different than the patient’s biological sex. The initiative specifically would prohibit prescribing or administering puberty blockers, hormones or hormone antagonists, and surgery or medical procedures. The measure defines biological sex as either male or female, based on specified physiological and genetic attributes.

Excludes Three Kinds of Services From Prohibitions. The measure would exclude from these prohibitions the following: (1) services medically necessary to treat a minor born with a medically verifiable genetic disorder of sexual development; (2) services to return a child who previously received gender-affirming procedures back to his or her biological sex; and (3) services to children who began gender-affirming procedures prior to when the measure becomes law or January 1, 2025, whichever is earlier.

Enacts Consequences to Providers for Providing Services. Except for the exclusions described in the previous paragraph, providing a prohibited medical service under the measure would be considered unprofessional conduct and subject to discipline and a hearing process by the provider’s licensing entity. The measure specifies that such discipline would include revoking of the health care provider’s license or certification.

Fiscal Effect

Impact Depends on Court Rulings Related to Gender-Affirming Health Care. In recent years, several states have enacted prohibitions on health care providers from providing certain gender-affirming medical treatments, including treatments that would be prohibited under this measure. Many of these laws are being litigated in the federal court system to determine whether they conflict with the United States Constitution. At the time of this analysis, the courts have allowed bans in some states to take effect, while bans in other states have not been allowed to go into effect. If a court were to rule this measure could not go into effect, it would have no fiscal effect. Alternatively, were the measure to withstand legal challenges, there would be fiscal effects, described below.

If Measure Becomes Law, Possible Minor Savings From No Longer Covering Prohibited Treatments… Were the measure to become law, state and local government health programs that pay for gender-affirming puberty blockers, hormone therapies, and surgeries for youth could no longer do so. Although comprehensive data on state and local government spending for these services is not available, it could be as much as in the millions of dollars annually. This represents a very small share of overall state and local spending, with the state General Fund providing $37.5 billion to Medi-Cal in 2023-24, for example.

…Could Be Impacted by Other Long-Term Effects. The savings from no longer paying for health care services could be increased, reduced, or even offset by other health-related impacts. For example, some Medi-Cal enrollees under the age of 18 who otherwise would have received prohibited services may choose to receive some of these services when they are adults. In these cases, some of the spending associated with prohibited services would still occur, but at a later time for the individual. In other cases, individuals who are eligible for Medi-Cal as children may earn too much income to qualify for Medi-Cal as adults or forgo these services altogether. These effects are difficult to project. Also adding to the fiscal uncertainty, the long-term effects on mental and physical health of providing gender-affirming care to transgender youth are actively being studied. Depending on these long-term impacts, prohibiting certain gender-affirming medical treatments on individuals under the age of 18 could affect the use of health care services, with corresponding fiscal impacts

Potential, but Unknown, Cost Pressure Related to Federal Anti-Discrimination Laws. Federal law prohibits health care providers that receive federal funding for health programs (such as Medicaid) from discriminating against patients on the basis of race, sex, and other factors. Federal courts currently are assessing whether these nondiscrimination provisions extend to gender identity and the provision of gender-affirming care. Depending on the decisions in these court cases and any resulting federal actions, California providers could face a number of potential consequences, including revoked federal funding. Such actions also could place pressure on state and local governments to backfill lost federal funding. Whether action is taken and the magnitude of such action is unknown, but the impact could be significant.

Summary of Fiscal Effects. We estimate the measure would have the following fiscal effects:

• To the extent the measure can be legally implemented, potentially relatively minor savings up to the millions of dollars annually from no longer paying for prohibited services for individuals under the age of 18. These savings could be affected by many other impacts, such as individuals seeking treatment later in life.
• Potential, but unknown, cost pressure to state and local governments related to federal fiscal penalties if the measure results in providers being deemed out of compliance with federal law.

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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

Rafael delgado-ruiz.

1 Prosthodontics and Digital Technology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USA; [email protected]

Patricia Swanson

Georgios romanos.

2 Periodontology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USA; [email protected]

This study seeks to evaluate the long-term effects of pharmacologic therapy on the bone markers and bone mineral density of transgender patients and to provide a basis for understanding its potential implications on therapies involving implant procedures. Following the referred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and well-defined PICOT (Problem/Patient/Population, Intervention, Comparison, Outcome, Time) questionnaires, a literature search was completed for articles in English language, with more than a 3 year follow-up reporting the long-term effects of the cross-sex pharmacotherapy on the bones of adult transgender patients. Transgender demographics, time under treatment, and treatment received were recorded. In addition, bone marker levels (calcium, phosphate, alkaline phosphatase, and osteocalcin), bone mineral density (BMD), and bone turnover markers (Serum Procollagen type I N-Terminal pro-peptide (PINP), and Serum Collagen type I crosslinked C-telopeptide (CTX)) before and after the treatment were also recorded. The considerable variability between studies did not allow a meta-analysis. All the studies were completed in European countries. Transwomen (921 men to female) were more frequent than transmen (719 female to male). Transwomen’s treatments were based in antiandrogens, estrogens, new drugs, and sex reassignment surgery, meanwhile transmen’s surgeries were based in the administration of several forms of testosterone and sex reassignment. Calcium, phosphate, alkaline phosphatase, and osteocalcin levels remained stable. PINP increased in transwomen and transmen meanwhile, CTX showed contradictory values in transwomen and transmen. Finally, reduced BMD was observed in transwomen patients receiving long-term cross-sex pharmacotherapy. Considering the limitations of this systematic review, it was concluded that long-term cross-sex pharmacotherapy for transwomen and transmen transgender patients does not alter the calcium, phosphate, alkaline phosphatase, and osteocalcin levels, and will slightly increase the bone formation in both transwomen and transmen patients. Furthermore, long-term pharmacotherapy reduces the BMD in transwomen patients.

1. Introduction

The term “transgender” describes a population experiencing incongruence between their physical sex characteristics (assigned gender) and their gender identity (the extent to which people experience themselves to be like others of one gender) [ 1 ]. In some instances, as a result of the incongruence between assigned gender and gender identity, an individual can suffer distress (gender dysphoria), which may be accompanied by physical or mental health issues [ 2 ].

Patients experiencing gender dysphoria present with different requests; these patients include subjects requiring a transition to the opposite sex with the support of different medical specialists, those who aspire to live outside stereotypic roles without biological transformation, individuals who need medical care for health issues other than gender, and patients who require psychiatric support [ 3 ]. Those subjects who wish to transition to the opposite sex usually receive pharmacotherapy to increase their secondary sexual characteristics and may also undergo surgical procedures for gender reassignment [ 4 ].

The pharmacotherapy for sex transition is based on hormonal and non-hormonal treatments with the goal of partial or full inhibition of the patient’s gonadal axis and an increase in their secondary sex characteristics [ 5 , 6 ]. Male-to-female patients utilize hormonal estrogen preparations (different compounds of estradiol) and anti-androgens, such as spironolactone and gonadotropin-releasing hormone agonists (GnRH) [ 7 ]. Spironolactone decreases the response to androgens because it inhibits the androgen receptor, possesses a feminizing effect, reduces facial hair, and slows male alopecia. Furthermore, it provides additive effects to estrogen intake, allowing the estrogen dosage to be reduced (thus reducing the risks involved with higher doses of estrogen) [ 8 ]. On the other hand, GnRH agonists inhibit testosterone secretion by restraining luteinizing hormone secretion and thereby result in gonadal suppression [ 7 , 8 ].

Female-to-male patients utilize testosterone-based and non-testosterone-based therapy [ 9 ]. Non-testosterone therapies include medroxyprogesterone, GnRH agonists, 5-alpha reductase inhibitors, and selective serotonin receptor inhibitors (SSRIs) [ 10 ]. These therapies can support the offset of the side effects of testosterone therapy and support other aspects of the sex transition. For example, medroxyprogesterone assists with menstrual cessation, the GnRH agonists also reduce menses and refractory uterine bleedings, as well as the 5-alpha reductase inhibitors, and SSRI’s help with hair overgrowth or hair loss [ 9 , 10 , 11 ].

However, as a consequence of the pharmacological treatment received by the patients who have transitioned or are in the process of transitioning to the opposite sex, unintended systemic biological changes may occur. These may include an increased cardiovascular risk in both transwomen and transmen [ 4 ], a significant increase of body mass index and systolic and diastolic blood pressure in transmen [ 12 ], and osteoporosis at the lumbar spine and distal arm in transwoman [ 13 ]. Reported adverse effects also include venous thromboembolism, fractures, cardiovascular disease, stroke, and hormone-dependent cancers [ 14 ], and finally, with some disagreement, osteoporotic changes in the bone mass, density, and geometry in transmen and transwomen patients have been described [ 15 ].

Several investigations confirmed that testosterone and estrogens are essential to control bone health in men and women [ 16 , 17 , 18 ]. In men, testosterone plays a vital function for skeletal equilibrium, and estradiol is required for skeletal development [ 17 ]. In women, estrogens participate in bone homeostasis, but the effect of androgens is less clear [ 16 , 18 ]. This insinuates that bone metabolism might suffer variations as a result of transgender hormone therapy.

During hormone therapy, bone changes are evaluated periodically through bone mineral density (BMD), and bone turnover marker (BTM) analysis. BMD is estimated with Dual X-ray Absorptiometry (DEXA) and for the evaluation of active bone remodeling, BTMs are evaluated in serum and/or urine [ 19 ]. This allows for the prediction of the risk of osteoporosis, and the monitoring of treatment progression (effects of the therapy on bone metabolism and structure) [ 20 ].

The World Health Organization (WHO) standards consider that osteoporosis is present, when the T-score is <2.5 (standard deviation contrasted to the mean value of BMD of the specific population target) [ 21 ]. The BTMs for bone formation obtained from serum are: osteocalcin (OC), total alkaline phosphatase (ALP), bone-specific alkaline phosphatase (bone ALP), procollagen type I C-terminal pro-peptide (P1CP), and procollagen type I N-terminal pro-peptide (P1NP) [ 22 ].

Meanwhile, the BTMs for bone resorption can be obtained from serum (collagen type I cross-linked C-telopeptide (sCTX), carboxyterminal telopeptide of type I collagen (ICTP), tartrate-resistant acid phosphatase (TRACP), tartrate-resistant acid phosphatase 5b (s-TRACP 5b), and urine (collagen type I crosslinked N-telopeptide (uNTX)), collagen type I cross-linked C-telopeptide (uCTX), total pyridoline (uPYD), and total deoxypyridoline (uDPD) [ 23 ].

Nearly 0.6% of U.S. adults identify themselves as transgender [ 24 ], and global transgender prevalence has been reported in the United Kingdom (0.5%) [ 25 ], Belgium (0.6%) [ 26 ], and the Netherlands (0.9%) [ 27 ]. It has been reported that the transgender population encounters difficulties regarding access to health care [ 28 ] and that healthcare providers are not suitably prepared to adequately serve the transgender community [ 28 ].

Focusing on the oral care for transgender patients, the literature in the field is very scarce and mainly centered around dental fear [ 29 ] and dental education related to the topic [ 30 , 31 , 32 ], with only one clinical case published that related to full mouth rehabilitation of a transgender patient [ 33 ]. Unfortunately, there are no references to the bone parameters of the transgender population linked to oral and maxillofacial surgery or implant procedures, and, as Ludwig et al. (2018) stated, “We cannot provide evidence-based dental care to a subset of the population, if that population has yet to be studied.” [ 34 ].

Pharmacologic therapy may influence the bone structure of transgender patients receiving or rehabilitated with titanium implants or having oral and maxillofacial surgical procedures. Furthermore, the long-term effects of these therapies on bone mineral density, bone metabolism, and bone resorption are unknown.

Therefore, the goals of this systematic review were twofold:

• First, to answer the following PICOT (Problem/Patient/Population, Intervention, Comparison, Outcome, Time) question: In adult transgender patients (transwoman and transmen), receiving long-term pharmacologic therapy, are the bone markers and bone mineral density affected differently?
• Second, to provide a theoretical basis for a better understanding of the implications of the long-term pharmacologic therapy in the adult transgender patient on therapies involving orthopedic or dental implants.

2. Materials and Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed [ 35 ]. Electronic and manual searches were completed in Medline, EMBASE, and PubMed from January 2018 to December 2018 for the following search terms: “transgender AND bone health” OR “transgender AND cortical bone” OR “ transgender AND trabecular bone” OR “transgender AND bone structure” OR “transgender AND bone metabolism” OR “transgender AND bone mineral density” OR “transgender AND bone loss” OR “cross-sex hormone AND bone health” OR “pharmacotherapy AND transgender” OR “cross-sex AND cortical bone” OR “cross-sex AND trabecular bone” OR “cross-sex AND bone structure” OR “cross-sex AND bone metabolism” OR “cross-sex AND bone mineral density” OR “cross-sex AND bone loss” OR “cross-sex AND bone health”.

An additional manual search was completed within the references provided in the included manuscripts to identify other reports not returned by the electronic searches.

2.1. Study Inclusion Criteria

Long-term clinical studies completed in adult transgender populations (transwomen and transmen) that received pharmacological treatment were included as per the following inclusion criteria:

• Papers published in the English language from January 1990 through to December 2018;
• Publications reporting clinical studies with three or more years follow-up;
• Publications reporting the biological effects of cross-sex pharmacologic therapy in the bone markers, bone metabolism, and bone mineral density of transgender patients;
• Papers reporting the pharmacologic therapy used for transgender adults (including both retrospective and prospective studies).

If a study appeared duplicated, just the study that featured the most extensive follow-up, or the most recent study, was included.

2.2. Study Exclusion Criteria

• Articles published in languages other than English;
• Publications reporting less than three years of follow-up;
• Publications detailing the effects of cross-sex pharmacologic therapy in teenagers or young transgender patients;
• Publications reporting effects of cross-sex pharmacologic therapy not including the effects on bone
• Animal studies and in-vitro studies;
• Other systematic reviews and meta-analyses;
• Duplicated studies;
• Case reports.

Two reviewers (R.D. and G.R.) completed initial independent searches using the search terms. After the initial search, the titles and abstracts of the returned articles were read and articles that satisfied the inclusion criteria were selected. Afterward, the included articles were read in full and evaluated for final eligibility. The discrepancies between the reviewers were solved with the participation of a third, blinded reviewer (P.S.).

2.3. Data Extraction

The following information was extracted from all the included manuscripts:

• Transgender demographics: Number of males to female (transwomen) or female to male (transmen) patients included in each study;
• The duration of hormone-therapy treatment expressed in years or months;
• Type of hormone received by the patient and dosage.

2.3.1. Primary Outcomes

• Changes in bone metabolism marker levels calcium (mmol/L), phosphate (mmol/L), alkaline phosphatase (U/L), and osteocalcin (µg/L). Changes were measured at baseline and after treatment or at different time points for each of the bone metabolism markers.
• Changes in the BTMs including Serum Procollagen type I N-Terminal pro-peptide (PINP) (ng/mL) for evaluation of the bone formation, and Serum Collagen type I cross-linked C-telopeptide (CTX) (ng/mL) for evaluation of bone resorption. Changes were recorded at baseline and at different time points.
• Changes in the BMD. BMD values were registered at baseline and after the completion of treatment or at baseline and at different time points.

The obtained data were organized in tables ordered by year of publication from the oldest to the newest publication.

2.3.2. Risk of Bias

To determine the risk of bias in the included studies, the risk of bias assessment tool (RoB 2 tool) [ 36 ] was used. Five elements (domains) were assessed for each included manuscript including the randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result. Each domain was graded, and the risk of bias was scored as low risk of bias, some concerns, or high risk of bias, following the descriptors of the RoB 2 tool [ 36 ].

2.4. Statistical Analysis

Descriptive statistics, percentages, mean and standard deviations, and forest plot graphics were used for the presentation of the data. Meta-analysis was completed, if applicable, using a random effects model. Meta-analysis software (Comprehensive-Meta-analysis 3.0, Biostat, NJ, USA) was used for the statistical comparisons.

The initial search returned 564 articles. After reading the titles and abstracts, 471 articles were excluded. The remaining 93 articles were read in full and 84 articles were excluded (according to the exclusion criteria). Finally, nine manuscripts that fulfilled the inclusion criteria were included for this review ( Figure 1 ).

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) workflow. From the initial 586 articles, only nine articles fulfilled the inclusion criteria and were considered for this systematic review.

3.1. Transgender Demographics and Time under Treatment

Nine long-term studies featuring subjects who had undergone more than three years of pharmacotherapy treatment were included. Three studies were featured only male (M) to female (F) transgender patients, two studies were only included F to M transgender patients, and four studies featured both groups (M to F and F to M) [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. In addition to the pharmacotherapy, all the patients received sex reassignment surgery. The shortest period of evaluation was 3.5 years [ 40 ], and the longest was 18 years [ 45 ]. The total population studied was 1640 patients (921 M to F and 719 F to M transgender patients) ( Table 1 ).

Demographics, time receiving treatment, and medication received. Bone mineral density (BMD) and method of evaluation and study conclusions related to bone structure, bone metabolism, and bone mineral density. Variability was observed in drug dosages and regions for BMD. M, male; F, female.

3.2. Type of Hormone Received and Dosage

Different treatment modalities and different dosages were received by the patients. No comparison was possible between studies based on the used drugs. Variations between hormone type/dose/time as well as variations to the treatment due to adjustments by the provider and the individual patient’s characteristics precluded the comparisons.

• M to F

• Cyproterone + estrogens (high doses) [ 37 ].
• Ethinyl estradiol + cyproterone acetate and oral estrogens and estradiol valerate [ 38 ].
• Cyproterone acetate 2 mg/day + ethinyl estradiol 35–100 µg/day, after sex reassignment surgery estradiol valerate or 17-beta estradiol 2–4 mg/day [ 39 ].
• Cyproterone acetate 50–100 mg/day + ethinyl estradiol 25–50 μg/day, after surgery ethinyl estradiol 25–50 μg/day or estradiol valerate 2 mg/day or conjugated equine estrogens 1.25 mg/day.
• or transdermal estradiol [ 40 ].
• Cyproterone acetate 50–100 mg/day/1 year + exogenous estrogen, after surgery all received estrogens [ 41 ].
• Estrogens and anti-androgens until gonadectomy [ 42 ].

• F to M

Several forms of testosterone are administered

• Testosterone esters 250 mg/IM every 3 weeks, before and after surgery [ 38 ].
• Testosterone decanoate 100 mg, or testosterone isocaproate/fenylpropionate 60 mg, or testosterone propionate 30 mg/mL 2–3 weeks, or testosterone undecanoate 1000 mg 12 weeks, or transdermal testosterone 50 mg daily, or testosterone undecanoate 40 mg/day + testosterone gel 50 mg per 5 g, 50 mg daily [ 41 ].
• Testosterone [ 42 ].
• Different testosterone compounds [ 43 ].
• Testosterone isobutyrate, and after surgery, testosterone isobutyrate 25 mg intramuscular every week, or testosterone propionate 250 mg every 3 weeks intramuscular, or testosterone undecanoate 40 mg/4 times/day [ 45 ].

3.3. Bone Metabolism Marker Levels Before and After the Treatment

Calcium, phosphate, alkaline phosphatase, and osteocalcin were used in three of the studies. Data could not be compared due to the differences in population and methods of detection. In addition, the measuring units varied between mg/dL and mmol/L ( Table 2 ).

Bone metabolism markers were reported in three of the included studies. No differences were observed before and after long-term pharmacotherapy for transmen or transwomen.

M to F: A reduction of calcium of −0.244 (mg/dL), and reduction of phosphate of −0.188 (mg/dL) in the patients receiving hormone therapy compared to controls was observed by Sosa et al. 2003 [ 38 ]. No differences in calcium, phosphate, alkaline phosphatase, or osteocalcin in the patients receiving hormone therapy compared to controls by Ruetsche et al. 2005 [ 39 ]. F to M: No differences in calcium or phosphate were observed. Reduction in alkaline phosphatase from 36–120 (Ukat/L) in controls compared to 6.3 ± 1.5 (3.4–11.4) in tests. No changes in osteocalcin in the patients receiving hormone therapy compared to controls [ 39 ]. No changes were found in alkaline phosphatase and osteocalcin in patients receiving hormone therapy compared to male and female controls [ 45 ].

3.4. The Two Main Bone Turnover Markers

Both markers (PINP and CTX) were evaluated in four studies [ 40 , 41 , 42 , 43 ]. Meanwhile, CTX alone was evaluated in one study [ 45 ] ( Table 3 ).

Bone turnover markers were evaluated in five of the articles. Variable results were obtained for Serum Procollagen type I N-Terminal propeptide (P1NP) and for Serum collagen type I crosslinked C-telopeptide (CTX). P1NP increased in transwomen and transmen. CTX showed similar values before and after treatment.

PINP in M to F: Bone formation marker PINP increased from 32–49 ng/mL [ 40 ], and from 102–125 ng/mL [ 43 ]. PINP in F to M: Bone formation marker PINP increased from 40 ± 12–50 ± 24 ng/mL [ 42 ]. CTX in M to F: Bone resorption marker, decreased in one study from 0.36 ± 0.16–0.24 ± 0.14 ng/mL [ 40 ], and increased in another study from <0.58 ng/dL to 0.62–1.24 ng/dL [ 43 ]. CTX in F to M: Bone resorption marker CTX increased from 0.20 ± 0.10–0.36 ± 0.15 ng/mL [ 42 ], and was maintained within the normal range [ 41 , 43 ], and decreased from 400 ± 124–302 ± 190 ng/mL [ 45 ].

3.5. Bone Mineral Density (BMD), Method of Evaluation and Anatomical Areas Evaluated

The BMD was evaluated at different anatomical locations: lumbar spine (100%), femoral neck (60%), and less frequently at the total hip, distal forearm, or the whole body [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ].

The method for the evaluation of the BMD was dual-energy X-ray absorptiometry (DXA) (90%). In addition, peripheral quantitative computed tomography (pQCT) was used for the evaluation of the bone architecture (10%) [ 40 , 41 ] ( Table 1 ).

When evaluating the BMD variations related to the time of pharmacotherapy in transwomen (M to F), the range was about 0.4 gr/cm 2 over a 14 year period. Meanwhile, the BMD variation in transmen (F to M) was in the range of 0.6 gr/cm 2 over a nine year period ( Figure 2 ).

Evolution of the mean global bone mineral density (BMD) in transwomen (M to F) over a period of 17 years. Evolution of the mean global bone mineral density (BMD) in transmen (F to M) over a period of 18 years. It can be appreciated the trend toward lower BMD in transwomen compared to transmen.

The BMD value for the longest evaluation period for transwomen (17 year follow-up) was 1.08 gr/cm 2 and for transmen was 1.19 gr/cm 2 (18 years follow-up).

3.6. Risk of Bias Assessment

None of the nine studies were randomized (high risk of bias), there were no deviations from the intended interventions (low risk of bias), there were eight studies missing at least one of the outcomes’ data (high risk of bias), when measured, the outcomes were properly assessed (low risk of bias), and there were no problems with the selection of the reported result (low risk of bias). Overall, there were some concerns related to missing information on outcomes and the lack of randomization ( Figure 3 ).

Risk of bias assessment. From the nine included studies, eight had some concerns and only one study showed an overall high risk of bias. S (study identification), Weight (sample size/number of patients per study).

4. Discussion

The purpose of this systematic review was to evaluate the bone markers and BMD of transwomen (M to F) and transmen (F to M) patients after long-term pharmacotherapy treatment for feminization or virilization with or without sex reassignment surgery.

The obtained information might provide the clinicians with a reference for the bone characteristics of transgender patients receiving long-term hormone therapy and a baseline for studying the future implant site and the peri-implant bone characteristics in this patient population.

There were very few long-term studies (greater than 3 years) [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ], with substantial group variability in age, drug and dosage, time under treatment, and biochemical markers for bone metabolism that precluded the statistical comparisons. Hence, the data was represented as percentages, mean, and standard deviations when feasible.

4.1. Transgender Demographics and Time under Treatment

These data were gathered to understand the trends of the transgender population under pharmacotherapy supplementation. The results showed that the demographics of adult transgender M to F and F to M populations were comparable and the long-term follow-up studies were 100% based on European populations. The longest reported follow-up period extended up to 18 years [ 45 ].

4.2. Type of Pharmacotherapy Received and Dosage

Transgender women (M to F) before and after gonadectomy received different forms of estrogens and testosterone suppressors (cyproterone acetate and spironolactone); meanwhile, transgender men (F to M) received mainly testosterone therapy before and after surgery [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ].

Different dosages and various methods of administration (intraoral, sublingual, intramuscular, patches, implants, and subcutaneous injection) were observed. The differences in pharmacologic treatment were the result of patient-centered approaches more than those that were guided by the specific pharmacological protocol from the treatment center [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ].

4.3. Bone Metabolism Markers and Their Potential Effect on Implant Therapy

Calcium and phosphates are responsible for calcium homeostasis and participate in the acid–base balance and also facilitate the release of growth factors embedded in bone [ 38 ]. The action of the osteoclasts on the calcified bone matrix facilitates its dissolution and releases calcium ions into the blood to form blood calcium [ 46 ]. In a parallel action, the calcium contained in the blood flow can be deposited onto the bone to form bone calcium, mediated by the osteoblasts. These phenomena are regulated by enzymes and hormones (vitamin D, calcitonin, parathyroid hormone, and other metabolites) [ 47 ].

In the presence of metabolic imbalances produced by the cross-sex pharmacologic therapies, the blood calcium balance system can be altered, thereby playing an important role as an ethiological factor for pharmacologically induced osteoporosis [ 48 ].

These pharmacologic therapies can also alter the phosphorus/calcium ratio. The reduction of phosphorus can alter the calcium absorption, while increased phosphorus concentrations can increase the oxidative stress as well as the hormonal balance between phosphates, calcium, and vitamin D. This might be conducive to adverse effects on mineral metabolism and increased bone loss [ 49 , 50 ].

Alkaline phosphatase and osteocalcin are both bone formation markers [ 50 , 51 ]. Bone alkaline phosphatase (ALP) regulates bone mineralization [ 51 ]. There are also liver ALP isoforms that differ only by posttranslational modifications. However, the immunoassays with monoclonal antibodies better recognize bone isoforms [ 52 ]. Meanwhile, osteocalcin is a major non-collagenous protein synthesized by osteoblasts and odontoblasts, and its circulating levels are highly specific for bone formation. It is degraded and excreted by the kidneys [ 53 ].

Calcium and phosphate are an essential part of bone metabolism, and their depletion can result in reduced bone mineral density, changes in the bone structure (increased trabecular spacing and reduction of cortical bone thickness), osteoporosis, and delayed osseointegration [ 54 ]. Not all osteoporotic signs are the result of calcium, phosphate, or vitamin D deficiency, but these are important factors associated with optimal bone health [ 55 , 56 ]. Their depletion can also result from low intake, vitamin D deficiency, and changes in the metabolism induced by disease or medications [ 57 , 58 ].

The results of the present review showed that calcium and phosphate levels, as well as alkaline phosphatase and osteocalcin, remained within similar values after the long-term pharmacotherapy for transgender M to F and F to M patients, thereby demonstrating that the administered therapies had minimal effects on calcium/phosphate balance and alkaline phosphatase and osteocalcin levels [ 37 , 45 ].

4.4. Two Main Bone Turnover Markers

Following the recommendations by the International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry (IFCC) for the quantification of the bone turnover (bone resorption and bone formation processes), the N-terminal pro-peptide of type I procollagen (PINP) and C-telopeptide of type I collagen (CTX-I) were recorded [ 59 ]. Respectively, PINP measures bone formation and CTX-I measures bone resorption [ 59 ].

This review showed that hormone therapy induced an increase in the PINP values in M to F patients (17 ng/mL to 23 ng/mL) and an increase of PINP in F to M patients (>10 ng/mL) [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. Meanwhile, the CTX values in M to F and F to M were inconsistent [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ].

During transgender hormone therapy, the goal is similar to the goal of the antiresorptive treatment—to lower the PINP by at least 10 ng/mL and <35 ng/mL during bone resorption. Meanwhile, during bone formation, the goal is to raise the PINP by at least 10 ng/mL to achieve a level of >69 ng/mL [ 60 ].

Therefore, it seems that the long-term administered pharmacotherapy for M to F and F to M transgender patients can produce a slight increase in the bone formation rates evaluated with the PINP [ 40 , 41 , 42 , 43 ]. It should also be considered that these PINP values can change over time, induced by factors such as age, metabolism changes, and non-compliant treatment interruption [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ].

4.5. Bone Mineral Density (BMD)

The BMD condition of M to F and F to M transgender patients receiving long-term cross-sex pharmacotherapy is contradictory. For Sosa et al. (2003) [ 38 ], Ruetsche et al. (2005) [ 39 ], Van Caenegem et al. 2012 [ 42 ], and Wiepjes et al. 2018 [ 44 ], both M to F and F to M patients will possess a stable or increased BMD compared to matched male or female controls.

The authors explain their findings based on the protective effects of estrogens in M to F patients against bone resorption, mediated by increased serum levels of estradiol [ 38 ], mediated by IGF1 (insulin-like growth factor) [ 39 ]. Meanwhile, in F to M patients, the preservation or increase of the BMD could be produced by the long-term effects of testosterone, reduced estrogen levels, and a muscle mass increase, which, all together, might result in reduced resorption rates [ 38 , 39 , 42 , 44 ].

On the other hand, according to Schlatterer et al. (1998) [ 37 ], Lapauw et al. (2007) [ 40 ], T’Sjoen et al. (2009) [ 41 ], and Wierckx et al. (2012) [ 43 ], the BMD of M to F patients was reduced, and signs of osteoporosis of the lumbar spine and distal arm were observed, but F to M patients did not show reduced BMD. Apparently, the effects of muscle mass reduction, non-compliance to the treatment (which can result in androgen deficiency), inadequate estrogen dosage, and sedentary lifestyles produced the bone resorption experienced by the M to F transgender patients [ 37 , 39 , 40 , 41 , 43 ] ( Table 1 ).

4.5.1. BMD Changes and their Potential Relationship to Dental Implants

The local properties of the future implant bed (bone mineral density and bone structure), as well as the primary implant fixation (primary stability), are essential factors that can reduce micromotion and will allow immediate loading protocols [ 61 , 62 ]. Moreover, bone quality, quantity, implant geometry, and surgical technique have been considered factors that can influence the presence of micromotion or the presence of implant stability [ 63 ]. When the bone mineral density is low, the primary implant stability cannot be achieved unless certain modifications are completed during the implant bed preparation, for example—the use of specific implant designs (tapered, self-tapping) [ 64 ], under-drilling, bone condensation, or osseo-densification techniques [ 65 ].

There is also a link between low bone density, osteoporosis, and implant failure [ 66 ] and low bone density and lower osseointegration [ 67 ]. However, recent systematic reviews showed that the implant survival rates and marginal bone loss of unloaded implants were similar in implants inserted in low-density bone compared to implants inserted in normal-density bone [ 68 , 69 ]. Furthermore, it was reported that low bone mineral density values found in a group of patients with osteoporosis and osteopenia did not influence the implant osseointegration after 24 months of follow-up [ 70 ]. However, when the implant requires higher primary stability (i.e., immediate loading protocols, single-body implants), the bone mineral density is a factor that should be considered before the load protocols are applied [ 71 ]. Marquezan et al. demonstrated that there is a direct association between BMD and primary implant stability (as the bone density increase, the primary stability increase). [ 71 ].

4.5.2. Hypothesis for the Effects of Hormone Therapy for Transgender Patients on BMD and Its Potential Relation to Dental Implants

It seems that there is some risk of reduced BMD in M to F transgender patients receiving long-term cross-sex pharmacotherapy. Therefore, when performing dental implant procedures in such patients, the precautions followed in osteoporotic patients should be considered [ 66 , 67 , 68 , 69 ]. In addition, based on the bone changes observed in the present study over the long-term follow-up, it seems reasonable to monitor bone parameters before procedures involving dental implants in transgender patients [ 72 ]. Finally, when considering the risk factors for long-term implant survival (diabetes mellitus, age, smoking, and immediate loading), the BMD was the most critical factor determining implant survival (lower BMD values resulted in lower implant survival rates) [ 73 ].

4.6. Strengths and Limitations of the Present Work

The strengths of the present paper are that this is the first systematic review that has compiled the effects of the cross-sex pharmacotherapy on bone metabolism markers, BTMs, and BMD. Additionally, strict inclusion and exclusion criteria and adequate calibration were followed by the investigators involved in the data collection and data analysis. Finally, a hypothesis for the potential effects of long-term hormone therapy on dental implant therapy was provided.

There are limitations to the present work—firstly, the low number of studies included and the preclusion of any statistical comparisons; secondly, the exclusion of the effects of short-term (less than 3 years) cross-sex pharmacotherapy and their effects in younger patients. Moreover, the multiple variables that, at a certain point, can affect the bone metabolism and structural characteristics of this population (sex-reassignment surgery and aging) further limit the comparison of treatments.

4.7. Recommended Future Steps

Given the lack of information regarding the effects of hormone therapy in transgender patients on bone healing, implant osseointegration, peri-implant health, and implant survival, clinical studies compiling such information are recommended.

5. Conclusions

Within the limitations of this systematic review, the following conclusions can be drawn:

• Long-term pharmacotherapy for transgender patients does not alter the calcium, phosphate, alkaline phosphatase, and osteocalcin bone markers.
• Long-term pharmacotherapy for transgender patients will slightly increase the bone formation, expressed with increased PINP turnover markers.
• Long-term cross-sex pharmacotherapy for M to F transgender patients will produce a slight reduction in bone mineral density.

Author Contributions

Conceptualization, R.D.-R., and P.S.; Methodology, R.D.-R., G.R. and P.S.; Software, R.D.-R.; Validation, R.D.-R., G.R. and P.S.; Formal Analysis, R.D.-R., G.R. and P.S.; Investigation, R.D.-R., G.R. and P.S.; Resources, R.D.-R. and G.R.; Data Curation, R.D.-R.,G.R. and P.S.; Writing—Original Draft Preparation, R.D.-R., G.R. and P.S.; Writing—Review & Editing, R.D.-R., G.R. and P.S.; Visualization, R.D.-R., G.R. and P.S.; Supervision, R.D.-R.; Project Administration, R.D.-R., G.R. and P.S.; Funding Acquisition, R.D.-R., G.R.

Conflicts of Interest

The authors declare no conflict of interest.

Federal judge temporarily blocks state law banning gender transition care

A federal judge has temporarily blocked an Indiana law that would have prevented doctors from providing gender transition care to minors. 

The law was set to take effect July 1, but on Friday U.S. District Judge for the Southern District of Indiana James Patrick Hanlon issued a preliminary injunction in a lawsuit brought by four transgender youth, their parents and a medical provider who said it violated the U.S. Constitution.  

More: These new Indiana laws affect transgender and other LGBTQ Hoosiers

“Today’s victory is a testament to the trans youth of Indiana, their families, and their allies, who never gave up the fight to protect access to gender-affirming care and who will continue to defend the right of all trans people to be their authentic selves, free from discrimination,” Ken Falk of the ACLU of Indiana, which represents the plaintiffs, said in a prepared statement.  

A spokesperson from Indiana Attorney General Todd Rokita’s office, which is leading the state's defense, said in a statement the decision was a "disappointment" but "not the end of the story."

Hanlon's decision recognizes the unsettled questions around the safety and efficacy of puberty blockers and hormone therapy, the spokesperson said, and how that gives the state reason to regulate these procedures for minors. "Our office will continue to defend the democratically passed laws of the Indiana General Assembly, and we will continue to fight for the children," the spokesperson continued.

The ban targeted cross-sex hormone therapy, puberty-blocking drugs and gender reassignment surgery, according to Hanlon's order. The judge specified that under the injunction the state can't prohibit “gender transition procedures for minors except gender reassignment surgery and ... speech that would aid or abet gender transition procedures for minors" while the lawsuit continues to move through the court.

More: 'I just feel powerless': Trans teens share their stories as new Indiana laws target them

The minors’ request that a judge freeze the ban on gender reassignment surgeries was denied, however, as Hanlon said they “lack standing to challenge that ban because gender reassignment surgeries are not provided to minors in Indiana.” 

If the law were to take effect, physicians who provide these procedures could face discipline by the state’s medical licensing board. 

In their original complaint, which was filed in early April just hours after the law was signed by Gov. Eric Holcomb, the plaintiffs say the care at the heart of the ban is “evidence-based and medically necessary” as it treats minors suffering from gender dysphoria, a widely-recognized condition that can cause serious mental health challenges.

More: Federal judge considers block on Indiana law banning transgender health care for minors

“By denying this medically necessary treatment to minors, the State of Indiana has displaced the judgment of parents, doctors, and adolescents with that of the government,” the lawsuit states. “In so doing, the state has intruded on the fundamental rights of parents to care for their minor children by consenting to their receipt of doctor-recommended and necessary care and treatment.” 

The state argued in its response to the preliminary injunction request that these procedures pose a risk of leaving youth with “irreversible negative medical consequences.” 

More: New Indiana law against sex education in lower grades is too vague, ACLU lawsuit alleges

“The question here is not whether parents have a right to choose among otherwise lawful treatment options but whether they have a right to override legislative judgments that the specific gender transition procedures sought are too risky, unproven, and invasive to be offered to any minor,” the response reads.  

In his decision Hanlon noted that the state has a strong interest in enforcing the laws enacted by democratically-elected officials, but plaintiffs have shown “some likelihood of success” on the claim that their rights – specifically, equal protection rights under the 14th Amendment and freedom of speech rights under the First Amendment - would be infringed upon by the law. 

Contact the reporter at 317-273-3188.

Federal judge temporarily blocks Indiana law banning gender-transition care

A federal judge has temporarily blocked an Indiana law that would have prevented doctors from providing gender transition care to minors. 

The law was set to take effect July 1 but on Friday, U.S. District Judge for the Southern District of Indiana James Patrick Hanlon issued a preliminary injunction in a lawsuit brought by four transgender youth, their parents, and a medical provider who said it violated the U.S. Constitution.  

“Today’s victory is a testament to the trans youth of Indiana, their families, and their allies, who never gave up the fight to protect access to gender-affirming care and who will continue to defend the right of all trans people to be their authentic selves, free from discrimination,” Ken Falk of the ACLU of Indiana, which represented the plaintiffs, said in a prepared statement.  

The Indianapolis Star, a member of the USA TODAY Network, has requested comment from Indiana Attorney General Todd Rokita’s office, which represents the state in court and is one of the defendants.

The ban targeted cross-sex hormone therapy, puberty-blocking drugs and gender reassignment surgery, according to Hanlon's order. The judge specified that under the injunction the state can't prohibit “gender transition procedures for minors except gender reassignment surgery and ... speech that would aid or abet gender transition procedures for minors" while the lawsuit continues to move through the court.

The minors’ request that a judge freeze the ban on gender reassignment surgeries was denied, however, as Hanlon said they “lack standing to challenge that ban because gender reassignment surgeries are not provided to minors in Indiana.” 

Those who back the law say it would protect kids from making life-changing decisions at an age where they’re too young to understand the consequences. Opponents say the care targeted by the law is life-saving, and that the ban would end parents’ rights to make medical decisions on behalf of their children.  

If the law were to take effect, physicians who provide these procedures could face discipline by the state’s medical licensing board. 

Sex, Gender, and Drug Use

• Sex and gender differences may affect a person’s drug use and the development and treatment of substance use disorders. Biological sex factors such as brain and endocrine system functions influence how the body responds to drugs. For example, while men are more likely than women to use illicit drugs, women who use drugs may progress more quickly from drug use to addiction.
• Factors related to gender identity and gender roles, including stigma and discrimination , family and community life, mental health, and financial stability, can also affect a person’s substance use and likelihood of developing a substance use disorder. Sex, gender, and gender identity also affect treatment for substance use disorders, influencing rates of care seeking, access and barriers to care, and responses to some medications.
• NIDA supports research to understand sex and gender differences in how substances affect people, including during pregnancy and early childhood . NIDA also funds research into the specific substance use disorder risk factors, treatment, and harm reduction needs of women and gender minorities.  

Substance Use in Women Research Report

Examines women and substance use and sex and gender differences in drug addiction treatment.

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Find more information about sex, gender, and substance use.

• See research updates  from the National Institute of Health’s Office of Research on Women’s Health.
• Find general information on women’s health issues from the U.S. Department of Health and Human Services Office on Women’s Health.
• Read about women and mental health on the National Institute of Mental Health website.
• See information for women about quitting smoking from the National Cancer Institute.
• Find more women’s health resources from the U.S. Food & Drug Administration.