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What Is Gender-Affirming Hormone Therapy?

  • How to Get Started
  • Masculinizing Therapy
  • Feminizing Therapy
  • What to Expect
  • Access to Treatment

Gender-affirming hormone therapy helps transgender and other gender-nonconforming people align their bodies with their gender identity . Not all transgender (trans) people are interested in hormone therapy. However, many transgender people, particularly binary transgender people, turn to hormones to affirm their gender.

Gender-affirming hormone therapy is comprised of masculizing hormone therapy used in trans men and feminizing hormone therapy used in trans women.

This article describes the goals of gender-affirming hormone therapy, how the treatment is administered, and the different types of hormones used. It also explains what to expect when undergoing gender-affirming hormone therapy and the possible risks.

Verywell / Brianna Gilmartin

Definitions

The term "gender affirmation" is preferred over "gender confirmation" because a transgender person does not need to confirm their gender to anyone. The word "confirm" suggests proof, while "affirm" means to assert strongly.

Who Is Gender-Affirming Hormone Therapy For?

Gender-affirming hormone therapy is the primary medical treatment sought by transgender people. It allows their secondary sex characteristics to be more aligned with their individual gender identity.

Gender-affirming hormone therapy comes in two types:

  • Masculinizing hormone therapy used to develop typically male sex characteristics
  • Feminizing hormone therapy used to develop typically female sex characteristics

Hormone therapy can be used on its own for people who have no interest in pursuing gender-affirming surgery . It can also be used in advance of surgery (usually for six months to one year) to improve the outcomes of surgery, such as breast augmentation.

According to the National Transgender Discrimination Survey, 95% of transgender people and 49% of non-binary people were interested in hormone therapy.

Hormone Therapy vs. Puberty Blockers

Puberty blockers are used to delay the onset of puberty in young, gender-diverse people prior to the start of hormone therapy. They are considered to be a distinct but complementary component of gender-affirmation therapy.

How to Get Started 

Gender affirmation is a process in which hormones only play a part. It typically starts with social gender affirmation in which you alter your appearance, wardrobe, and manner of grooming while updating your name, pronouns, and legal documentation.

Medical gender affirmation is typically the next step in which you work with a healthcare provider to identify your personal goals and which type of types of treatments are needed to achieve those goals.

Hormone therapy is typically overseen by a specialist in the endocrine (hormonal) system called an endocrinologist . Other healthcare providers trained in gender-affirming medical care may be equally qualified to administer treatment.

Depending on state law and other factors, healthcare providers may be able to dispense treatment on the same day. No letter from a mental health provider may be needed. Call Planned Parenthood or your local LGBTI organization to learn about the laws in your state.

To receive authorization for insurance coverage, many insurers require a diagnosis of gender dysphoria . To do so, a therapist or mental health professional must confirm that there is a mismatch between a person's expressed or experienced gender and the gender they were assigned at birth for a period of at least six months.

How to Choose the Right Provider

Not every endocrinologist is equally well-suited to administer gender-affirming hormone therapy. Those who have undergone a comprehensive, multidisciplinary gender-affirmation training program are generally preferred.

Do not hesitate to ask about a healthcare provider's experience and qualifications in administering gender-affirming care.

Masculinizing Hormone Therapy

Masculinizing hormone therapy uses various types of testosterone to promote masculinizing changes in both binary and non-binary individuals. Testosterone is most often given as an injection, but other formations are available, including pills and creams.

There has been growing interest in the use of subcutaneous pellets for testosterone treatment, as they only need to be inserted two to four times a year. However, they are not always available or covered by insurance.

Form  Drug  Dose in milligrams (mg)
Oral Testosterone undecanoate    160–240 mg per day
Injected Testosterone enanthate or cypionate   50–200 mg per week or 100–200 mg every 2 weeks
Testosterone undecanoate 1,000 mg every 12 weeks
Transdermal Testosterone 1% gel 2.5 to 10 mg per day
Testosterone patch  2.5 to 7.5 mg per day

Changes that can be induced by masculinizing hormone therapy include:

  • Facial and body hair growth
  • Increased muscle mass
  • Lowering of the pitch of the voice
  • Increased sex drive
  • Growth of the glans clitoris
  • Interruption of menstruation
  • Vaginal dryness
  • Facial and body fat redistribution
  • Sweat- and odor-pattern changes
  • Hairline recession; possibly male pattern baldness
  • Possible changes in emotions or interests

Masculinizing hormone therapy cannot reverse all of the changes associated with female puberty. If transmasculine individuals have experienced breast growth that makes them uncomfortable, they may need to address that with binding or top surgery .

Testosterone will also not significantly increase height unless it is started reasonably early. Finally, testosterone should not be considered an effective form of contraception, even if menses have stopped.

Feminizing Hormone Therapy

Feminizing hormone therapy uses a combination of estrogen and a testosterone blocker. The testosterone blocker is needed because testosterone has stronger effects on the body than estrogen.

The blocker most commonly used in the United States is spironolactone , a medication also used for heart disease. The medication used as a puberty blocker, called Supprelin LA (histerline), can also be used to block testosterone.

Various forms of estrogen can be used for feminizing hormone therapy. In general, injectable or topical forms are preferred as they tend to have fewer side effects than oral estrogens. However, some trans women prefer oral estrogens.

 Form  Drug  Dose in milligrams (mg)
Oral Conjugated estrogens 2.5 to 7.5 mg per day
  17-beta estradiol 2.0 to 6.0 mg per day
Injected Estradiol valerate  5.0 to 20 mg every 2 weeks
  Estradiol cypionate 2.0 to 10 mg every week
Transdermal Estradiol patch 0.1 to 0.4 mg twice weekly

Changes that can be induced by feminizing hormone therapy include:

  • Breast growth
  • Softening of the skin
  • Fat redistribution
  • Reduction in face and body hair (but not elimination)
  • Reduced hair loss/balding
  • Muscle-mass reduction
  • Decrease in erectile function
  • Testicular size reduction

Estrogen cannot reverse all changes associated with having undergone testosterone-driven puberty. It cannot eliminate facial or body hair or reverse shoulder width, jaw size, vocal pitch, or facial structure. Many of these can be addressed with aesthetic or surgical treatments.

What to Expect During Treatment

Some hormones used for gender-affirming hormone therapy are self-administered or given by someone you know. Others need to be administered by a healthcare provider.

Thereafter, regular follow-ups are needed to evaluate the effects of treatment and possible side effects. Most healthcare providers recommend visiting every 3 months for the first year and every 6 to 12 months thereafter.

Effects of Therapy

It can take three to five years for your body to show the full effects of gender-affirming hormone therapy. Some changes can occur within the first six months, such as the development of larger breasts. Others, like changes in facial structure, can take years.

In addition to physical changes, hormone therapy can cause emotional changes. If you are sexually active, it may improve sexual satisfaction as well as your overall sense of well-being. Hormone therapy can also help to ease the stress associated with gender dysphoria.

If you discontinue therapy, some changes may be reversible. Others like changes in bone structure may be permanent.

Possible Risks

As beneficial as gender-affirming hormone therapy can be, it also carries certain risks depending on which hormone you are taking.

Possible risks of feminizing hormone therapy include:

  • High blood pressure
  • Blood clots
  • Heart disease
  • Type 2 diabetes
  • Weight gain
  • Infertility
  • Breast and prostate cancer

Risks of masculinizing hormone therapy:

  • Male pattern baldness
  • High cholesterol
  • Pelvic pain
  • Sleep apnea
  • Interfertility

Access to Gender-Affirming Hormone Therapy

Until relatively recently, access to gender-affirming hormone therapy was largely managed through gatekeeping models that required gender-diverse people to undergo a psychological assessment before they could access hormone treatment.

However, there has been a growing movement toward the use of an informed consent model to better reflect access to other types of medical care. This change has been reflected in the standards of care for transgender health produced by the World Professional Association of Transgender Health (WPATH).

Gender-affirming hormone therapy is considered to be a medically necessary treatment for gender dysphoria. It should be covered by most insurers in the United States after legal changes that occurred as part of the passage of the Affordable Care Act.

However, state laws vary substantially in terms of transgender protections, and some states do allow policies to exclude various aspects of transgender health care, including gender-affirming hormone therapy.

Access to hormone therapy can be prohibitively expensive for many people if they need to pay out of pocket, which may lead some people to try to get these medications from friends or other unlicensed sources.

In addition, individuals who are involved with carceral systems such as immigrant detention may be denied access to hormones. This can have significant negative physical and psychological effects.

Gender-affirming hormone therapy is the primary form of treatment for transgender people. Masculizing hormone therapy involving testosterone is used to develop secondary male sex characteristics like larger muscles. Feminizing hormone therapy involving estrogen and a testosterone blocker is used to develop secondary female sex characteristics like breasts.

Some masculinizing and feminizing effects can occur within months, while others may take years. If you stop treatment, many of the effects will reverse while some will be permanent. Regular follow-up care is needed to avoid potential side effects and long-term complications.

Gardner I, Safer JD. Progress on the road to better medical care for transgender patients . Curr Opin Endocrinol Diabetes Obesity . 2013 20(6):553-8. doi:10.1097/01.med.0000436188.95351.4d

James SE, Herman JL, Rankin S, Keisling M, Mottet M, Anafi M. The Report of the 2015 U.S. Transgender Survey . Washington, DC: National Center for Transgender Equality. 2016.

Planned Parenthood. Gender-affirming hormone therapy: what to expect on your first visit and beyond .

Boskey ER, Taghinia AH, Ganor O. Association of surgical risk with exogenous hormone use in transgender patients: A systematic review . JAMA Surg . 2019;154(2):159-169. doi:10.1001/jamasurg.2018.4598

Almazan AN, Benson TA, Boskey ER, Ganor O. Associations between transgender exclusion prohibitions and insurance coverage of gender-affirming surgery. LGBT Health . 2020;7(5). doi:10.1089/lgbt.2019.0212

White Hughto JM, Reisner SL. A systematic review of the effects of hormone therapy on psychological functioning and quality of life in transgender individuals . Transgender Health . 2016;1(1),21–31. doi:10.1089/trgh.2015.0008

Cavanaugh T, Hopwood R, Lambert C. Informed consent in the medical care of transgender and gender-nonconforming patients . AMA Journal of Ethics . 2016;18(11),1147–1155. doi:10.1001/journalofethics.2016.18.11.sect1-161

World Professional Association for Transgender Health. Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People (7th Version) . WPATH. 2011.

By Elizabeth Boskey, PhD Boskey has a doctorate in biophysics and master's degrees in public health and social work, with expertise in transgender and sexual health.

Transgender Hormone Therapy

Transgender men and women desire a permanent identity as a member of the gender with which they identify. This transition usually involves hormonal therapy and may also involve surgery.

We offer hormonal therapy for transgender individuals. People seeking transgender surgery are referred to well-established health care facilities that specialize in this procedure.

Hormonal Therapy

Transgender hormonal therapy (also called hormonal reassignment) allows development of secondary sexual characteristics that reflect the person's preferred gender identity.

Hormonal therapy for transgender people replaces the hormones naturally occurring in their bodies with those of the other sex.

  • Woman-to-man hormonal treatment (testosterone treatment) is provided to promote male characteristics, such as a male pattern of body hair, a male voice and a male physical shape. The treatment also results in stopping monthly menstruation.
  • Man-to-woman hormonal treatment is provided to inhibit male characteristics and promote feminine characteristics, such as breast formation and elimination of body hair growth.

Both male hormones (androgens) and female hormones (estrogens) are present in men and women alike, but in vastly different amounts. Giving the right amount of the right hormone is important in the life-long management of transgender hormonal therapy.

Psychological Evaluation

To obtain sex reassignment therapy, a full psychological or psychiatric evaluation by a certified professional will be performed prior to the start of hormonal therapy. This is important to ensure that the diagnosis of transgender re-assignment is not clouded by an underlying psychiatric disorder. 

A local transgender program called Pathways  offers professional and supportive programs dealing with issues of gender identity. Pathways also offers psychiatric evaluations to program participants, as well as information, guidance about resources and peer group support.

Therapy Based on Guidelines

Initial care includes a physical exam and blood test to check the individual’s overall health. Hormonal therapy is geared to an individual’s goals and therapy is monitored by clinical response and blood tests. Therapies are adjusted as needed based on response. Hormones are given as oral or injected medications.

Therapy is based on care standard guidelines established by The Endocrine Society called Endocrine Treatment of Transgender Persons. The guidelines were developed by a task force of content experts and co-sponsored by the European Society of Endocrinology, European Society of Pediatric Endocrinology, Lawson Wilkins Pediatric Endocrine Society, and the World Professional Association for Transgender Health. The guidelines address treatment of adolescents, hormonal therapy for transgender adults, long-term care and sex re-assignment surgery.

People who desire transgender hormonal therapy are encouraged to see a trained medical professional, who will prescribe the right medications and monitor your care over time. The physician carefully watches for complications as you slowly begin taking an increased level of hormones.

Physicians throughout Wisconsin refer their patients to us for transgender hormonal therapy. We share our expertise with these community physicians so they can continue local care for their patients.

More to Explore

Viry Gomez and family

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.

28. Safer JD, Pearce EN. A simple curriculum content change increased medical & student comfort with transgender medicine. Endocrine Pract 2013; 33:39–44.

  • Patient Care & Health Information
  • Tests & Procedures
  • Masculinizing hormone therapy

Masculinizing hormone therapy typically is used by transgender men and nonbinary people to produce physical changes in the body that are caused by male hormones during puberty. Those changes are called secondary sex characteristics. This hormone therapy helps better align the body with a person's gender identity. Masculinizing hormone therapy also is called gender-affirming hormone therapy.

Masculinizing hormone therapy involves taking the male hormone testosterone. It stops menstrual cycles and decreases the ovaries' ability to make estrogen. Masculinizing hormone therapy can be done alone or along with masculinizing surgery.

Not everybody chooses to have masculinizing hormone therapy. It can affect fertility and sexual function, and it might lead to health problems. Talk with your health care provider about the risks and benefits for you.

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Why it's done

Masculinizing hormone therapy is used to change the body's hormone levels. Those hormone changes trigger physical changes that help better align the body with a person's gender identity.

In some cases, people seeking masculinizing hormone therapy experience discomfort or distress because their gender identity differs from their sex assigned at birth or from their sex-related physical characteristics. This condition is called gender dysphoria.

Masculinizing hormone therapy can:

  • Improve psychological and social well-being
  • Ease psychological and emotional distress related to gender
  • Improve satisfaction with sex
  • Improve quality of life

Your health care provider might advise against masculinizing hormone therapy if you:

  • Are pregnant
  • Have a hormone-sensitive cancer, such as breast cancer
  • Have problems with blood clots, such as when a blood clot forms in a deep vein, a condition called deep vein thrombosis, or a there's a blockage in one of the pulmonary arteries of the lungs, called a pulmonary embolism
  • Have significant medical conditions that haven't been addressed
  • Have behavioral health conditions that haven't been addressed
  • Have a condition that limits your ability to give your informed consent

There is a problem with information submitted for this request. Review/update the information highlighted below and resubmit the form.

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Research has found that masculinizing hormone therapy can be safe and effective when delivered by a health care provider with expertise in transgender care. Talk to your health care provider about questions or concerns you have regarding the changes that will happen in your body as a result of masculinizing hormone therapy.

Complications can include:

  • Weight gain
  • Developing male-pattern baldness
  • Sleep apnea
  • A rise in cholesterol, which may increase the risk of heart problems
  • High blood pressure
  • Making too many red blood cells — a condition called polycythemia
  • Type 2 diabetes
  • Blood clots in a deep vein or in the lungs
  • Infertility
  • Drying and thinning of the lining of the vagina
  • Pelvic pain
  • Discomfort in the clitoris

Evidence suggests that people who have masculinizing hormone therapy don't have an increased risk of breast cancer, endometrial cancer or heart disease when compared to cisgender women — women whose gender identity aligns with societal norms related to their sex assigned at birth.

It's unclear whether masculinizing hormone therapy raises the risk of ovarian and uterine cancer. Further research is needed.

To minimize risk, the goal for people taking masculinizing hormone therapy is to keep hormone levels in the range that's typical for cisgender men.

Masculinizing hormone therapy might limit your fertility. If possible, it's best to make decisions about fertility before starting treatment. The risk of permanent infertility increases with long-term use of hormones. That is particularly true for those who start hormone therapy before puberty begins. Even after stopping hormone therapy, your ovaries and uterus might not recover enough for you to become pregnant without infertility treatment.

If you want to have biological children, talk to your health care provider about your choices. They may include:

  • Egg freezing. This procedure also is called mature oocyte cryopreservation. Egg freezing has multiple steps that involve triggering ovulation, retrieving the eggs and then freezing them.
  • Embryo freezing. This process also is known as embryo cryopreservation. If you want to freeze embryos, you'll need to have the eggs fertilized before they are frozen.
  • Ovarian tissue cryopreservation. With this procedure, ovarian tissue is removed, frozen, and later thawed and reimplanted.

Although testosterone might limit your fertility, you still can become pregnant if you have your uterus and ovaries and you have sex with a person who produces sperm. If you want to avoid pregnancy, use birth control consistently. Talk with your health care provider about the form of birth control that's best for your situation.

How you prepare

Before you start masculinizing hormone therapy, your health care provider assesses your health. This helps address any medical conditions that might affect your treatment. The evaluation may include:

  • A review of your personal and family medical history
  • A physical exam
  • A review of your vaccinations
  • Screening tests for some conditions and diseases
  • Identification and management, if needed, of tobacco use, drug use, alcohol use disorder, HIV or other sexually transmitted infections
  • Discussion about birth control, fertility and sexual function

You also might have a behavioral health evaluation by a provider with expertise in transgender health. The evaluation may assess:

  • Gender identity
  • Gender dysphoria
  • Mental health concerns
  • Sexual health concerns
  • The impact of gender identity at work, at school, at home and in social settings
  • Risky behaviors, such as substance use or use of unapproved hormone therapy or supplements
  • Support from family, friends and caregivers
  • Your goals and expectations of treatment
  • Care planning and follow-up care

People younger than age 18, along with a parent or guardian, should see a medical care provider and a behavioral health provider with expertise in pediatric transgender health to discuss the risks and benefits of hormone therapy and gender transitioning in that age group.

What you can expect

You should start masculinizing hormone therapy only after you've had a discussion of the risks and benefits as well as treatment alternatives with a health care provider who has expertise in transgender care. Make sure you understand what will happen and get answers to any questions you may have before you begin hormone therapy.

Masculinizing hormone therapy typically begins by taking testosterone. A low dose of testosterone is prescribed, and then the dose is slowly increased over time. Testosterone usually is given through a shot, also called an injection, or through a gel or patch applied to the skin. Other forms of testosterone that may be appropriate for some people include testosterone pellets placed under the skin, a prolonged action injection and an oral capsule taken twice a day.

The testosterone that's used for masculinizing hormone therapy is identical to the hormone that the testicles and ovaries make naturally. Don't use synthetic androgens, such as oral methyl testosterone or anabolic steroids. They can harm your liver and cannot be accurately monitored.

After you begin masculinizing hormone therapy, you'll notice the following changes in your body over time:

  • Menstruation stops. This will occur within 2 to 6 months of starting treatment.
  • Voice deepens. This will begin 3 to 12 months after you start treatment. You'll see the full effect within 1 to 2 years.
  • Facial and body hair grows. This will begin 3 to 6 months after treatment starts. The full effect will happen within 3 to 5 years.
  • Body fat is redistributed. This will begin within 3 to 6 months. You'll see the full effect within 2 to 5 years.
  • Clitoris become larger, and the vaginal lining thins and become drier. This will begin 3 to 12 months after treatment starts. The full effect will happen in about 1 to 2 years.
  • Muscle mass and strength increases. This will begin within 6 to 12 months. You'll see the full effect within 2 to 5 years.

If menstrual bleeding doesn't stop after you've taken testosterone for several months, your health care provider might recommend that you take medicine to stop it.

Some of the physical changes caused by masculinizing hormone therapy can be reversed if you stop taking testosterone. Others, such as a deeper voice, a larger clitoris, scalp hair loss, and increased body and facial hair, cannot be reversed.

While on masculinizing hormone therapy, you meet regularly with your health care provider to:

  • Keep track of your physical changes.
  • Monitor your hormone levels. Over time, your dose of testosterone may need to change to ensure you are taking the lowest dose necessary to get the physical effects that you want.
  • Have lab tests to check for changes in your cholesterol, blood sugar, blood count, liver enzymes and electrolytes that could be caused by hormone therapy.
  • Monitor your behavioral health.

You also need routine preventive care. Depending on your situation, this may include:

  • Breast cancer screening. This should be done according to breast cancer screening recommendations for cisgender women your age.
  • Cervical cancer screening. This should be done according to cervical cancer screening recommendations for cisgender women your age. Be aware that masculinizing hormone therapy can cause your cervical tissues to thin. That can look like a condition called cervical dysplasia in which unusual cells are found on the surface of the cervix. If you have questions or concerns about this, talk to your health care provider.
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  • Tangpricha V, et al. Transgender men: Evaluation and management. https://www.uptodate.com/contents/search. Accessed Sept. 26, 2022.
  • Erickson-Schroth L, ed. Medical transition. In: Trans Bodies, Trans Selves: A Resource by and for Transgender Communities. 2nd ed. Kindle edition. Oxford University Press; 2022. Accessed Sept. 26, 2022.
  • Coleman E, et al. Standards of care for the health of transgender and gender diverse people, version 8. International Journal of Transgender Health. 2022; doi:10.1080/26895269.2022.2100644.
  • AskMayoExpert. Feminizing or masculinizing hormone therapy. Mayo Clinic; 2022.
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Hormone therapy in female-to-male transgender patients: searching for a lifelong balance

  • Original Article
  • Published: 07 October 2020
  • Volume 20 , pages 151–159, ( 2021 )

Cite this article

gender reassignment hormone therapy female to male

  • Luca Maria Schönauer 1 ,
  • Miriam Dellino   ORCID: orcid.org/0000-0003-3522-4648 2 ,
  • Matteo Loverro 3 ,
  • Carmine Carriero 1 ,
  • Teresa Capursi 1 ,
  • Claudia Leoni 4 ,
  • Giuseppe Loverro 1 &
  • Edoardo Di Naro 1  

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Reassignment of a female-to-male (FtM) person requires gender-affirming, androgenic hormonal treatment that is planned to induce appropriate structural changes. This therapy must be prolonged long term, even after the sex reassignment surgery (SRS). The purpose of this study is to evaluate the effects of hormone therapy with testosterone in FtM subjects during a 24-month follow-up in order to highlight the occasional need for early decompensation and to make adequate hormone therapy modulations.

Fifteen out of 23 FtM persons had been previously treated with SRS, while eight were still awaiting surgery. During hormone therapy, both groups were followed for 24 months, with evaluation of desired changes, adverse effects, and functional or metabolic indicators.

In the group of operated FtM subjects (15/23), a significant increase of total testosterone (total T) and free testosterone (free T) was found after 24 months. Luteinizing hormone (LH) maintained a low level, decreasing after ovariectomy, while FSH increased. Voice deepening, facial and body hair variation, male-pattern balding, and body mass index (BMI) increase are all physical changes due to androgenization. In both groups of patients who have been closely monitored, the side effects and thromboembolic, metabolic, and cardiovascular risks of androgen therapy, even in the long term, appear to be irrelevant.

Total T, free T, and LH dosages are shown to be reliable markers of correct androgenization. Strict monitoring of lipid profile, evaluation of BMI and hematocrit, avoidance of self-initiated therapeutic modifications, adherence to a healthy lifestyle, and avoidance of excessive daily calorie intake can limit risks linked to long-term testosterone administration.

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Availability of data and materials

The datasets used during the current study are available from the corresponding author on reasonable request.

This research project was supported in part by the Unit of Obstetrics and Gynecology—University of Bari Aldo Moro, Bari, Italy.

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Department Interdisciplinary Medicine, Unit of Obstetrics and Gynecology, University of Bari “Aldo Moro”, Bari, Italy

Luca Maria Schönauer, Carmine Carriero, Teresa Capursi, Giuseppe Loverro & Edoardo Di Naro

Interdisciplinary Department of Medicine, Gynecology and Ostetrics Clinic, University of Bary, Bari, Italy

Miriam Dellino

Department of Obstetrics and Gynaecology, ASTT Lecco, Ospedale Leopoldo Mandic, Merate, Italy

Matteo Loverro

Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, CNR, Bari, Italy

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Schönauer, L.M., Dellino, M., Loverro, M. et al. Hormone therapy in female-to-male transgender patients: searching for a lifelong balance. Hormones 20 , 151–159 (2021). https://doi.org/10.1007/s42000-020-00238-2

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DOI : https://doi.org/10.1007/s42000-020-00238-2

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Transgender Counseling and Letter Recommending Hormone Replacement Therapy

How a counselor, therapist, diagnostician or psychologist provides professional care to transgender individuals who seek assistance in gender reassignment..

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Counselors may utilize the  Standards of Care (SOC) . The Standards of Care provide clinical guidance to healthcare professionals. These guidelines are flexible and be tailored uniquely to each client. Once a counselor has found that you are mentally prepared to begin HRT (Hormone Replacement Therapy), you will receive two letters. One letter will be a recommendation for hormones. The other letter will be for surgery. Sometimes therapists combine the letters into one. The Standards of Care are helpful to look over because they are the standard guidelines professionals follow for sexual transition: The minimum amount of therapy required by these standards is 3 months. Keep in mind that they are merely guidelines, but they do seem to be adhered to fairly strictly. The therapists judgments stem from your mental readiness to start transitioning. It is the therapists responsibility to make sure that you are emotionally ready to take on such a huge endeavor. She/He needs, among other things, will make sure that:

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  • Transitioning will help, not hurt you

Learn more about the Standards of Care .

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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 ).

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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.

Author,
Year of Publication, Location
SampleTime Receiving the TreatmentHormone and DosageMethod of Evaluation for the Bone Mineral Density (BMD) and Area of EvaluationBone Mineral Density (Adjusted)Study Conclusions Related to Bone Structure, Bone Metabolism and BMD
M to F TranswomenF to M TransmenM to FF to M Before OR ControlsAfter OR Test
[ ] 101011.5 yearsParenteral high doses of estrogens + Cyproterone Acetate or Estrogens alone (2–8 mg/day)Parenteral testosterone esters (250 mg every 2–4 weeks)Conventional whole-body CT scannerM to F195 ± 20 mgr/ccm174 ± 3 mgr/ccmSlight reduction in the BMD of M to F M to F and F to M transsexuals treated with the proposed cross-gender hormone concept possess low risk of osteoporotic change
F to M174 ± 3 mgr/ccm172 ± 2 mgr/ccm
[ ] 53-201 ± 108 months or (16.75 ± 9) yearsEthinyl oestradiol + ciproterone acetate, -Oral estrogens and oestradiol valerate Specific dosages were not provided-Densitometer BMD of the lumbar spine and femoral neckM to FLumbar Spine 1.002 ± 0.155 (gr/cm )Lumbar Spine 1.091 ± 0.150 (gr/cm )The chronic administration of estrogens in men may produce an increase in serum estradiol, a decrease in free testosterone levels, and an increase in BMD—Both in lumbar spine and in femoral neck. This study suggests that the bone of adult men is sensitive to estrogens.
Femoral Neck 0.808 ± 0.135 (gr/cm )Femoral Neck 0.904 ± 0.135 (gr/cm )
[ ] 241512.5 years M-F 2.1 years before surgery and 9.7 years after surgery F-M 1.3 Years before surgery and 6.1 years after surgeryCyproterone acetate 2 mg/day + Ethinyl
estradiol 35 µg/day or a free combination of Cyproterone acetate 2 mg/day + Ethinyl estradiol 35–100 µg/day After surgery, Estradiol valerate or Micronized 17-beta estradiol 2–4 mg/day.
Parenteral testosterone esters 250 mg/IM every 3 weeks Continued after surgeryDual-energy X-ray absorptiometry (DXA) BMD of the lumbar spine, femoral neck, whole body, distal epiphysis, and other 5 areasM to FLumbar spine 1.078 ± 0.131 (gr/cm )Lumbar spine 1.056 ± 0.137 (gr/cm )Biochemical values of calcium phosphate metabolism parameters were within normal ranges and comparable across groups. In transsexual genetic males and females under long term cross-sex hormone treatment, BMD values are generally preserved or increased. Non-compliance with cross-sex hormone treatment may lead to low BMD, only in genetic males. IGF-1 (Insulin like growth factor) could play a role in the mediation of the effect of androgens on bone in F-M transsexuals.
Femoral neck 0.835 ± 0.100 (gr/cm )Femoral Neck 0.774 ± 0.095 (gr/cm )
-Whole body 1.216 ± 0.098 (gr/cm )
F to MLumbar spine 1.100 ± 0.139 (gr/cm )Lumbar spine 1.075 ± 0.088 (gr/cm )
Femoral neck 0.937 ± 0.121 (gr/cm )Femoral Neck 0.842 ± 0.058 (gr/cm )
-Whole body 1.179 ± 0.035 (gr/cm )
[ ] 23->3 years At least 3 years under hormone treatment. Al the patients had sex reassignment surgeryBefore surgery Cyproterone acetate 50–100 mg/day + ethinyl estradiol 25–50 μg/day After surgery either: -Ethinyl estradiol 25–50 μg/day (8 participants) -Estradiol valerate 2 mg/day (10 participants) -Conjugated equine estrogens1.25 mg/day (2 participants) -Transdermal estradiol gels (3 persons)-Dual-energy X-ray absorptiometry (DXA) BMD at the lumbar spine, distal forearm and Peripheral quantitative computed tomography (pQCT), at the same areas for analysis of the bone architectureM to FLumbar spine 1.05 ± 0.11 (gr/cm )Lumbar spine 0.92 ± 0.14 (gr/cm )M to F transsexual persons presents: Lower muscle mass and strength and higher fat mass Lower trabecular bone density and BMD at various sites and smaller cortical bone size as compared to healthy age- and height-matched controls. The lower level of sports-related physical activity as well as the pharmacological and surgical withdrawal from endogenous T production could contribute to these findings. Male-to-female transsexuals may be at increased risk for developing osteoporosis and related fractures. Bone health should be a parameter of interest in the long-term follow-up care for male-to-female transsexual persons.
Distal forearm 0.49 ± 0.05 (gr/cm )Distal forearm 0.42 ± 0.07 (gr/cm )
[ ] 50->3 years and at least 1 year after sex reassignmentCyproterone acetate 50–100 mg/day (1 year) + exogenous estrogen administration-Dual-energy X-ray absorptiometry (DXA) BMD at the lumbar spine, proximal femur and the distal radius of the nondominant site AND pQCT for the analysis of bone architectureM to F-Lumbar spine 0.959 ± 0.159Low bone mass, smaller bone size, and reduced muscle mass. Are highly prevalent in the described group of M-F transsexual persons Androgen deficiency or an inadequate estrogen dosage could be the cause Hormonal protocols differ between different centers and individual changes in BMD are highly variable
There is a need for longitudinal single- and multi-center data on low bone mass risk in the M/F transsexual group.
Total hip 0.940 ± 0.150
Radius and 0.432 ± 0.077
[ ] -66
50 undergone surgery and received hormone therapy 16 Just hormone therapy
8.7 years after sex reassignment surgery (SRS) with a minimum of 9 months and a maximum of 22 years.-Testosterone decanoate 100 mg, Testosterone isocaproate OR fenylpropionate 60 mg, Testosterone propionate 30 mg/mL; 2–3 weeks (35 patients); Testosterone undecanoate 1000 mg; 12 weeks (7 patients); Transdermal testosterone 50 mg daily (8 patients) Testosterone undecanoate 40 mg/day + testosterone gel 50 mg per 5 g, 50 mg daily (1 Patient)Dual-energy X-ray absorptiometry (DXA); BMD at the lumbar spine, and left proximal femur (total hip and femoral neck region)F to MLumbar spine 1.06 ± 0.11 (gr/cm )Lumbar spine 1.03 ± 0.10 (gr/cm )Transmen (F-M) with hormone treatment and after SRS possess a bone and body composition comparable to men, compared with age-matched female controls. This is less fat mass, more central pattern of adiposity, more muscle mass, strength, and larger cortical bone size. The differences may result from the effects of long-term testosterone administration and of diminished estrogen exposure and/or from indirect effects through muscle mass and strength. Transsexual men (F to M) on long-term hormonal therapy do not have an increased risk of low bone mass but associated cardiovascular risk factors are important to address.
Femoral neck 0.84 ± 0.10 (gr/cm )Femoral neck 0.82 ± 0.11 (gr/cm )
Total hip 0.95 ± 0.10 (gr/cm )Total hip 0.96 ± 0.12 (gr/cm )
[ ] 5050±10 yearsBefore surgery Cyproterone acetate 50–100 mg/day/1 year different +exogenous estrogen After surgery all received estrogens (3 patients did not followed the estrogen protocol)TestosteroneDual-energy X-ray absorptiometry (DXA); BMD at the lumbar spine, at the proximal femur (total hip region), and a both distal forearmsM to FData not shownData not shownAfter an average of 10 years of hormone treatment no important side effects were reported and osteoporosis was not observed in transsexual men (F to M). Transsexual women (M to F) suffered from osteoporosis at the lumbar spine and distal arm. Twelve percent of transsexual women (M to F) experienced thromboembolic and/or other cardiovascular events during hormone treatment, possibly related to older age, estrogen treatment, and lifestyle factors. In order to decrease cardiovascular morbidity, more attention should be paid to decrease cardiovascular risk factors during hormone therapy management.
F to MData not shownData not shown
[ ] 71154310 yearsOral or transdermal estrogens and anti-androgens until gonadectomyOral, transdermal, or intramuscular testosterone.Dual-energy X-ray absorptiometry (DEXA) at 2, 5, and 10 years Absolute BMDM to FMale and Female adult reference population0.956 (+0.006) (gr/cm )This study showed that hormone therapy does not negatively affect the BMD Regularly assessing BMD should be completed just when osteoporotic risk is present (>60 years age) High percentage of low BMD was found prior to hormone therapy in transwomen. Therefore, evaluation of BMD before start of hormone therapy may be considered.
F to MMale and Female adult reference population1.45 (+0.008) (gr/cm )
[ ] -3518 years-Before surgery Testosterone isobutyrate Sex reassignment surgery (hysterectomy, ovariectomy, and bilateral mastectomy) After surgery Testosterone isobutyrate 25 mg intramuscular every week, OR Testosterone propionate 250 mg every third week intramuscular OR Testosterone undecanoate 40 mg 4 times day.Dual-energy X-ray absorptiometry (DXA); BMD at the lumbar spine and femoral neckF to MMale controlsLumbar spine 1.213 ± 0.15BMD after adequate dose of testosterone therapy is higher after 18 years of testosterone administration BMD at the spine its similar to baseline after 18 years of testosterone administration. Androgens compensate for the low estrogen level in the bone metabolism
Lumbar spine 1.203 ± 0.065
Femoral neck 1.192 ± 0.19
Female controlsFemoral neck 0.950 ± 0.11
Lumbar spine 1.192 ± 0.19
Femoral neck 0.822 ± 0.09
Summary of FindingsM to F 921F to M 719Time Receiving the Treatment (Range) >3 years to 18 yearsM to F Hormone Therapy Cyproterone Acetate (Antiandrogen) EstrogensF to M Hormone Therapy TestosteroneBMD Method of Evaluation Conventional whole-body scanner; Dual-energy X-ray absorptiometry (DXA)--BMD Contradictory results, the BMD was preserved or increased in 788 M to F patients (82.66%); BMD decreased in 73 M to F patients (8.47%); BMD Increased in 35 F to M patients (4.93%); BMD preserved in 674 F to M patients (95.06%)

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.

Author and Year of PublicationSampleBone Metabolism Markers
M to FF to MCalcium (mmol/L) or (mg/dL)Phosphate (mmol/L)Alkaline phosphatase (U/L)Osteocalcin (µg/L) or (ng/mL)
Before or ControlsAfter or TestsBefore or ControlsAfter or TestsBefore or ControlsAfter or TestsBefore or ControlsAfter or Tests
Schlatterer K et al. 1998 [ ]1010M to FNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluated
F to MNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluated
Sosa M et al. 2003 [ ]53-M to F9.4 ± 0.520 mg/dL9.156 ± 0.564 mg/dL3.348 ± 0.457 mg/dL3.16 ± 0.619 (mg/dL)Not evaluatedNot evaluatedNot evaluatedNot evaluated
Ruetsche AG et al. 2005 [ ]2415M to F2.10–2.55 mmol/L2.33 ± 0.08 (2.18–2.53) mmol/L0.74–1.55 mmol/L1.15 ± 0.12 (0.76–1.49) (mmol/L)36–108 (μkat/L)63 ± 15 (32–159) (μkat/L)2.3–13.8 (ng/mL)5.0 ± 1.0 (2.3–9.1) (ng/mL)
F to M2.10–2.55 mmol/L2.38 ± 0.02 (2.32–2.52) mmol/L0.74–1.55 mmol/L1.05 ± 0.08 (0.69–1.23) (mmol/L)36–120 (μkat/L)6.3 ± 1.5 (3.4–11.4) (μkat/L)1.2–10.5 (ng/mL)6.3 ± 1.5 (3.4–11.4) (ng/mL)
Lapauw B et al. 2008 [ ]23-M to FNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluated
T’Sjoen G et al. 2009 [ ]50 M to FNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluated
Van Caenegem, et al. 2012 [ ]-66F to MNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluated
Wierckx K et al. 2012 [ ]5050T to FNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluated
F to MNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluated
Wiepjes C et al. 2018 [ ]711543M to FNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluated
F to MNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluatedNot evaluated
Broulik PD et al. 2018 [ ]-35F to MNot evaluatedNot evaluatedNot evaluatedNot evaluatedFemale controls 1.51 ± 0.10 (μkat/L)1.48 ± 0.12 (μkat/L)Female controls 24.05 ± 6.8 (µg/L)22.04 ± 7.92 (µg/L)
Male controls 1.39 ± 0.14 (μkat/L)Male controls 23.5 ± 8.0 (µg/L)

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.

Author and Year of PublicationSampleBone Turnover Markers
M to FF to MSerum Procollagen Type I N-Terminal Propeptide (P1NP) Formation (ng/mL)Serum Collagen type I Crosslinked C-Telopeptide (CTX) Resorption (ng/mL)
Before or ControlsAfter or TestsBefore or ControlsAfter or Tests
Schlatterer K et al. 1998 [ ]1010M to FM to FNot evaluatedNot evaluatedNot evaluated
F to MF to MNot evaluatedNot evaluatedNot evaluated
Sosa M et al. 2003 [ ]53-M to FNot evaluatedNot evaluatedNot evaluatedNot evaluated
Ruetsche AG et al. 2005 [ ]2415M to FNot evaluatedNot evaluatedNot evaluatedNot evaluated
F to MNot evaluatedNot evaluatedNot evaluatedNot evaluated
Lapauw B et al. 2008 [ ]23-M to F32 [ , , , , , , , , , , , , , , , , , , , , , ] (46 controls)49 [ , , , , , , , , , , , , , , , , , , , , , , , , , , ] (23 patients)0.36 ± 0.16 (46 controls)0.24 ± 0.14 (23 patients)
T’Sjoen G et al. 2009 [ ]50-M to FLumbar spine 36.6 ± 22.6Lumbar spine 45.2 ± 24.40.31 ± 0.200.32 ± 0.23
Van Caenegem, et al. 2012 [ ]-66F to M Before Surgery40 ± 1250 ± 240.20 ± 0.100.36 ± 0.15
Wierckx K et al. 2012 [ ]5050M to F102 ng/mL106–125 (ng/mL) (2 patients, all the others were within normal ranges)<0.58 (ng/dL)0.62–1.24 (ng/dL) (4 patients, all the others were within normal ranges)
F to MNormal rangeNormal rangeNormal rangeNormal range
Wiepjes C et al. 2018 [ ]711543M to FNot evaluatedNot evaluatedNot evaluatedNot evaluated
F to MNot evaluatedNot evaluatedNot evaluatedNot evaluated
Broulik PD et al. 2018 [ ]-35F to MNot evaluatedNot evaluatedControl Female 400 ± 124302 ± 190
Control Male 390 ± 140

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 ).

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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 ).

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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.

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

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Which is the best surgical approach for female-to-male sexual reassignment a systematic review of hysterectomy and salpingo-oophorectomy options from the gynecological perspective.

gender reassignment hormone therapy female to male

1. Introduction

2. materials and methods, 2.1. research strategy, 2.2. selection criteria for full-text article review, 2.3. outcome measures, 2.4. risk of bias, 2.5. data collection, 2.6. novel surgical techniques, 2.7. statistical analysis, 3.1. population, 3.2. intervention, 3.3. comparison, 3.4. outcomes, 4. discussion, limitations and strengths, 5. conclusions, supplementary materials, author contributions, institutional review board statement, informed consent statement, data availability statement, conflicts of interest.

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Click here to enlarge figure

QueryPopulationInterventionComparisonOutcomes
1female-to-maleHysterectomy and salpingo-oophorectomynonev-NOTES/vaginal surgery reduces operative time
2female-to-maleHysterectomy and salpingo-oophorectomynoneLaparoscopic/robotic surgery reduce operative time
3female-to-maleHysterectomy and salpingo-oophorectomynonev-NOTES/vaginal surgery reduces intra and postoperative complications
4female-to-maleHysterectomy and salpingo-oophorectomynoneLaparoscopic/robotic surgery reduces intra- and postoperative complications
5female-to-maleHysterectomy and salpingo-oophorectomynonev-NOTES/vaginal surgery reduces postoperative pain
6female-to-maleHysterectomy and salpingo-oophorectomynoneLaparoscopic/robotic surgery reduces postoperative pain
7female-to-maleHysterectomy and salpingo-oophorectomynonev-NOTES/vaginal surgery reduces hospital stay
8female-to maleHysterectomy and salpingo-oophorectomynoneLaparoscopic/robotic surgery reduces hospital stay
Study and YearOrigin of Study Patients
Enrolled
Age
(Mean ± SD)
BMI
(Mean ± SD)
Parity
(N, %)
Uterine Weight
(Mean ± SD) g
Bogliolo et al., 2014 [ ]Italy10 TM28 ± 5.722 ± 1.70Not reported
Gardella et al., 2021
[ ]
Italy60 TM30.62 ± 7.9323.52 ± 4.26 0Nor reported
Giampaolino et al., 2021
[ ]
Italy20 TMMedian: 23.5 (19.5–28.4)Median: 22.5 (range: 21–24.7) Not reported
Obedin-Maliver, 2017
[ ]
USA33 TM35.2 ± 69.927.9 ± 65.42 (6.1) Not reported
Jeftovic et al., 2018
[ ]
Serbia124 TMNot reportedNot reported Not reportedNot reported
O’Hanlan et al., 2007
[ ]
USA 31.76 ± 7.427.36 ± 5.82 (4.9)118.02 ± 115.6
Donmez et al., 2024
[ ]
Turkey83 TMv-NOTES: 27.57 ± 3.9
TLH: 26.6 ± 4.8
v-NOTES: 22.9 ± 2.8
TLH: 24.8 ± 4.4
Not reportedNot reported
Lee et al., 2018
[ ]
Taiwan56 TMVH: 29.3 ± 6.4
v-NOTES: 28.8 ± 7.3
VH: 23.7 ± 4.4
v-NOTES: 24.3 ± 5.0
VH:0
v-NOTES:0
VH: not reported
v-NOTES: not reported
Study and YearStudy
Design
Patients
Enrolled
ProcedureOperative TimeBlood Loss,
mL
Hospital Stay, DaysVisual
Analog Scale (VAS)
Intra- and
Postoperative Complications, n (%)
Bogliolo et al., 2014 [ ]Retrospective study10 TMRSSH and mean ± SD minutes
BSO
Mean ± SD minutes
Operative time: 137 ± 32.
Console time:79 ± 15.
Docking time: 9 ± 2 m.
Mean ± SD 30 ± 24 mLMean ± SD days
2.4 ± 0.9
Mean
VAS: 1 (interquartile 0–3 at 1 h after surgery)
VAS: 0 (interquartile 0–0) at 24 h after surgery
1 (10)
Gardella et al., 2021
[ ]
Prospective monocentric study60 TMRSSH and BSOMean ± SD
Total surgical time: 143.77 ± 40.39.
Console time: 100.73 ± 32.26.
Docking time: 7.72 ± 2.61.
Hb drop mean ± SD: 1.1 ± 0.463.85 ± 1.26Mean ± SD
VAS: 4.53 ± 1.73 at 1 h after surgery
VAS: 2.35 ± 1.96
3 (4.83)
Giampaolino et al., 2021
[ ]
Single-center retrospective study20 TMRH and BSOMedian
Operation time: 90 (interquartile 65–150).
Docking time: 15 (interquartile 10–25) minutes.
Time spent in the operating room: 140 (90–180).
Median
90 (interquartile 150–30) mL
Decrease in hemoglobin levels (%): 8 (4–16)
Median
2.5 (interquartile 2–4)
Median
VAS: 5 (interquartile 3–8) score in the immediate postoperative period.
VAS: 3 (interquartile 1–6) at 24 h after surgery.
VAS: 2 (interquartile 0–5) at 28 h after surgery.
Not reported
Obedin-Maliver, 2017
[ ]
Single-center retrospective cohort study33 TM14 TM: TLH and 13 BSO (one subject only adnexal surgery).
8 TM: VH and BSO.
11 TM: AH and BSO.
Not reported Median
TLH and BSO:175 (interquartile 110–30).
VH and BSO: 250 (interquartile 175–400).
AH and BSO: 225 (interquartile 200–250).
Not reportedNot reported9 (27.3)
Jeftovic et al., 2018
[ ]
Retrospective study124 TM92 TM: VH and BSO
32 TM: TLH and BSO
Mean
VH:51 (interquartile 46–72)
TLH: 76 (interquartile 68–90)
Not reportedMean
VH: 4 (interquartile 3–6)
TLH 4 (interquartile 3–6)
Not reportedVH: 1 (1%)
TLH: 1 (3%)
O’Hanlan et al., 2007
[ ]
Retrospective study41 TMTHL and BSOMean ± SD
74.08 ± 35.4
Mean ± SD
26.88 ± 27.7
Mean ± SD
1.07 ± 0.3
Not reported5 (12.2)
Donmez et al., 2024
[ ]
Retrospective cohort study 83 TM21 TM: v-NOTES and BSO
62 TM: TLH and BSO
mean ± SD:
v-NOTES: 126.1 ± 37.9
TLH: 76.1 ± 33.9
Hemoglobin drop, mean ± SD
v-NOTES: 1.5 ± 0.9
In TLH: 1.5 ± 0.9 (0.1–3.4)
Postoperative hospital stay, days:
v-NOTES: 1.6 ± 1.01
TLH: 2.9 ± 0.5
Postoperative pain second hour after surgery, median ± SD
v-NOTES: 5 ± 1.56
TLH: 8 ± 1.11
Postoperative 24th hour after surgery, median ± SD
TVNH: 1 ± 0.62
TLH: 2 ± 0.9
0
Lee et al., 2018
[ ]
Retrospective study56 TM42 TM: VH and BSO
14: v-NOTES and BSO
mean ± SD:
v-NOTES: 144.3 ± 51.7
VH: 149.2 ± 47.1
median
v-NOTES: 200 (interquartile 100–388)
VH:150 mL (interquartile 100–350)
mean ± SD
v-NOTES: 7.7 ± 2.4
VH: 7.1 ± 3.1
VAS at 2 h and 72 h, mean ± SD:
v-NOTES:
4.9 ± 3.0 and 1.7 ± 1.0 (n = 12)
VH: 7.1 ± 1.4 (n = 42) and 2.7 ± 1.1 (n = 34)
v-NOTES 1 (0.025)
VH: 5 (11.9)
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Share and Cite

Dominoni, M.; Gritti, A.; Pano, M.R.; Sandullo, L.; Papa, R.; Torella, M.; Gardella, B. Which Is the Best Surgical Approach for Female-to-Male Sexual Reassignment? A Systematic Review of Hysterectomy and Salpingo-Oophorectomy Options from the Gynecological Perspective. Medicina 2024 , 60 , 1095. https://doi.org/10.3390/medicina60071095

Dominoni M, Gritti A, Pano MR, Sandullo L, Papa R, Torella M, Gardella B. Which Is the Best Surgical Approach for Female-to-Male Sexual Reassignment? A Systematic Review of Hysterectomy and Salpingo-Oophorectomy Options from the Gynecological Perspective. Medicina . 2024; 60(7):1095. https://doi.org/10.3390/medicina60071095

Dominoni, Mattia, Andrea Gritti, Martina Rita Pano, Lucia Sandullo, Rossella Papa, Marco Torella, and Barbara Gardella. 2024. "Which Is the Best Surgical Approach for Female-to-Male Sexual Reassignment? A Systematic Review of Hysterectomy and Salpingo-Oophorectomy Options from the Gynecological Perspective" Medicina 60, no. 7: 1095. https://doi.org/10.3390/medicina60071095

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Owner Explains Why Her Male Cat Had ‘Gender Reassignment Surgery’

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Owner Explains Why Her Male Cat Had ‘Gender Reassignment Surgery’

A pet owner has gained viral attention after revealing the procedure her cat had that is often likened to human gender-reassignment surgery.

In a video shared on June 5 on TikTok , which has received more than 1.3 million views, Charlie Chronis from Los Angeles shared footage of her cat Siegfried, joking that he had “gender reassignment surgery.”

“[It is] funny that it’s garnered so much attention—it’s honestly a pretty common surgery for male cats,” Chronis told Newsweek . The Siamese mixed-breed cat underwent a perineal ureterostomy, often abbreviated as PU surgery, which is a solution for cats with a blockage in their urinary tract. The surgery creates a new urinary opening, decreasing the length of the urethra and allowing urine to bypass this narrowed region.

The surgery is often recommended when a urethral obstruction within the penis cannot be removed through medical therapy, and in cases of recurrent urethral obstructions. For many male cats, this surgery can be lifesaving, allowing them to live healthier, more comfortable lives.

“He had kidney stones , which led to persistent urinary tract infections and, after treating him with a catheter three times, this was the final solution,” Chronis said.

In serious cases, urinary blockages in cats can prevent them from urinating completely. Life-threatening consequences can occur in as little as 12 to 24 hours of being unable to urinate, and death from untreated obstruction may occur in 36 to 48 hours.

Thanks to the PU surgery, which makes the male cat’s urethra more similar to a female’s, the risk of future blockages will be reduced.

A month and a half after his operation, Siegfried is back to his normal, playful self. “I thought my situation was hilarious and unimaginable, leading me to post my video,” said Chronis. “[I] didn’t realize how many other cats have gone through a similar experience.”

The video prompted lots of responses online from people who were amazed to learn about the procedure.

BrightBlueEyes posted, “I never knew this was a thing,” while Mary wrote: “We adopted a cat like this and named him RuPawl.”

“I’ve got a trans kitty too!” commented Ginabutcherr.

Someone who sees the procedure often weighed in too, as A_scho posted: “Vet tech here… This is hilarious.”

RecklessRoca wrote: “Omg [oh my God] I know someone whose cat had this and we thought it was a one-time deal.”

Do you have funny and adorable videos or pictures of your pet you want to share? Send them to [email protected] with some details about your best friend, and they could appear in our Pet of the Week lineup.

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The post Owner Explains Why Her Male Cat Had ‘Gender Reassignment Surgery’ appeared first on Newsweek .

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  • DOI: 10.1186/s13058-024-01867-w
  • Corpus ID: 270923199

Effect of testosterone therapy on breast tissue composition and mammographic breast density in trans masculine individuals

  • Y. Heng , Gabrielle M. Baker , +15 authors Gerburg M Wulf
  • Published in Breast Cancer Research 2 July 2024

44 References

Deep learning image analysis of benign breast disease to identify subsequent risk of breast cancer.

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Associations of alcohol consumption with breast tissue composition

Revisiting androgen receptor signaling in breast cancer, toker cell hyperplasia in the nipple-areolar complex of transmasculine individuals., breast cancer incidence reduction in women treated with subcutaneous testosterone: testosterone therapy and breast cancer incidence study., early-life and adult adiposity, adult height, and benign breast tissue composition, testosterone therapy and breast histopathological features in transgender individuals, associations of reproductive breast cancer risk factors with breast tissue composition, evaluation of libra software for fully automated mammographic density assessment in breast cancer risk prediction., pathologic evaluation of breast tissue from transmasculine individuals undergoing gender-affirming chest masculinization., related papers.

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Hormone therapy in female-to-male transgender patients: searching for a lifelong balance

Affiliations.

  • 1 Department Interdisciplinary Medicine, Unit of Obstetrics and Gynecology, University of Bari "Aldo Moro", Bari, Italy.
  • 2 Interdisciplinary Department of Medicine, Gynecology and Ostetrics Clinic, University of Bary, Bari, Italy. [email protected].
  • 3 Department of Obstetrics and Gynaecology, ASTT Lecco, Ospedale Leopoldo Mandic, Merate, Italy.
  • 4 Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, CNR, Bari, Italy.
  • PMID: 33026609
  • DOI: 10.1007/s42000-020-00238-2

Background: Reassignment of a female-to-male (FtM) person requires gender-affirming, androgenic hormonal treatment that is planned to induce appropriate structural changes. This therapy must be prolonged long term, even after the sex reassignment surgery (SRS). The purpose of this study is to evaluate the effects of hormone therapy with testosterone in FtM subjects during a 24-month follow-up in order to highlight the occasional need for early decompensation and to make adequate hormone therapy modulations.

Methods: Fifteen out of 23 FtM persons had been previously treated with SRS, while eight were still awaiting surgery. During hormone therapy, both groups were followed for 24 months, with evaluation of desired changes, adverse effects, and functional or metabolic indicators.

Results: In the group of operated FtM subjects (15/23), a significant increase of total testosterone (total T) and free testosterone (free T) was found after 24 months. Luteinizing hormone (LH) maintained a low level, decreasing after ovariectomy, while FSH increased. Voice deepening, facial and body hair variation, male-pattern balding, and body mass index (BMI) increase are all physical changes due to androgenization. In both groups of patients who have been closely monitored, the side effects and thromboembolic, metabolic, and cardiovascular risks of androgen therapy, even in the long term, appear to be irrelevant.

Conclusion: Total T, free T, and LH dosages are shown to be reliable markers of correct androgenization. Strict monitoring of lipid profile, evaluation of BMI and hematocrit, avoidance of self-initiated therapeutic modifications, adherence to a healthy lifestyle, and avoidance of excessive daily calorie intake can limit risks linked to long-term testosterone administration.

Trial registration: Retrospectively registered.

Keywords: Health; Long-term therapy; Testosterone; Transgender.

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Cuba’s first transgender athlete shows the progress and challenges faced by LGBTQ people

At 26-years-old, Ely Malik Reyes has made history as the first transgender athlete to officially compete in a Cuban sports league. (AP/ Ariel Fernández and Milexsy Durán)

Image

Transgender Cuban athlete Ely Malik Reyes, who practices mixed martial arts known as sanda, trains at a gym in Regla, across the bay from Havana, Cuba, Tuesday, June 11, 2024. Reyes became the first trans athlete to officially compete in a Cuban league. (AP Photo/Ariel Ley)

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Transgender Cuban athlete Ely Malik Reyes, right, who practices mixed martial arts known as sanda, spars with fellow athlete Leandro Matos at a gym in Regla, across the bay from Havana, Cuba, Tuesday, June 11, 2024. Reyes became the first trans athlete to officially compete in a Cuban league. (AP Photo/Ariel Ley)

Transgender Cuban athlete Ely Malik Reyes, who practices mixed martial arts known as sanda, rests during a workout at a gym in Regla, across the bay from Havana, Cuba, Tuesday, June 11, 2024. Reyes became the first trans athlete to officially compete in a Cuban league. (AP Photo/Ariel Ley)

HAVANA (AP) — Ely Malik Reyes stepped onto the cordless platform and began delivering powerful punches and spectacular flying kicks against his combatant. He lost the fight, but won a major victory that day by becoming the first transgender athlete to officially compete in a Cuban sports league.

Reyes, a 26-year-old transgender man, competed for the first time in the male 60/65-kilogram (132/143-pound) category of sanda, a demanding contact sport that blends martial arts like kung fu with kickboxing.

The June 1 milestone marked the latest step toward inclusion in Cuba, one of Latin America’s most progressive countries when it comes to LGBTQ rights. Yet, Reyes himself acknowledges having to overcome challenges, including the lack of medications, a law that sets conditions to change his gender on his ID and the “suspicious looks” he sometimes gets from people in the street.

“Educating society doesn’t happen in two days,” he said.

Reyes, who lives with his girlfriend in a colorful house on the outskirts of Havana, supports himself by repairing air conditioners, as his sanda fights are unpaid. He has been on hormone therapy for two years, but says he does not want full genital reassignment surgery.

Image

His transition has been far from easy.

It began over four years ago when he visited Cuba’s Center for Sexual Education and consulted with a psychologist. He then saw endocrinologists and underwent tests to obtain a “tarjetón,” a special card that allows Cubans to purchase medication at pharmacies, enabling him to get the hormones needed for his transition.

But as Cuba’s economic crisis deepened , medications became scarce so he had to rely on other people who brought testosterone from abroad. While not illegal, the practice can be very expensive. “I’m an athlete; I can’t neglect my hormone treatment. ... I have to stay on top of it,” he said.

Changing his identity in official documents posed yet another challenge. While Reyes was able to legally change his name last year, his ID card still displays an “F” for female. That is because Cuba’s current law requires full genital reassignment surgery for this change — something he does not want to do.

LGTBQ activists in Cuba say a solution could come soon through a new Civil Registry law currently being drafted in the National Assembly that would allow people to change their gender on their ID cards — or eliminate this requirement altogether.

The changes stem from Cuba’s 2019 constitution , which gave way to the 2022 Family Code that allowed same-sex couples to marry and adopt as well as surrogacy pregnancies among other rights. Though approved via referendum by a large majority , the measure faced opposition from evangelical groups and other conservative groups that disagreed with its provisions.

While Reyes’s ID still formally identifies him as female, sports authorities accepted his male status based on his hormone treatments, medical reports and self-identification. This allowed him to compete in the male category of the Cuban Fighters League.

“It’s something new; it’s a challenge that I have embraced with much love,” said Reyes’s coach, Frank Cazón Cárdenas, the president of Cuba’s sanda community who handled the athlete’s registration.

Cazón said he had to work on two fronts to make it happen: discussing Reyes with the other sanda male team members — and securing approval from the powerful Cuban Sports Institute, which ultimately authorized Reyes to participate in the male category.

Cuba’s LGBTQ community celebrated Reyes’s milestone, noting it was the result of a hard-fought battle.

“It was only a matter of time,” said Francisco “Paquito” Rodríguez Cruz, a well-known LGBTQ rights activist in Cuba, referring to the sports institute’s unprecedented greenlight for a transgender athlete to take part in an official competition. “It’s the logical consequence of what has been done in the last 15 or 20 years.”

“It’s obviously a cultural process of change that is still controversial,” Rodríguez said.

Follow AP’s coverage of Latin America and the Caribbean at https://apnews.com/hub/latin-america

gender reassignment hormone therapy female to male

Transgender prisoners sue Idaho, want state to pay for gender-change procedures

by RAY LEWIS | The National Desk

 Idaho Gov. Brad Little (Getty Images) and a Pride flag (AP Photo)

BOISE, Idaho (TND) — Three imprisoned transgender women sued Idaho officials on Friday over a law allegedly preventing them from receiving state-funded gender-change procedures.

The women, referred to as Jane Roe, Jane Poe and Jane Doe in the lawsuit, accuse Idaho Gov. Brad Little, Attorney General Raúl Labrador and Department of Corrections officials of inflicting cruel and unusual punishment by enforcing a law that blocks public funds for gender transition procedures.

Idaho's House Bill 668 prevented the three individuals, along with other imprisoned people, from undergoing gender-change procedures beginning on Monday, according to the lawsuit. They all have allegedly received such treatments for several years and argue the officials are violating the Eighth Amendment by cutting them off.

Roe claims she will experience irreversible damage to the feminization she has undergone, along with an “extreme” hormone imbalance that will psychologically impact her. She has received hormone therapy from the Idaho Department of Corrections to treat gender dysphoria since 2015, according to the lawsuit, which was filed by the American Civil Liberties Union.

Ms. Roe’s hormone therapy has given her hope for a better life and a better future,” the lawsuit reads. “It has reduced her clinical symptoms of gender dysphoria.”

Poe has also expressed concern over how the law will impact her well-being. She allegedly had a lapse in hormone therapy last year and experienced male puberty and increased dysphoria. Poe was mentally unstable, more depressed and anxious as a result, according to the lawsuit.

“She does not want to suffer this again,” the lawsuit reads. “She fears she would suffer the same suicidality and severe mental pain and suffering as she did before.”

Doe claims hormone therapy has resulted in decreased anxiety and improved quality of life. When she was first arrested last year, she did not receive any therapy, and her breast tissue allegedly reduced while her testicles dropped.

Ms. Doe is concerned about how this will impact her,” the lawsuit reads. “If she is not able to continue her prescribed hormone replacement therapy, she fears her gender dysphoria and subsequent depression will get worse.”

Gov. Little did not return The National Desk’s request for comment. Attorney General Labrador declined to comment.

The governor has previously criticized using public funds for gender-change procedures. In a May letter to the state's Department of Health and Welfare, he reportedly opposed using Medicaid funds for hormone therapy.

“Hardworking taxpayers should not be forced to pay for an adult’s sex reassignment surgery,” Gov. Little wrote.

Have questions, concerns or tips? Send them to Ray at [email protected].

gender reassignment hormone therapy female to male

  • Olympics 2024

What to Know About Nikki Hiltz and the History of Trans and Nonbinary Olympians

Nikki Hiltz reacts after winning in the women's 1500-meter final on Day Ten of the 2024 U.S. Olympic Team Track & Field Trials at Hayward Field on June 30, 2024 in Eugene, Ore.

Nikki Hiltz doesn’t just represent the U.S. on the race track.

“This is bigger than just me,” the 29-year-old from California told NBC after qualifying for the Olympics on June 30 after running 1500 meters in 3 minutes and 55.33 seconds, a personal best and a meet record in the women’s event. “It’s the last day of Pride Month, and I wanted to run this one for my community. All the LGBTQ folks, you guys brought me home that last hundred. I could just feel the love and support.”

Hiltz, who identifies as transgender and nonbinary and uses they/them pronouns, already holds  the American record for the women’s outdoor mile. They are now set to make more history next month as one of only a few gender nonconforming athletes ever to compete at the Olympics.

View this post on Instagram A post shared by Nikki Hiltz (@nikkihiltz)

In 2021, New Zealand weightlifter Laurel Hubbard took part in the Tokyo Games, becoming at age 43 one of the world’s first openly trans Olympians. Facing controversy over her alleged biological advantages over female-born competitors, despite suppressing her testosterone levels below a certain threshold, Hubbard failed to medal .

In the same Games, mononymous soccer player Quinn became the first trans-identifying person to win an Olympic medal, taking home gold with Canada’s women’s team. (Quinn had earned a bronze medal in 2016 but only came out as nonbinary in 2020.) They will be vying for another medal in Paris this summer.

BMX rider Chelsea Wolfe also made history that same year, becoming the first openly trans athlete to join the roster of Team USA, after she qualified as an alternate, though she ultimately didn’t compete in Tokyo.

Skateboarder Alana Smith , who identifies as nonbinary, did compete in Tokyo for Team USA, at one point holding up their skateboard with their preferred pronouns “they/them” scribbled on it. Though they didn’t medal, they said they accomplished their goal at the Olympics, which was “to be happy and be a visual representation for humans like me.”

In 2022, American figure skater Timothy LeDuc became the first openly nonbinary Olympian to compete in the Winter Games in Beijing, where they placed 8th in the pairs category alongside their partner Ashley Cain-Gribble. “I know for me, people who are non-binary, it’s only possible because amazing queer people have come before me and laid the groundwork for me,” LeDuc said at the time. “And so now I want to do that for others to come after as well.”

Read More: Your Guide to the Paris 2024 Summer Olympics: When and How to Watch—and What to Expect

Sports has long grappled with issues of sex and gender identity, as many critics of inclusivity have argued about potential unfairness. Most competitive individual and team events are also organized around binary sex and gender categories.

In 2004 , the International Olympic Committee (IOC) first opened its Games to transgender individuals under certain conditions, including undergoing hormone therapy and gender-affirming surgery. The surgery requirement was removed in 2016 to reflect more modern attitudes, but male-to-female transgender athletes were still required to meet certain testosterone levels for a year before they could compete. In 2021, the IOC updated its policies again to allow each sport’s governing body to determine its own rules for the participation of trans and nonbinary athletes. 

Since then, global governing bodies for athletics , boxing , cricket , cycling , and swimming , among others, have tightened their rules on trans athletes, particularly trans women who were assigned male at birth.

But as more people open up to the notion of gender as a spectrum , especially with younger generations increasingly identifying as nonbinary, athletes like Hiltz, who was assigned female at birth and has always competed in women’s events, are showing opponents that it’s not so easy to politicize the issue.

After a social media user accused Hiltz of being “a mediocre man stealing a woman’s place on the Olympic team,” Hiltz responded with a laughing emoji and said to search what nonbinary means.

The “wE cAn aLwAys TeLL” crowd at it again 😂 Ted how bout you go touch some grass and then type into google “what does nonbinary mean?” https://t.co/hyJDnBASMZ — Nikki Hiltz (@Nikki_Hiltz) July 3, 2024

“I knew an Olympic birth would bring tremendous amount of online love and support but also knew the massive platform would bring in some hate and ignorance as well,” Hiltz later added on Instagram. “Throughout this journey to the Paris Olympic Games I’m going to continue to use my platform to uplift trans and queer folks and maybe educate some people along the way too. If you consider yourself an ally to the LGBTQ+ community I hope you join me in doing the same.”

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Transgender runner Nikki Hiltz is headed to the Paris Olympics

Nikki Hiltz celebrates after crossing the finish line on the track

Transgender and nonbinary middle-distance runner Nikki Hiltz ran the second fastest time ever of any American in the women’s 1500-meter race at the U.S. Olympic Trials Sunday, qualifying for the 2024 Olympic Games in Paris. 

Hiltz, who uses they/them pronouns, charged ahead of Elle St. Pierre and Emily Mackay in the final stretch of the race, finishing with a time of 3:55:33, a trials record. All of the top eight finishers set a new personal best time, according to OutSports. Paris will mark Hiltz’s Olympic debut. 

In a post-race interview with NBC Sports , Hiltz, 29, said the race had significance beyond their personal accomplishment. 

“This is bigger than just me. It’s the last day of Pride Month . ... I wanted to run this one for my community,” they said. “All the LGBT folks, yeah, you guys brought me home that last hundred [meters]. I could just feel the love and support.”

Hiltz said Elle St. Pierre, who finished third and was the top-finishing American in the Tokyo Olympics women’s 1500, pushed them and the other runners to go faster. St. Pierre was in the lead for most of the race, finishing the first lap in 61 seconds.

“Elle St. Pierre has elevated women’s distance running. I saw the time, and I didn’t think that was possible,” Hiltz told NBC Sports. “We all had to rise because of her. … Awesome team we’re sending to Paris.”

Pierre and the second-place finisher, Emily Mackay, also qualified for the Paris Olympics Sunday.

Hiltz wrote in a social media post Monday that a childhood dream of theirs came true when they qualified for the Paris Olympics. 

“I’m not sure when this will fully sink in,” they wrote. “All I know is today I’m waking up just so grateful for my people, overwhelmed by all the love and support, and filled with joy that I get to race people I deeply love and respect around a track for a living.”

The International Olympic Committee  updated its rules regarding  transgender athletes in 2021 to defer to each sport’s governing body.

World Athletics, which oversees international track and field competition,  adopted a policy last year that bars  all trans women athletes who went through male puberty from competing in female track and field categories. Trans men are allowed to compete in male categories if they have satisfactory signed declarations of their gender identities.

World Athletics’ policy doesn’t specifically mention athletes who are nonbinary, meaning those who identify as neither exclusively male nor exclusively female. However, nonbinary competitors who were assigned female at birth are generally allowed to compete in female categories if they haven’t received hormone therapy.

Hiltz won’t be the first nonbinary athlete to participate in the Olympics. Canadian soccer star Quinn became the first openly transgender and nonbinary athlete to participate in the Olympics in Tokyo in 2022. They went on to become the first transgender athlete to win a medal at the Olympics when Canada beat Sweden 3-2 in penalty kicks. 

Quinn was among at least 186 out LGBTQ athletes who competed at the Tokyo Games, according to OutSports. Hiltz hasn’t been the only LGBTQ athlete to qualify for the Paris Olympics so far. Timo Cavelius of Germany will be the first out gay man to compete in Olympic judo, according to OutSports.

Related stories:

  • Simone Biles qualifies for her third Olympics as Hezly Rivera snags fifth spot on the team
  • Eight years ago she didn't know how to clip into a bike — now she's an Olympic cyclist
  • Explainer: What does nonbinary mean?

For more from NBC Out, sign up for our weekly newsletter.

gender reassignment hormone therapy female to male

Jo Yurcaba is a reporter for NBC Out.

Olympics

Nikki Hiltz, transgender, nonbinary runner, qualifies for Olympics: ‘This is bigger than just me’

EUGENE, OREGON - JUNE 30: Nikki Hiltz reacts after winning in the women&#039;s 1500 meter final on Day Ten of the 2024 U.S. Olympic Team Track &amp;amp; Field Trials at Hayward Field on June 30, 2024 in Eugene, Oregon. (Photo by Christian Petersen/Getty Images)

The biggest race of Nikki Hiltz’s career is coming soon, but the middle-distance runner who identifies as transgender and nonbinary said that racing to a spot on the U.S. Olympic team held a special significance because it came at the end of Pride Month.

Hiltz, 29, whose sex was assigned as female at birth, earned a ticket to the Paris Games with a meet-record time of 3:55.33 in the women’s 1500-meter final of the U.S. Olympic trials on June 30. The performance easily beat the previous Olympic trials record, which was 3:58.03 set by Elle St. Pierre at the 2021 U.S. track and field trials. St. Pierre finished third on Sunday to also earn a spot on Team USA along with the second-place finisher, Emily Mackay.

“This is bigger than just me,” Hiltz told NBC. “It’s the last day of Pride Month, and I wanted to run this one for my community. All the LGBTQ folks, you guys brought me home that last 100. I could just feel the love and support.”

A down to the wire finish in the 1500m results in an Olympic Trials record for Nikki Hiltz! 🤯 #TrackFieldTrials24 pic.twitter.com/FlkjDZj4uh — NBC Olympics & Paralympics (@NBCOlympics) July 1, 2024

Runners like Hiltz who were assigned female at birth do not face the same restrictions for women’s divisions as transgender athletes who were assigned male at birth.

Many sports have grappled in recent years with questions about gender and sex. The governing body for the Olympics updated its policies in 2021 and defers to each sport’s governing body for rules on participation.

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Track and field’s governing body, World Athletics, adopted new rules last year, effectively barring athletes who have transitioned from male to female and have gone through male puberty from competing in women’s divisions. If the athlete was assigned female at birth, they are generally allowed to compete in women’s categories if they haven’t received hormone therapy.

Hiltz wrote a piece for Runner’s World in 2021 explaining how the sport helped them express their gender identity and find descriptive terms  that felt authentic. “I’m transgender, I don’t identify with the sex I was assigned at birth, I currently describe my gender as non-binary, and I prefer they/them pronouns,” they wrote.

Hiltz has the hardware to prove they will be in the mix for a medal at the Olympics, boasting a silver from the World Athletics Indoor Championships in March.  Two-time Olympic gold medalist Faith Kipyegon is the favorite in the 1500m as she looks to defend her title. 

Before cruising to the Olympic trials 1500-meter record, Hiltz also posted an American record time in the women’s mile back in July 2023 with a 4:16.23 run at Herculis, a Diamond League meet in Monaco.

The first round of the women’s 1500-meter race at the Olympics begins Aug. 6 at 4:05 a.m. ET. The semifinal is Aug. 8 at 12:35 p.m., and the final is Aug. 10 at 1:25 p.m.

(Photo: Christian Petersen / Getty Images)

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Tess DeMeyer is a Staff Editor for The Athletic working on the live/breaking news team. Prior to joining The Athletic, she worked as an associate digital producer at Sports Illustrated. Tess attended Brown University and originates from a small town outside of Savannah, GA. Follow Tess on Twitter @ tess_demeyer

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  4. Overview of feminizing hormone therapy

    Asscheman H, T'Sjoen G, Lemaire A, Mas M, Meriggiola MC, Mueller A, et al. Venous thrombo-embolism as a complication of cross-sex hormone treatment of male-to-female transsexual subjects: a review. Andrologia. 2014 Sep;46(7):791-5. Brighouse D. Hormone replacement therapy (HRT) and anaesthesia. Br J Anaesth. 2001 May 1;86(5):709

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  8. Overview of gender-affirming treatments and procedures

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  14. Hormone therapy in female-to-male transgender patients: searching for a

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  23. Effect of testosterone therapy on breast tissue composition and

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  24. Hormone therapy in female-to-male transgender patients: searching for a

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  26. Overview of masculinizing hormone therapy

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  27. Transgender prisoners sue Idaho, want state to pay for gender ...

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  28. Nikki Hiltz and the History of Trans and Nonbinary Olympians

    In 2004, the International Olympic Committee (IOC) first opened its Games to transgender individuals under certain conditions, including undergoing hormone therapy and gender-affirming surgery.

  29. Transgender runner Nikki Hiltz is headed to the Paris Olympics

    Transgender and nonbinary middle-distance runner Nikki Hiltz ran the second fastest time ever of any American in the women's 1500-meter race at the U.S. Olympic Trials Sunday, qualifying for the ...

  30. Nikki Hiltz, transgender, nonbinary runner, qualifies for Olympics

    Hiltz, 29, whose sex was assigned as female at birth, earned a ticket to the Paris Games with a meet-record time of 3:55.33 in the women's 1500-meter final of the U.S. Olympic trials on June 30.