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Testosterone Hormone Replacement Therapy

The benefits and results of testosterone hormone replacement therapy (hrt) for transsexuals who are undergoing the gender reassignment transition process..

Depo-testosterone Vials

Depo-testosterone vials are available by prescription in a 10mL and a 1mL size.

  • Letter from therapist to begin hormones
  • Blood work and testosterone levels

Blood work will be taken more frequently just after beginning hormone therapy. It is important to monitor your testosterone and CBC results after introducing the new hormone into the body. Testosterone intake may need to be increased if it is too low, or decreased if it is too high. Testosterone can increase red blood cell count, thereby increasing the probability of side effects . Testosterone can be given as:

  • An intramuscular injection, usually the glutes or thigh;
  • A transdermal implant placed under the skin, usually the abdomen or buttocks; or
  • An oral tablet, not recommended because of liver toxicity

In biological men, testosterone is a hormone produced by the endocrine system though the testes. It is responsible for:

  • Libido (sex drive)
  • Development of male secondary sex characteristics, such as body hair growth, penile growth, and deepening of the voice

Physical Effects of Testosterone Hormone Replacement

Testosterone hormone replacement initiates the development of secondary sex characteristics.

Irreversible changes

  • Deepening of the voice
  • Facial and body hair development
  • Enlargement of the clitoris
  • Male pattern baldness

Reversible changes

  • Muscle development
  • Increased libido
  • Redistribution of body fat
  • Cessation of ovulation and menstruation
  • Increased sweat
  • Changes in body odor
  • Prominence of veins
  • Coarse skin
  • Elevated blood lipids (cholesterol and triglycerides)
  • Increased red blood cell count

Psychological Effects of Testosterone Hormone Replacement

* The information contained is not a replacement for medical advice and should not be used for medical treatment or hormone replacement therapy without the supervision of a licensed physician. femaletomale.org seeks to provide relevant information about gender reassignment, but under no circumstances should the information provided challenge or take the place of the authority of a medical professional. Disclaimer

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Practical Guidelines for Transgender Hormone Treatment

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

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

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

    1. Oral

  • Testosterone undecanoate*      160–240mg/day

   2. Parenterally (i.m. or subcutaneous)

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

   3. Transdermal

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

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

Monitoring for transgender men (FTM) on hormone therapy:

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

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

     1. Anti-androgen

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

    2. Oral estrogen

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

    3. Parenteral estrogen

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

    4. Transdermal estrogen

  • Estradiol patch     0.1–0.4mg/2X week

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

Monitoring for transgender women (MTF) on hormone therapy:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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.

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.

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

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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

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By Elizabeth Boskey, PhD Elizabeth Boskey, PhD, MPH, CHES, is a social worker, adjunct lecturer, and expert writer in the field of sexually transmitted diseases.

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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

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

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Department of Obstetrics and Gynaecology, ASTT Lecco, Ospedale Leopoldo Mandic, Merate, 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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  • Feminizing hormone therapy

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

Feminizing hormone therapy involves taking medicine to block the action of the hormone testosterone. It also includes taking the hormone estrogen. Estrogen lowers the amount of testosterone the body makes. It also triggers the development of feminine secondary sex characteristics. Feminizing hormone therapy can be done alone or along with feminizing surgery.

Not everybody chooses to have feminizing 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

Feminizing 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 feminizing 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.

Feminizing 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 feminizing hormone therapy if you:

  • Have a hormone-sensitive cancer, such as prostate 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.

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Research has found that feminizing 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 feminizing hormone therapy.

Complications can include:

  • Blood clots in a deep vein or in the lungs
  • Heart problems
  • High levels of triglycerides, a type of fat, in the blood
  • High levels of potassium in the blood
  • High levels of the hormone prolactin in the blood
  • Nipple discharge
  • Weight gain
  • Infertility
  • High blood pressure
  • Type 2 diabetes

Evidence suggests that people who take feminizing hormone therapy may have an increased risk of breast cancer when compared to cisgender men — men whose gender identity aligns with societal norms related to their sex assigned at birth. But the risk is not greater than that of cisgender women.

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

Feminizing 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 testicles might not recover enough to ensure conception without infertility treatment.

If you want to have biological children, talk to your health care provider about freezing your sperm before you start feminizing hormone therapy. That procedure is called sperm cryopreservation.

How you prepare

Before you start feminizing 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 sperm freezing and fertility.

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 silicone injections, 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 feminizing 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.

Feminizing hormone therapy typically begins by taking the medicine spironolactone (Aldactone). It blocks male sex hormone receptors — also called androgen receptors. This lowers the amount of testosterone the body makes.

About 4 to 8 weeks after you start taking spironolactone, you begin taking estrogen. This also lowers the amount of testosterone the body makes. And it triggers physical changes in the body that are caused by female hormones during puberty.

Estrogen can be taken several ways. They include a pill and a shot. There also are several forms of estrogen that are applied to the skin, including a cream, gel, spray and patch.

It is best not to take estrogen as a pill if you have a personal or family history of blood clots in a deep vein or in the lungs, a condition called venous thrombosis.

Another choice for feminizing hormone therapy is to take gonadotropin-releasing hormone (Gn-RH) analogs. They lower the amount of testosterone your body makes and might allow you to take lower doses of estrogen without the use of spironolactone. The disadvantage is that Gn-RH analogs usually are more expensive.

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

  • Fewer erections and a decrease in ejaculation. This will begin 1 to 3 months after treatment starts. The full effect will happen within 3 to 6 months.
  • Less interest in sex. This also is called decreased libido. It will begin 1 to 3 months after you start treatment. You'll see the full effect within 1 to 2 years.
  • Slower scalp hair loss. This will begin 1 to 3 months after treatment begins. The full effect will happen within 1 to 2 years.
  • Breast development. This begins 3 to 6 months after treatment starts. The full effect happens within 2 to 3 years.
  • Softer, less oily skin. This will begin 3 to 6 months after treatment starts. That's also when the full effect will happen.
  • Smaller testicles. This also is called testicular atrophy. It begins 3 to 6 months after the start of treatment. You'll see the full effect within 2 to 3 years.
  • Less muscle mass. This will begin 3 to 6 months after treatment starts. You'll see the full effect within 1 to 2 years.
  • More body fat. This will begin 3 to 6 months after treatment starts. The full effect will happen within 2 to 5 years.
  • Less facial and body hair growth. This will begin 6 to 12 months after treatment starts. The full effect happens within three years.

Some of the physical changes caused by feminizing hormone therapy can be reversed if you stop taking it. Others, such as breast development, cannot be reversed.

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

  • Keep track of your physical changes.
  • Monitor your hormone levels. Over time, your hormone dose may need to change to ensure you are taking the lowest dose necessary to get the physical effects that you want.
  • Have blood 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.
  • Prostate cancer screening. This should be done according to prostate cancer screening recommendations for cisgender men your age.
  • Monitoring bone health. You should have bone density assessment according to the recommendations for cisgender women your age. You may need to take calcium and vitamin D supplements for bone health.

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  • Tangpricha V, et al. Transgender women: Evaluation and management. https://www.uptodate.com/contents/search. Accessed Oct. 10, 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 Oct. 10, 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. Gender-affirming hormone therapy (adult). Mayo Clinic; 2022.
  • Nippoldt TB (expert opinion). Mayo Clinic. Sept. 29, 2022.
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Treatment - Gender dysphoria

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

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

Treatment for children and young people

If your child is under 18 and may have gender dysphoria, they'll usually be referred to the Gender Identity Development Service (GIDS) at the Tavistock and Portman NHS Foundation Trust.

GIDS has 2 main clinics in London and Leeds.

Your child or teenager will be seen by a multidisciplinary team at GIDS 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
  • a referral to a specialist hormone (endocrine) clinic for hormone blockers for children who meet strict criteria (at puberty)

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) to see if they can take hormone blockers as they reach puberty. This is in addition to psychological support.

Puberty blockers and cross-sex hormones

Puberty blockers (gonadotrophin-releasing hormone analogues) pause the physical changes of puberty, such as breast development or facial hair.

Little is known about the long-term side effects of hormone or puberty blockers in children with gender dysphoria.

Although GIDS advises this is a physically reversible treatment if stopped, it is not known what the psychological effects may be.

It's also not known whether hormone blockers affect the development of the teenage brain or children's bones. Side effects may also include hot flushes, fatigue and mood alterations.

From the age of 16, teenagers who've been on hormone blockers for at least 12 months may be given cross-sex hormones, also known as gender-affirming hormones.

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 cross-sex hormone treatment may cause temporary or even permanent infertility.

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

There is some uncertainty about the risks of long-term cross-sex hormone treatment.

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 GIDS.

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
  • Services for children and young people (PDF, 1.15Mb)
  • Amendments to services for children and young people (PDF, 16kb)

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

  • Case Report
  • Open access
  • Published: 19 October 2020

In a case of female-to-male sex reassignment, testosterone therapy switches on an underlying Brugada

  • Patrizia Vivona 1 , 2 ,
  • Federica Dagradi 3 &
  • Michele M. Ciulla   ORCID: orcid.org/0000-0002-6717-6065 1 , 2  

International Journal of Arrhythmia volume  21 , Article number:  17 ( 2020 ) Cite this article

1923 Accesses

1 Citations

Metrics details

The Brugada syndrome, diagnosed by a typical electrocardiographic pattern, is a genetic condition characterised by an increased risk of potentially lethal ventricular arrhythmias and sudden cardiac death. Even if its pathophysiological mechanism is unknown, its prevalence in male suggested a possible hormonal involvement.

Case presentation

In this case involving a woman who underwent a female-to-male sex reassignment, we documented that testosterone administration was able to switch on and, when stopped, to switch off a latent pattern of Brugada.

Conclusions

Our observation strongly supports a possible involvement of testosterone in the ECG manifestation of Brugada syndrome even if the general low prevalence of the Brugada syndrome does not support to screen every female-to-male sex reassignment.

Introduction

Sex change is a dramatic and controversial procedure that allows anatomical, legal, and psychosocial adaptations to another gender. Hormonal treatments are administered as a part of the procedures for sex reassignment and, in a female-to-male reassignment, include a testosterone preparation and a possible testosterone maintenance [ 1 ]. In theory, the hormonal changes over time could alter the cardiovascular risk profile related to the different gender, even if it appears to be rather safe in the short and medium term, as a study seems to suggest [ 2 ]. Unfortunately, there are no data in the literature on the possibility that a latent pathological phenotype can be, eventually, switched on by testosterone therapy. In this regard, we know that the Brugada syndrome, recognised since 1992, occurs in males about 8–10 times more than in women [ 3 ]; thus, a possible hormonal involvement might play a role. Currently, the diagnosis is based on the detection of a typical electrocardiographic pattern (type 1). Furthermore, there are twelve known genes potentially responsible for the condition [ 4 ], and all genotypes correlate with alterations of cardiac action potential determined by a decrease in inward sodium or calcium currents, or an increase in outward potassium currents. Although there are some publications [ 4 , 5 ] connecting the hormonal influence with the evidence of arrhythmias and Brugada syndrome, here we present a case report that, for the first time, supports a direct connection between androgen therapy and the Brugada pattern switch-on. This case is about a young woman who underwent a sex change and, after she started a testosterone-based therapy, she manifested a typical Brugada pattern on ECG.

In a 30-year-old woman admitted to gynaecology for a sex change, an ECG was obtained and a Brugada syndrome was suspected. Previous ECGs were normal. She took testosterone for about a year. In a subsequent ECG performed during a routine cardiological visit, it was evident a 1-mm ST segment elevation in V2 lead. She was, therefore, referred to our Center of Genetic Heart Disease and Arrhythmias. She had not have family history of sudden death and she denied syncope in her personal history, but palpitations were reported when assuming testosterone. A dosage of plasma testosterone and a 24-hour Holter ECG were obtained. Thereafter, a flecainide test was performed unmasking a typical ECG pattern of Brugada (Fig.  1 ). Genetic tests were negative for mutations related to SCN5A [ 6 ], the gene coding for the α-subunit of the most abundant sodium channel in the heart; after momentary suspension of testosterone, the ECG no longer showed a Brugada pattern. When the hormone was reintroduced, the Brugada pattern reappeared on the ECG alone with the same episodes of palpitation, while major arrhythmias were never documented. Original ambulatory ECG tracings done during the follow-up are shown in Fig.  2 .

figure 1

Original tracing showing basal (from left, first panel), pre-test (from left, second panel), test (from left, third panel), and post-test (from left, last panel) ECG. In the basal ECG, incomplete right bundle branch block and saddle-back-like ST deviation in V1. The test ECG after flecainide clearly shows a typical pattern of Brugada. Basal tracing was obtained before starting testosterone therapy; the suspect ECG was the pre-test showing the changes in ST segment

figure 2

Original tracings showing an ambulatory ECG done during a therapy suspension period (top panel) and an ECG done during the testosterone therapy (bottom panel)

The pathophysiological mechanism for Brugada syndrome is essentially unknown. The debate whether Brugada syndrome is linked to heart depolarisation or repolarisation is still open. The identification of mutations in the genes encoding the sodium channels, suggests a disturbance of the depolarisation; for a long time, it was thought that at the base of the pathophysiological mechanism was the impaired depolarisation localised in the right ventricular outflow tract level, due to a mismatch between the transient outward potassium current Ito and the sodium current depolarising (INa). The right ventricular outflow tract is the area considered as the arrhythmogenic substrate of the disease because it presents different characteristics of the distribution of ion channels, compared to the other parts of the heart, already present in the embryonic life that persist into the adult life. One experimental study in dogs demonstrates that transmural difference in INa in female was reduced to values observed in male by testosterone [ 7 ]. If these results could suggest to hypothesise that INa dispersion is modulated by testosterone, this could be an important factor supporting gender differences in myocytes action potential duration dispersion and arrhythmias; similarly, we might assume that the same could happen on cardiomyocytes of a woman who is taking androgens.

A woman that undergoes a sex change is usually pre-treated with testosterone aiming at the virilisation of traits, including a deepening of the voice, the production of male-pattern body hair, growth and physical contours, and cessation of menses. In our case, as we have clearly demonstrated by an appropriate test, the androgen administration/cessation was able to switch on and off a latent pattern of Brugada. Due to the general low prevalence of the Brugada syndrome our observation does not support to screen every female-to-male sex reassignment. On the contrary, it strongly supports a possible involvement of testosterone in ion channelopathies like the Brugada syndrome [ 8 , 9 , 10 ]. However, it will be prudent to offer a baseline ECG in preparation for the administration of testosterone in order to prevent the rise of a fatal syndrome.

Availability of supporting data

Since it is a single case report, only clinical records were available.

Abbreviations

electrocardiogram

sodium channel, voltage-gated, type V, alpha subunit

late sodium current depolarising

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Patrizia Vivona & Michele M. Ciulla

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Vivona, P., Dagradi, F. & Ciulla, M.M. In a case of female-to-male sex reassignment, testosterone therapy switches on an underlying Brugada. Int J Arrhythm 21 , 17 (2020). https://doi.org/10.1186/s42444-020-00025-5

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USA Boxing slammed for new transgender policy that allows biological men to compete against women

A new kind of fight is brewing in the boxing world.

USA Boxing, the governing body of the sport in the United States, is being slammed for its “pathetic and disgusting” new transgender policy that allows biological men to compete against biological women.

Under the new policy, included in the 2024 rule book, male boxers who transition can compete in the female category so long as they meet certain criteria.

Those under the age of 18 are still required to compete as their birth gender, but adults can choose their category as long as they state their new gender identity and fully complete gender reassignment surgery.

Transgender athletes must also participate in regular hormone testing.

Boxers who transitioned into women are required under the new policy to have testosterone levels under five nanomoles per liter for three years prior to their first competition in the “female” category, and their total testosterone levels must be below five nmol/L throughout their period of eligibility.

Those competing as men, meanwhile, must show levels about 10 nmol/L for the same period.

“The purpose of this policy is to provide fairness and safety for all boxers,” USA Boxing says in its new policy.

But critics say it is dangerous for the biological females that the transgender women will be competing against.

“USA Boxing wants to get women killed,” Jenna Ellis, a constitutional lawyer and former senior legal advisor to Trump, posted on X.

Riley Gaines, a former NCAA swimmer who has made a name for herself speaking out against transgender female athletes competing against male athletes, echoed this sentiment, writing : “Mark my words, it will take a woman getting killed before these misogynistic fools wake up.”

Collin Rugg, a conservative political commentator, also joked that “South Park was right again,” as he shared a GIF of an episode in which Randy Savage claims to be a transgender boxer and starts fighting women.

“Clown world,” he wrote.

Conservative firebrand Rep. Lauren Boebert even went as far as to claim that the new policy lets men “beat women up in a boxing ring.

“Let’s call this what it is. They’re going to allow men to beat women up in a boxing ring,” she wrote . “This is pathetic and disgusting.”

Female boxers have also spoken out against the new policy, with MMA fighter Claressa Shields saying : “This is idk… Not the right decision.”

Others noted that hormone therapy is otherwise banned in the sport.

“By default, this should make trans athletes ineligible for competition. Period,” professional boxer Mikaela Mayer wrote on X.

“Doesn’t matter how you feel about the situation, fact is, it’s illegal and completely disrupts the even playing field that sport works so hard to create.”

Ebanie Bridges, the bantamweight world titleholder, also said the policy has no place in the world of boxing.

“I don’t care about ‘political correctness,’” she wrote. “It’s politically incorrect to have a man fighting a woman… and [I don’t care] that’s exactly what this is… this society is too soft… This is our health and safety.

“The girls need to stick together or women’s sports in 50 years will be filled with male-born champions.”

She added in a follow-up post : “It’s bad enough having trans women breaking records in other sports like track and field, swimming and powerlifting but it’s a bit different to them breaking our skulls in combat sports where the aim is to HURT YOU, not just break a record.

“It ain’t just about the test levels, what about their bone density and a heap of other biological factors. 

“Cutting ur bits off and adding boobs won’t take back the masculine maturity your body has gone thru before you decided u are now a woman. #ISaidWhatISaid.”

USA Boxing slammed for new transgender policy that allows biological men to compete against women

Trans adults on edge as legislatures broaden focus beyond children

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Medical school is hard enough, but Charlie Adams’s existence was on the line, so he took a day off from clinic rotations in Kansas City and drove three hours to the Missouri Capitol.

Republican legislators had proposed nine bills to restrict transgender rights. Two sought to limit the definition of sex. Another gave doctors the right to discriminate against trans people. And four aimed to keep them out of the bathrooms that match their identities.

Adams, 27, has a full beard and a deep voice, and as he spoke recently to a committee of legislators, a patch of chest hair peeked out from his navy blue scrubs.

“Do you want to see me in the women’s restroom next time you’re at the hospital?” he asked.

Adams spoke for two minutes, thanked the legislators, then scurried out. He had eight more bills to fight.

The legislation in Missouri is part of a record number of proposals that could significantly reshape the way transgender people live their lives. Republican-dominated legislatures have already enacted more than 100 laws to limit LGBTQ+ rights over the past few years, but most affected adolescents and schools. Now, policymakers are increasingly turning their focus to adults.

Lawmakers in Iowa , West Virginia and other states have introduced bans on transgender people using bathrooms that align with their gender identity. Officials elsewhere are attempting to narrowly define sex in a way that will leave trans people misgendered on official documents. The head of Florida’s Department of Motor Vehicles announced in late January that the agency will no longer allow trans adults to change the gender markers on their licenses and threatened criminal charges for those who don’t comply.

So far, no legislature has outright prohibited adults from transitioning, but last year, Florida passed the nation’s first health-care restrictions for trans adults, and some within the Republican Party believe other states will soon follow its lead. A handful of legislators have said they don’t believe in the care or hope to eradicate it completely.

The lawmakers pushing the bills universally contend there should be limits on how far society goes to embrace transgender adults. Some do not believe in the concept of having a gender identity different from one’s biological sex.

“There is no such thing as gender-affirming care,” Ohio state Sen. Kristina Roegner (R) said in a January speech on the Senate floor. “You can’t affirm something that doesn’t exist.”

Adams said he is “overwhelmed, scared and angry.”

“Even if most of the proposed bills don’t pass, the constant vilifying of us is already doing damage,” Adams said. “I used to think if I could get into the rooms and organizations I’m in now, if I could only share the stories of all the amazing trans people I know, and if they got to know me as a colleague, they would understand we’re just people and our rights are worth protecting. But I’m learning lately that that may not be enough.”

Once disputed, now embraced

State legislators largely left trans people undiscussed until 2016, when, less than a year after the Supreme Court legalized same-sex marriage nationwide, North Carolina passed the nation’s first bathroom-restrictions bill.

The legislation was hugely unpopular. The NBA pulled its All-Star Game from the state, the NCAA withdrew a number of sporting events, and several musicians, including Bruce Springsteen and Pearl Jam, canceled concerts there. All told, the legislation cost the state $3.7 billion , and the governor who had signed the bill lost his reelection campaign.

Still, conservative strategists believed trans bills could become a political winner. In meetings and emails , they described a game plan that started by restricting participation in sports, then ramped up to banning gender transition care for adolescents.

Though polls have found that Americans are split on how they view gender transition care for minors, the bills have passed with increasing ease. States began trying to ban the treatments in 2020, but the bills all died without becoming law. Arkansas passed the first youth health-care ban in 2021. Alabama approved the second in 2022, and last year another 21 states followed suit. District courts have enjoined many of those, but appeals courts in Cincinnati and Atlanta have allowed them to take effect .

As state after state prohibited gender transition care for young people, conservative policymakers said they were concerned that adolescents’ brains weren’t developed enough to decide to take puberty blockers or cross-sex hormones. Adults, the lawmakers said, could do whatever they wanted.

Then, in April 2023, Missouri Attorney General Andrew Bailey (R) went a step further and announced new regulations that advocates said essentially banned the care in the state for everyone, even adults.

The ruling terrified Adams. He asked his pharmacist to give him as much testosterone as he legally could, but that only covered three months. Other trans people went online to find hormones illegally, and Adams researched those options, too. Going off testosterone was “not an option,” he said, and he planned to do whatever he could to stay on it.

“I’m not going back,” he said. “My life before testosterone, I was not happy. And now I finally get to live a good life. I have come so far and found so much happiness. The thought of detransitioning because of lack of access is the worst thing that could possibly happen to me.”

Bailey eventually backed off after the courts got involved. But a few weeks later, in May, Florida legislators passed their own adult restrictions.

In session , the bill’s Republican sponsor described it as a measure to protect children. But seven pages into the bill , he also outlined new regulations that cut thousands of trans adults off their hormones. From now on, the law stipulated, trans adults could only receive hormones from a medical doctor who sees them in person.

Because more than half of trans people are low-income and nurse practitioners are cheaper than doctors, clinicians and activists say roughly 80 percent of trans adults in Florida were getting hormones from nurses, a standard medical practice the law banned. Others saw doctors through telehealth services.

Spike Poma, an intersex trans man from Polk County in Central Florida, had been getting testosterone from a Planned Parenthood nurse practitioner for four years, but after the bill passed, he said, the clinic canceled his prescription.

Seven months later, Poma still has not been able to access testosterone, and he is struggling with numerous health problems because of it.

“Life isn’t living,” he said. “It’s just surviving at this point.”

‘Every aspect of our lives’

Nearly every red state passed a sports or health-care ban for minors last year, and now lawmakers are using similar language to reach into other avenues of life.

Last year, four predominantly Republican state legislatures — Kansas, Montana, North Dakota and Tennessee — passed laws narrowly defining sex in a way that not only makes it harder for trans adults to update their legal documents but also erodes their protections against discrimination in housing and governmental programs. The GOP governors of Nebraska and Oklahoma made similar changes by issuing executive orders, and 13 others are considering comparable bills.

In late January, Republican Iowa Gov. Kim Reynolds introduced a bill that would prohibit trans people from updating their driver’s license unless they have surgery. (Last year, a Post-KFF poll found that only 1 in 6 trans adults has had gender-affirming surgery.) Those who do would have to list both their sex assigned at birth and their gender identity.

“Just like we did with girls’ sports, this bill protects women’s spaces and rights afforded to us by Iowa law and the constitution,” Reynolds said in a statement.

Other states are considering proposals to create what trans people describe as “registries.” In Florida , every resident would have to sign an affidavit certifying that the sex listed on their driver’s license is the sex they were assigned at birth. And in Ohio, the governor issued a draft order this month that would require health-care professionals to report every time they diagnose someone as trans, prescribe cross-sex hormones or perform a gender reassignment surgery. According to the governor’s rules, those reports will be sent to the General Assembly.

Cam Ogden, a trans woman who co-runs the advocacy group Trans Allies of Ohio, said she worries the data will be used in bad faith. Republicans have a supermajority in the Ohio House and Senate, and they have proposed six bills to limit trans rights this session.

“The General Assembly hasn’t exactly been passing legislation to protect trans people the last few years,” Ogden said. “If the data is intended to help the legislature, the only way it can is to help them attack us further.”

Logan Casey, a trans Missourian who works as the senior researcher at the independent think tank Movement Advancement Project, said the number and diversity of bills can be mind-boggling to track.

“We’re under attack across virtually every aspect of our lives, and each new day is bringing with it some new escalation,” Casey said.

Indeed, as major corporations have backed away from boycotts, Republicans are returning to bathroom bills similar to the one North Carolina abandoned in 2016. Utah passed one in late January, and Missouri legislators are still looking for a way to pass one of theirs.

Missouri state Rep. Mark Matthiesen, a Republican who sponsored one of four bathroom bills, said he decided to act after a group of women in conservative St. Charles County told him they don’t feel safe sharing the locker room at a local pool with trans women.

As more trans people undergo medical interventions , Matthiesen said, and as workplaces have offered them greater protections, “conservatives are finally standing up and saying, no, we can’t be part of this. Enough is enough. This has gotten out of hand, and we’ve got to stop promoting it.”

Matthiesen said he has received hate mail from “liberal women all over St. Louis,” but he doesn’t fear the kind of boycotts North Carolina faced six years ago. In fact, he said, conservatives are more likely to boycott a company such as Bud Light if they “virtue-signal too far,” as they did last year, he said, when the beer company partnered with a trans woman in a social media promotion.

Still, Matthiesen said his bill is unlikely to pass in its current form. According to the LGBTQ+ advocacy group Human Rights Campaign , nearly 90 percent of proposed anti-LGBTQ+ bills died last year without becoming law.

“Even the conservatives want to give the liberals their ability to run their own lives,” Matthiesen said. “One of the main oppositions to my bill has to do with private property rights. I’m trying to regulate what a private business can do and allow.”

Matthiesen said he is studying Utah’s bill to craft a new version that limits the regulation to government buildings and other public spaces.

Adams said he is unsure what he’ll do if the law goes through. He suspects he could keep using the men’s room without drawing suspicion.

“But I’ll be breaking the law if I do that,” he said. “If I do go into the women’s restroom, I’m going to freak people out. But I’ll be following the law. Then there’s a good chance I could get beaten up. They may think I’m a man trying to sneak in the women’s restroom. But how do I prove to them that I’m a trans man? I’m not going to drop my pants or have my birth certificate with me there.”

‘Small bites’

Late last month, Republican state legislators from Ohio and Michigan talked about the future of gender transition care in an audio discussion via the social media site X . (Erin Reed, an independent researcher who tracks anti-LGBTQ+ legislation first reported the conversation.)

The event was billed as a discussion about minors, but the legislators invited Prisha Mosley, a woman who transitioned to male as an adult, then later detransitioned. Mosley sued her doctors in North Carolina last year and has accused them of lying and telling her testosterone would cure “her numerous, profound mental and psychological health problems,” including borderline personality disorder and trauma from sexual assault.

As the legislators talked, Michigan state Rep. Josh Schriver (R) suggested they should not stop at banning the care for young people.

“In terms of endgame, why are we allowing these practices for anyone?” Schriver said. “If we are going to stop this for anyone under 18, why not apply it for anyone over 18?”

Ohio state Rep. Gary Click (R), who led his state’s successful campaign to ban care for minors, cautioned that lawmakers might have to “take small bites” to “get any legislation across the finish line,” but told Schriver his comments were a “very smart thought.”

Click told The Washington Post he was trying to be polite, not suggesting that he intends to pass additional legislation. Though Click has criticized Planned Parenthood and other clinics that offer hormones without requiring mental health assessments, he said he believes adults should be able to do whatever they want.

Another Michigan Republican state legislator, Rep. Brad Paquette, later told the nonprofit news site Michigan Advance he agreed that gender transition harms adults and had subsequently sent a letter to every hospital that treats trans patients to learn more.

Still, one prominent conservative strategist says he doesn’t expect states will pursue full health-care bans for adults anytime soon. Terry Schilling, executive director of the American Principles Project, a conservative nonprofit that raises money for anti-trans legislation, said adult bans seem so far-fetched, his group hasn’t even poll-tested them.

But, Schilling said, many state legislators came away from public hearings about minors concerned about the overall landscape of gender care. A small number of detransitioners traveled state to state to say they regretted taking hormones and having surgeries to reshape their bodies.

“They’re acknowledging that there was harm done to these kids, and now they’re thinking, well, the harm is actually also being done to these adults, too,” Schilling said.

Schilling said he expects “many more states” to follow Florida’s lead in passing restrictions. Ohio Gov. Mike DeWine (R) proposed a similar set of regulations in January, but he abandoned them last week. His spokesman told The Post that the governor is focused on “protecting children” and issuing rules “where there was consensus.” After reviewing nearly 4,000 public comments, the spokesman said, the governor decided to redraft his proposal.

Still, trans Ohioans say they fear lawmakers will try again. Republican legislators tried three times to pass a health-care ban for adolescents before ultimately succeeding in late December.

“This is far from the end,” Ogden, of Trans Allies of Ohio, said.

None of the nine Missouri bills have become law yet, but late last month, while Adams was working a rotation, a committee passed a measure that would allow doctors to refuse to treat trans patients. Of all the bills that target adults, Adams said that one might hurt the most.

“We take an oath,” Adams said. “I would without hesitation treat any person regardless of their beliefs, and I did when I worked in the ER. It hurts that even though all my intentions are good, even for someone who hates me, and I’d never want them denied care, they are trying to make it legal for people to deny me care.”

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Transwoman Elite Athletes: Their Extra Percentage Relative to Female Physiology

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There is increasing debate as to whether transwoman athletes should be included in the elite female competition. Most elite sports are divided into male and female divisions because of the greater athletic performance displayed by males. Without the sex division, females would have little chance of winning because males are faster, stronger, and have greater endurance capacity. Male physiology underpins their better athletic performance including increased muscle mass and strength, stronger bones, different skeletal structure, better adapted cardiorespiratory systems, and early developmental effects on brain networks that wires males to be inherently more competitive and aggressive. Testosterone secreted before birth, postnatally, and then after puberty is the major factor that drives these physiological sex differences, and as adults, testosterone levels are ten to fifteen times higher in males than females. The non-overlapping ranges of testosterone between the sexes has led sports regulators, such as the International Olympic Committee, to use 10 nmol/L testosterone as a sole physiological parameter to divide the male and female sporting divisions. Using testosterone levels as a basis for separating female and male elite athletes is arguably flawed. Male physiology cannot be reformatted by estrogen therapy in transwoman athletes because testosterone has driven permanent effects through early life exposure. This descriptive critical review discusses the inherent male physiological advantages that lead to superior athletic performance and then addresses how estrogen therapy fails to create a female-like physiology in the male. Ultimately, the former male physiology of transwoman athletes provides them with a physiological advantage over the cis-female athlete.

1. Introduction

Sports have been a major part of human culture throughout history, with ancient Greeks and Romans showing mastery through competition. Indeed, few areas of culture have the power to influence people as strongly as sports. It is often the intense emotional bond fans develop with teams and players that underlies their passion for sport. Fans can live vicariously through their chosen elite athletes and sportsmen and women are often considered role models for society. Amateur athletes and young emerging hopefuls strive to reach the highest levels within their chosen sport by modeling their idols.

Given the passion associated with sports, any controversy surrounding a result can lead to strong debate, especially if there is a perception that fairness has been jeopardized. The concept of fairness is the justification for dividing most sports into male and female categories. Without such segregation, females would have little chance of winning. World records show that males consistently perform better in sports [ 1 , 2 , 3 , 4 , 5 ]; the most recent Olympic gold, silver, and bronze medal results show that females would not have medaled in an open competition for a wide variety of sports (same distance raced by male and female) ( Table 1 ; https://www.olympic.org/olympic-results (accessed on 1 January 2019). This remains despite increased female participation in sports [ 6 ] and female-centric technologies applied to training and equipment. Despite the recognition of the male dominance of athletic performance, the male and female divisions are becoming blurred as transgender women (individuals that are born as male and identify as female) athletes enter the female division. The inclusion of transgender women athletes has raised concerns about the fairness of the female division for biological female athletes (ciswomen, where gender identity aligns with their biological sex).

Gold medal distances or times for selected sporting events recorded for males and females at the RIO Olympics 2016.

Distances are given as meters (m), and times are given as seconds (s), minutes (mins), or hours (h).

To compete in the female division as defined by current International Olympic Committee (IOC) regulations, a transgender woman athlete must agree to gender-affirming hormone therapy to lower, and then maintain, testosterone levels to below 10 nmol/L for one year (IOC Consensus Meeting on Sex Reassignment and Hyperandrogenism November 2015). Estradiol therapy is the common hormonal regime used to reduce testosterone levels in transwomen athletes [ 7 , 8 ].

The underlying question asked in this descriptive review is whether the IOC 2015 guidelines that allow transgender women to compete in the female division are fair. In order to address this question, the review aims to (A) explain the physiology behind why males perform better in sport and (B) document why male physiology cannot simply be reformatted into female physiology by estrogen therapy in transwomen athletes. In preparing this review, studies targeting (1) sex differences in athletic performance (2) testosterone administration to males or females and how this affects athletic performance and (3) transfemale or transmale physiology post-transitioning were included. The objective of this review is to increase awareness of male physiology and how it pertains to athletic performance so as to highlight issues facing the female sports division. Most importantly, the review aims to identify key physiological factors that need to be considered by sporting organizations and relevant authorities when interpreting fairness in sport.

2. Male Physiology Provides an Athletic Performance Advantage

Testosterone drives anatomical and physiological sex differences in the human body ( Figure 1 ). These sex differences can be architectural and therefore permanent, or can be influenced by adult-level, circulating testosterone concentrations, and therefore modifiable. Permanent sex differences that affect athletic performance involve the (i) brain, (ii) skeletal structure, and (iii) cardiorespiratory system. Modifiable sex differences include testosterone effects on (i) muscle mass and strength and (ii) aerobic capacity.

An external file that holds a picture, illustration, etc.
Object name is ijerph-19-09103-g001.jpg

Irreversible changes to male physiology. Figure 1 shows the irreversible changes of testosterone conditioning throughout life. Testosterone masculinizes the brain in utero and during early life. Testosterone drives anatomical structure design specific to the male skeleton. Testosterone drives muscle mass, muscle fiber type, and muscle memory. Most of the effects driven by testosterone cannot be reversed with estradiol (or cross) hormone therapy.

2.1. Prenatal Testosterone and the Male-like Brain

Anatomical sex differences in the brain appear during early life when the in utero and postnatal surges of testosterone masculinize the male brain [ 9 , 10 ]. Ascribing specific behaviors to these anatomical sex differences has been challenging [ 11 ] and may involve differences in cell morphology as well as the connections between brain networks [ 12 , 13 , 14 , 15 , 16 ]. For example, diffusion magnetic resonance imaging (MRI) shows increased intraconnectivity in males for regions of the brain attributed to perception-action coordination, auditory/visual spatial awareness and processing, cognitive processes and complex reasoning and control [ 16 ]. Females, on the other hand, show more interconnectivity in those regions of the brain attributed to memory, social cognition, and non-verbal reasoning. The sex-specific connectivity of these subnetworks may underlie the ability of males to show consistently higher levels of motor and visual spatial skills in addition to elevated sensory input from vision and proprioception [ 17 , 18 , 19 , 20 ].

There is little debate that better motor skills, visual spatial skills, and proprioception will improve coordination and subsequent athletic performance. These differences in brain structure are evident in childhood, with 8–13 year olds showing behavior patterns that become further differentiated with the onset of puberty and aging into adulthood [ 16 ].

An aggressive, competitive nature also underpins better athletic performance [ 21 ]. Although it is difficult to attribute prenatal testosterone exposure directly to levels of aggression in the adult, indirect evidence suggests that such a relationship may exist. Development of the fourth digit (4D), but not the second digit (2D), is highly sensitive to testosterone, so that in utero androgen exposure results in lower 2D:4D ratios in males compared to females and is considered an index of prenatal testosterone exposure [ 22 , 23 , 24 , 25 ]. There is a clear association between 2D:4D ratios and male-typical behaviors [ 24 , 26 ] and, interestingly, professional male football players with low 2D:4D ratios receive more yellow or red card penalties [ 27 ]. Even with females, lower 2D:4D ratios in females are associated with the more aggressive form of sabre fencing [ 28 ]. Such examples suggest the possibility that in utero androgen exposure leads to later-life aggressiveness.

2.2. Testosterone and Muscle Mass

For many decades, it has been recognized that testosterone drives muscle mass and clear sex differences exist. For example, elite male athletes have, on average, more muscle mass than elite female athletes, for any given body weight [ 29 ]. Males have approximately twice the cross sectional area of upper body muscle, and 30% more cross sectional area of lower body muscle relative to females [ 30 ]. The difference in muscle mass emerges during puberty as circulating testosterone levels increase in boys [ 31 ].

Circulating testosterone is the key physiological parameter driving muscle mass in both males and females [ 32 , 33 , 34 ]. For example, 19–40 year old males given supraphysiologic doses of testosterone for 10 weeks increased muscle mass, muscle size, and strength by up to 10%. If this treatment was combined with strength training, the increase in muscle mass was 27% [ 32 ]. A follow-up study by the same laboratory [ 33 ] showed that the testosterone effect on muscle mass was dose-dependent. Males, 18–35 years old, were treated with a gonadotropin-releasing hormone (GnRH) agonist to suppress endogenous testosterone production and then administered testosterone for 20 weeks at either 25, 50, 125, 300, or 600 mg, resulting in circulating concentrations of 8.8, 10.6, 18.8, 46.7, and 82.2 nmol/L, respectively, covering low physiological to supra-physiological levels. Supraphysiological concentrations (>40 nmol/L) increased leg muscle mass and strength, whereas mid-range testosterone level administration increased muscle mass with maintenance of leg strength. Interestingly, low testosterone levels (<10 nmol/L) maintained leg muscle mass and strength. This latter finding is in keeping with research in rodents that shows testosterone is not needed for muscle maintenance in adult male mice [ 35 ]. In this study, orchidectomised mice aged from young through to old were assessed for muscle mass after 28 days of testosterone depletion. Only the youngest mice showed reduced muscle mass, while the older, adult mice showed no effect on muscle mass. Therefore, it appears that testosterone may not be critical for maintenance of muscle mass in mature male mice [ 35 ]. In females, testosterone administration to raise circulating levels from 0.9 nmol/L to 4.3 nmol/L in young women (average 28 years) increased muscle mass and strength, as well as enhanced athletic performance as evidenced by time to exhaustion and Wingate testing [ 36 ].

2.3. Testosterone and Bone Structure

Bone structure and bone length changes in both sexes as children progress through puberty, with estradiol and testosterone having important roles in bone growth [ 37 , 38 ]. However, the effects of testosterone are stronger than those of estradiol, as exemplified by the 10% greater bone mass density and the larger and longer bones in post-pubertal males. These sex differences in bone structure provide males with increased fulcrum power, improving jumping, throwing, and other movements requiring explosive actions. The stronger bones also tolerate more trauma and thus males are more resistant to injury. Larger bones in males provide a greater articular surface that, in turn, allows placement of more skeletal muscle. For example, broader shoulders in males allows the build-up of more muscle, thereby increasing upper body strength [ 39 ].

Sex differences in bone shape driven by early life testosterone exposure can affect athletic performance. The most obvious structural difference between males and females is pelvis width, with estradiol driving the wider shape required for childbirth [ 40 ]. A narrower pelvis has a direct impact on the Q angle at the knee joint. The Q angle forms between the quadricep muscles and the patellar tendon and is responsible for generating force during a knee extension. The smaller Q angle of males generates a greater force upon extension [ 41 ]. This has implications for sports that involve standing from a squatting position, kicking a ball, or a pedaling motion. There is also a sex difference in the angle formed between the humerus and ulna at the elbow, with the angle smaller in a male [ 42 ]. The smaller angle for males again allows a greater force upon extension, benefiting sports involving throwing and hitting with bats and rackets.

2.4. Testosterone and the Cardiorespiratory System

Early life testosterone exposure also drives sex differences in the cardiorespiratory system. Females have, on average, a 10–12% smaller lung volume than males, accounting for height, age, and within sex variation [ 43 ]. This smaller lung volume is established within the first few years of life in females due to a lower rate of alveolar multiplication [ 44 , 45 ] and shorter diaphragm that reduces ribcage dimensions [ 46 ]. These anatomical differences therefore drive a lower oxygen uptake capacity in females [ 43 , 44 ]. Females also have a heart size that is about 85% that of males, relative to body size [ 47 ]. This anatomical difference decreases the volume of blood that can be pumped to the body with every contraction of the heart. The larger heart size of males translates to a larger left ventricle and therefore, stroke volume. On average, the stroke volume of females is just one-third that of males. As such, a female’s heart rate must increase proportionally more to achieve a cardiac output necessary to supply active skeletal muscle with enough oxygen.

Active skeletal muscles require the efficient delivery of oxygen, and aerobic capacity is essential for athletic performance. Males have much higher arterial oxygen levels, primarily due to testosterone-regulated synthesis of hemoglobin [ 48 ]. The increased hemoglobin levels coupled with increased lung capacity provides males with a distinct respiratory and oxygen carrying advantage over females. It is consistently reported that hemoglobin concentrations are 12% higher in males than females, and this sex difference in hemoglobin emerges during puberty driven by testosterone [ 48 ]. Administration studies show that testosterone increases hemoglobin levels in a dose-dependent fashion [ 49 ], and medical castration to lower circulating testosterone levels in prostate cancer patients decreases hemoglobin levels [ 50 ].

These effects of testosterone on oxygen carrying capacity, together with the anatomical advantages of male anatomy, help explain the superiority of the male cardiovascular system as it relates to athletic performance. The VO 2 max of an elite male is in the order of 70–85 mL/kg/min, while that of females is 60–75 mL/kg/min; a difference of 15–30% [ 51 ].

3. Male Physiology Cannot Be Reformatted into Female Physiology by Estrogen Therapy

As noted above, the combined effect of testosterone-driven male physiology culminates in greater athletic performance, as evidenced by the dominance of males with respect to World Records and Olympic Gold medals [ 1 , 2 , 3 , 4 , 5 ]. In strength-related sports, world records can differ by 10–30% between males and females [ 1 , 2 , 3 , 4 , 5 ]. As such, to ensure a fair playing field in the female division, a transgender woman athlete should not retain any advantage from her prior testosterone-driven physiology. The evidence below indicates that male physiology cannot be reformatted to female physiology simply by gender-affirming estradiol therapy in a transgender woman training at a high-performance level.

3.1. Difficulties in Achieving Female Levels of Circulating Testosterone in Estrogen-Treated Transwomen

The estrogen treatment regimens used in transgender women aim to lower testosterone levels to within the female range (<1 nmol/L) [ 52 ]. However, hormone therapy alone has met limited success in suppressing testosterone levels, with many transgender women failing to achieve the desired level. In recent studies of transgender women, one quartile failed to achieve any significant suppression [ 53 ] and one-third failed to suppress testosterone levels despite achieving desired estradiol levels [ 54 ]. Another study reported that only 49% of transgender women showed suppressed testosterone concentrations after 6 months or more of estrogen with the addition of antiandrogen therapy [ 55 ]. Notably, Jarin and colleagues show that testosterone levels in transgender women decreased significantly from former male levels, however nearly all participants maintained their testosterone levels above the female range [ 56 ]. Whether elite transwoman athletes experience the same difficulties in suppressing testosterone levels with estrogen therapy has not been reported.

3.2. Estrogen Therapy Does Not Reformat Male-Like Brain Networks

At present, there is little understanding about changes in brain structure and function in transgender individuals. Almost all research in this area has focused on trying to delineate neurobiological pathways that underpin transgenderism, rather on specific areas of the brain related to athletic performance. Overall, current evidence indicates that transgender hormone therapy either has no effect or generates structural and functional changes in the brain that are intermediate between biological males and females [ 57 , 58 , 59 ].

For transgender women, gender-affirming surgery and estrogen therapy have typically, but not always [ 57 ], been shown to reduce brain size and increase ventricular volume towards the parameters measured for biological females [ 60 , 61 , 62 , 63 , 64 ]. While MRI has shown consistent sex differences in functional connectivity within the brain, any alterations following hormonal treatment in transgender individuals remain unclear with studies typically showing no change or the appearance of an intermediate male–female state [ 63 , 64 , 65 , 66 , 67 ]. Notably, the biological male dominance in spatial ability, visual memory tasks, and perception [ 65 , 66 , 67 ] shows no decrease in transwomen after 12 months of estrogen therapy [ 68 ]. A meta-analysis of transgender individuals receiving gender affirming hormone therapy for 3–12 months shows transgender men had a significant enhancement in visuospatial ability (ref. [ 69 ]), with no significant changes for either transgender men or women in verbal memory, verbal reasoning, verbal working memory, computation, or motor coordination. There is an estrogen therapy-related change in transgender women if treated for longer than 12 months with a decreased proneness towards anger and aggressiveness [ 70 ].

While more research is required for definitive answers, the current data demonstrates that estrogen therapy in transwomen can drive some brain structures towards that of the biological female [ 71 , 72 , 73 ] but does not do so quickly and appears to not reformat the sex-typical male brain responses into a female-like brain. This is compatible with the concept that both the in utero and perinatal surges of testosterone secretion occurring in males drive permanent sex differences in brain structure and function which are apparent in young boys before puberty [ 74 ]. Human spatial ability, for example, appears beneficially affected by prenatal androgens [ 75 , 76 ], with second trimester testosterone levels correlated positively in biological females and negatively in biological males at age 7 [ 77 ].

3.3. Estrogen Therapy Does Not Reformat Male Skeletal Architecture but Does Decrease Muscle Mass

As there is a dose-dependent relationship between testosterone and muscle mass [ 32 , 33 , 34 ], lowering circulating testosterone levels from an average male level to <10 nmol/L should decrease muscle mass in a transwoman. Indeed, studies report muscle mass loss, with a 5% loss for lower limb mass or a 9.4% for total muscle mass loss after 12 months of estrogen therapy [ 78 , 79 ]. The loss of muscle mass did not, however, associate with loss of strength or muscle fiber density or performance [ 79 ]. For example, prior to transitioning, transwoman airforce personnel recorded a 12% faster time for a 1.5 mile run than their biological female peers that declined to a 9% difference after 2–2.5 years on estrogen therapy [ 80 ]. This decline in performance is similar to a self-reported study of running times in transwomen in the 12 months after transitioning [ 81 ]. While such results represent a marked decrease in performance, the running times of the transwomen group remain significantly higher than those of the biological women [ 80 ], despite prolonged estrogen therapy. The performance benefit of prior testosterone exposure for the running test is likely attributable to not only muscle mass but male skeletal architecture that, as discussed earlier includes longer limbs, a narrower pelvic structure and a greater cardiorespiratory size—all of which will not respond to changes in circulating testosterone levels in adulthood. Further to this, studies show that there is no bone mass loss in transwomen after 28–63 months of estrogen therapy [ 82 ].

As discussed earlier, sex differences in muscle mass in elite athletes can be 50–75% [ 30 ] in favor of males, thus the decrease of 5–10% reported in studies of transwomen after 1–2 years of estrogen therapy will most likely provide, at most, a modest reformatting of male muscle strength in the transwoman athlete. Further evidence to support maintenance of muscle mass in the face of lowered testosterone levels is observed in prostate cancer patients. Such patients are on androgen-deprivation therapy for extended periods to lower testosterone levels to very low levels (i.e., within the female range) but only report a small loss (2–4%) in muscle mass over 12 months [ 83 ]. Notably, this effect can be mitigated with an exercise training program [ 79 , 84 , 85 ]. Therefore, it follows that a transwoman athlete following a high-performance training program enabling competitiveness at an elite level throughout the 12-month estrogen therapy transition period could similarly mitigate muscle mass loss.

The difficulty of reformatting muscle physiology to female levels in transwomen likely results from their life-long exposure to testosterone prior to transitioning and prior levels of exercise as a male. Increased muscle mass arises from hypertrophy of individual muscle fibers in response to enhanced protein synthesis within the cells. Muscle cells recruit nuclei from nearly helper satellite cells to increase protein synthesis and allow muscle cell hypertrophy [ 86 , 87 , 88 , 89 ]. The most important stimulus for muscle hypertrophy is exercise and thus, muscles subjected to overload exercise recruit nuclei. If the muscle then undergoes a period of rest, the muscle cell will atrophy back to its baseline size but will retain the nuclei acquired during the hypertrophic phase. In humans, nuclei numbers are very stable and may even be permanent [ 90 ]. When these cells with higher numbers of nuclei are again subjected to overload exercise, the cells can quickly ramp up protein synthesis and hypertrophy. Thus, muscle cell nuclei number represents a form of “muscle memory” that is a functionally important indicator of prior strength and explains how previous exercise improves the ability to regain muscle mass later in life, even after long sedentary periods [ 91 , 92 ].

Mouse studies have shown that testosterone administration for 2 weeks significantly increased muscle cell hypertrophy and generated an increase in muscle cell nuclei number that was maintained for the next 8 weeks. Mice were then subjected to overload training and those animals that had been treated with testosterone showed a 3-fold increase in muscle hypertrophy compared to controls [ 88 ].

Muscle memory is, therefore, a critical factor when considering the physiology of transwoman athletes. Prior to transitioning, the post-pubertal exposure to high androgen levels, relative to a biological female, would increase muscle cell nuclei number [ 93 ], a long-term benefit that is not quickly, if ever, reversed. This androgen-induced muscle memory effect has been used to argue that a two-year sanction from elite competition is not sufficient for those athletes found to have consumed exogenous androgens because of the potential on-going athletic performance advantage [ 94 , 95 ].

3.4. Estrogen Therapy and Effects on the Cardiorespiratory System

The physiological parameter that will be affected most by estrogen therapy is VO 2 max or maximum aerobic performance. Due to the dependence of VO 2 max on hemoglobin levels, and the relationship between testosterone and hemoglobin, reduced testosterone will decrease VO 2 max . Importantly, hemoglobin is sensitive to testosterone even at low concentrations [ 96 ], with dose-dependent increases measured in females within the 0–4 nmol/L range [ 96 ]. Males on androgen-deprivation therapy show a significant 9% drop in hemoglobin levels after 12 months, with a further variable decline by 12.8–29% after 24 months [ 97 ]. This decrease in hemoglobin will likely decrease maximal aerobic performance. The hemoglobin response to testosterone concentrations, whether increasing or decreasing, occurs within weeks [ 98 ], thus, if the hemoglobin levels are to remain lowered in transfemale athletes, circulating testosterone levels must remain consistently reduced. As discussed above, achieving testosterone suppression to very low levels in transwomen can be difficult [ 53 , 54 , 55 , 56 ], where nearly all transwomen involved in reported studies failed to achieve or maintain testosterone levels in the biological female range, which was consummate with a higher hemoglobin level than that of biological females [ 56 ].

While hemoglobin levels respond closely to circulating testosterone levels, other cardiorespiratory system parameters are unlikely to be impacted significantly by estrogen therapy. For example, sex differences in lung size and alveolar numbers, total heart size, left ventricular size, stroke volume, and subsequent cardiac output will not be changed significantly. All of these parameters are defined by anatomical structures that were programmed by early life and early pubertal exposure to testosterone.

4. Conclusions

Testosterone drives much of the enhanced athletic performance of males through in utero, early life, and adult exposure. Many anatomical sex differences driven by testosterone are not reversible. Hemoglobin levels and muscle mass are sensitive to adult life testosterone levels, with hemoglobin being the most responsive. Studies in transgender women, and androgen-deprivation treated cancer patients, show muscle mass is retained for many months, even years, and that co-comittant exercise mitigates muscle loss. Given that sports are currently segregated into male and female divisions because of superior male athletic performance, and that estrogen therapy will not reverse most athletic performance parameters, it follows that transgender women will enter the female division with an inherent advantage because of their prior male physiology.

The current IOC regulations allow transwomen athletes to compete if testosterone levels have been lowered to <10 nmol/L for 12 months prior to competition. While this begins to address the advantageous effects of circulating testosterone on athletic performance, it does not take into account the advantage afforded by testosterone exposure prior to transitioning. The existing data suggests that lowering testosterone to less than 10 nmol/L for 12 months decreases muscle mass but not to biological female levels and despite the decrease in mass, muscle strength can be maintained, especially if concurrently exercising. Estrogen therapy does not affect most of the anatomical structures in the biological male that provide a physiological benefit. Hemoglobin levels are lowered by estrogen therapy, and consequently, maximum aerobic effort may be lower, but this parameter will only be manifested if testosterone levels are suppressed to levels within the biological female range and maintained for extended periods of time. Reported studies show it is difficult to continuously suppress testosterone in transgender women. Given that the percentage difference between medal placings at the elite level is normally less than 1%, there must be confidence that an elite transwoman athlete retains no residual advantage from former testosterone exposure, where the inherent advantage depending on sport could be 10–30%. Current scientific evidence can not provide such assurances and thus, under abiding rulings, the inclusion of transwomen in the elite female division needs to be reconsidered for fairness to female-born athletes.

Acknowledgments

The author acknowledges the discussions with Lynley Anderson and Taryn Knox (University of Otago, New Zealand) to help provide a balance of science versus sociocultural views during the writing of this manuscript.

Funding Statement

This research received no external funding.

Institutional Review Board Statement

Informed consent statement, data availability statement, conflicts of interest.

The author declares no conflict of interest.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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