Medicine:Transgender hormone therapy

Short description: Gender-affirming medical treatment

Transgender hormone therapy, also called hormone replacement therapy (HRT) or gender-affirming hormone therapy (GAHT), is a form of hormone therapy in which sex hormones and other hormonal medications are administered to transgender or gender nonconforming individuals for the purpose of more closely aligning their secondary sexual characteristics with their gender identity. This form of hormone therapy is given as one of two types, based on whether the goal of treatment is masculinization or feminization:

• Masculinizing hormone therapy – for transgender men or transmasculine people; consists of androgens and antiestrogens.
• Feminizing hormone therapy – for transgender women or transfeminine people; consists of estrogens with or without antiandrogens.

Eligibility for transgender hormone therapy may be concluded by assessing a patient for gender dysphoria or persistent gender incongruence, though many medical institutions now used an informed consent model. This model ensures patients are informed of the procedure process, including possible benefits and risks, while removing many of the historical barriers needed to start hormone therapy. Treatment guidelines for therapy have been developed by several medical associations.

Some intersex people may also undergo hormone therapy, either starting in childhood to confirm the sex they were assigned at birth, or later in order to align their sex with their gender identity. Non-binary people may also engage in hormone therapy in order to achieve a desired balance of sex hormones or to help align their bodies with their gender identities. Many transgender people obtain hormone therapy from a licensed health care provider and others obtain and self-administer hormones.

Requirements

The formal requirements to begin gender-affirming hormone therapy vary widely depending on geographic location and specific institution. Gender affirming hormones can be prescribed by a wide range of medical providers including, but not limited to, primary care physicians, endocrinologists, and obstetrician-gynecologists.

Historically, many health centers required a psychiatric evaluation and/or a letter from a therapist before beginning therapy. Many centers now use an informed consent model that does not require any routine formal psychiatric evaluation but instead focuses on reducing barriers to care by ensuring a person can understand the risks, benefits, alternatives, unknowns, limitations, and risks of no treatment. Some LGBT health organizations (notably Chicago's Howard Brown Health Center and Planned Parenthood) advocate for this type of informed consent model.

The Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People (SOC) require that patients seeking gender-affirmation hormone therapy be evaluated for gender dysphoria by either a mental health professional or hormone provider who is qualified in the area of transgender care. The Standards also require that the patient give informed consent, in other words, that they consent to the treatment after being fully informed of the risks involved. Before beginning gender-affirming hormone therapy, the patient must be evaluated for significant medical and mental health concerns. If present, these must be addressed and reasonably well-controlled.

The World Professional Association for Transgender Health (WPATH) Standards of Care, 7th edition, note that both of these approaches to care are appropriate.

Gender dysphoria

Many international guidelines and institutions require persistent, well-documented gender dysphoria as a pre-requisite to starting gender-affirmation therapy. Gender dysphoria refers to the psychological discomfort or distress that an individual can experience if their sex assigned at birth is incongruent with that person's gender identity. Signs of gender dysphoria can include comorbid mental health stressors such as depression, anxiety, low self-esteem, and social isolation. Not all gender nonconforming individuals experience gender dysphoria.

Treatment options

Guidelines

The World Professional Association for Transgender Health (WPATH) and the Endocrine Society formulated guidelines that created a foundation for health care providers to care for transgender patients. UCSF guidelines are also used. There is no generally agreed-upon set of guidelines, however.

Delaying puberty in adolescents

Tanner Stages for Female Sexual Characteristics

Tanner Stages for Male Sexual Characteristics

Adolescents experiencing gender dysphoria may opt to undergo puberty-suppressing hormone therapy at the onset of puberty. The Standards of Care set forth by WPATH recommend individuals pursuing puberty-suppressing hormone therapy wait until at least experiencing Tanner Stage 2 pubertal development. Tanner Stage 2 is defined by the appearance of scant pubic hair, breast bud development, and/or slight testicular growth. WPATH classifies puberty-suppressing hormone therapy as a "fully reversible" intervention. Delaying puberty allows individuals more time to explore their gender identity before deciding on more permanent interventions and prevents the physical changes associated with puberty.

The preferred puberty-suppressing agent for both individuals assigned male at birth and individuals assigned female at birth is a GnRH Analogue. This approach temporarily shuts down the Hypothalamic-Pituitary-Gonadal (HPG) Axis, which is responsible for the production of hormones (estrogen, testosterone) that cause the development of secondary sexual characteristics in puberty.

Feminizing hormone therapy

Feminizing hormone therapy is typically used by transgender women, who desire the development of feminine secondary sex characteristics. Individuals who identify as non-binary may also opt-in for feminizing hormone treatment to better align their body with their desired gender expression. Feminizing hormone therapy usually includes medication to suppress testosterone production and induce feminization. Types of medications include estrogens, antiandrogens (testosterone blockers), and progestogens. Most commonly, an estrogen is combined with an antiandrogen to suppress and block testosterone. This allows for demasculinization and promotion of feminization and breast development. Estrogens are administered in various modalities including injection, transdermal patch, and oral tablets.

The desired effects of feminizing hormone therapy focus on the development of feminine secondary sex characteristics. These desired effects include: breast tissue development, redistribution of body fat, decreased body hair, reduction of muscle mass, and more. The table below summarizes some of the effects of feminizing hormone therapy in transgender women:

Effects of feminizing hormone therapy

Effect	Time to expected onset of effect	Time to expected maximum effect	Permanency if hormone therapy is stopped
Breast development and nipple/areolar enlargement	2–6 months	1–5 years	Permanent
Thinning/slowed growth of facial/body hair	4–12 months	>3 years	Reversible
Cessation/reversal of male-pattern scalp hair loss	1–3 months	1–2 years	Reversible
Softening of skin/decreased oiliness and acne	3–6 months	Unknown	Reversible
Redistribution of body fat in a feminine pattern	3–6 months	2–5 years	Reversible
Decreased muscle mass/strength	3–6 months	1–2 years	Reversible
Widening and rounding of the pelvis	Unspecified	Unspecified	Permanent
Changes in mood, emotionality, and behavior	Unspecified	Unspecified	Reversible
Decreased sex drive	1–3 months	Temporary	Reversible
Decreased spontaneous/morning erections	1–3 months	3–6 months	Reversible
Erectile dysfunction and decreased ejaculate volume	1–3 months	Variable	Reversible
Decreased sperm production/fertility	Unknown	>3 years	Reversible or permanent
Decreased testicle size	3–6 months	2–3 years	Unknown
Decreased penis size	None	Not applicable	Not applicable
Decreased prostate gland size	Unspecified	Unspecified	Unspecified
Voice changes	None	Not applicable	Not applicable
Footnotes and sources Footnotes: Sources: Guidelines: Reviews/book chapters: Studies:

Masculinizing hormone therapy

Masculinizing hormone therapy is typically used by transgender men, who desire the development of masculine secondary sex characteristics. Masculinizing hormone therapy usually includes testosterone to produce masculinization and suppress the production of estrogen. Treatment options include oral, parenteral, subcutaneous implant, and transdermal (patches, gels). Dosing is patient-specific and is discussed with the physician. The most commonly prescribed methods are intramuscular and subcutaneous injections. This dosing can be weekly or biweekly depending on the individual patient.

Unlike feminizing hormone therapy, individuals undergoing masculinizing hormone therapy do not usually require additional hormone suppression such as estrogen suppression. Therapeutic doses of testosterone are usually sufficient to inhibit the production of estrogen to desired physiologic levels.

The desired effects of masculinizing hormone therapy focus on the development of masculine secondary sex characteristics. These desired effects include: increased muscle mass, development of facial hair, voice deepening, increase and thickening of body hair, and more.

Effects of masculinizing hormone therapy

Reversible Changes	Irreversible Changes
Increased libido	Deepening of voice
Redistribution of body fat	Growth of facial/body hair
Cessation of ovulation/menstruation	Male-pattern baldness
Increased muscle mass	Enlargement of clitoris
Increased perspiration	Growth spurt/closure of growth plates
Acne	Breast atrophy
Increased RBC count

Safety

Hormone therapy for transgender individuals has been shown in medical literature to be generally safe, when supervised by a qualified medical professional. There are potential risks with hormone treatment that will be monitored through screenings and lab tests such as blood count (hemoglobin), kidney and liver function, blood sugar, potassium, and cholesterol. Taking more medication than directed may lead to health problems such as increased risk of cancer, heart attack from thickening of the blood, blood clots, and elevated cholesterol.

Feminizing hormone therapy

The Standards of Care published by the World Professional Association for Transgender Health (WPATH) summarize many of the risks associated with feminizing hormone therapy (outlined below). For more in-depth information on the safety profile of estrogen-based feminizing hormone therapy visit the feminizing hormone therapy page.

Likely Increased Risk	Possible Increased Risk	Inconclusive/No Increased Risk
Venous thromboembolic disease	Type 2 diabetes	Breast cancer
Cardiovascular disease	Hypertension	Prostate cancer
Hypertriglyceridemia	Hyperprolactinaemia
Gallstones	Osteoporosis
Hyperkalemia
Cerebrovascular disease
Polyuria (or dehydration)
Meningioma

Masculinizing hormone therapy

The Standards of Care published by the World Professional Association for Transgender Health (WPATH) summarize many of the risks associated with masculinizing hormone therapy (outlined below). For more in-depth information on the safety profile of testosterone-based masculinizing hormone therapy visit the masculinizing hormone therapy page.

Summary of Risks of Testosterone Therapy

Likely Increased Risk	Possible Increased Risk	Inconclusive/No Increased Risk
Polycythemia	Type 2 diabetes	Osteoporosis
Weight gain		Breast cancer
Acne		Ovarian cancer
Pattern hair loss		Uterine cancer
Hypertension		Cervical cancer
Sleep apnea
Decreased HDL cholesterol
Decreased LDL cholesterol
Cardiovascular disease
Hypertriglyceridemia

Fertility consideration

Transgender hormone therapy may limit fertility potential. Should a transgender individual choose to undergo sex reassignment surgery, their fertility potential is lost completely. Before starting any treatment, individuals may consider fertility issues and fertility preservation. Options include semen cryopreservation, oocyte cryopreservation, and ovarian tissue cryopreservation.

A study presented at ENDO 2019 (the Endocrine Society's conference) shows that even after one year of treatment with testosterone, a transgender man can preserve his fertility potential.

Treatment eligibility

Many providers use informed consent, whereby someone seeking hormone therapy can sign a statement of informed consent and begin treatment without much gatekeeping. For other providers, eligibility is determined using major diagnostic tools such as ICD-11 or the Diagnostic and Statistical Manual of Mental Disorders (DSM) to classify a patient with gender dysphoria. Psychiatric conditions can commonly accompany or present similar to gender incongruence and gender dysphoria. For this reason, patients are assessed using DSM-5 criteria or ICD-11 criteria in addition to screening for psychiatric disorders. The Endocrine Society requires physicians that diagnose gender dysphoria and gender incongruence to be trained in psychiatric disorders with competency in ICD-11 and DSM-5. The healthcare provider should also obtain a thorough assessment of the patient's mental health and identify potential psychosocial factors that can affect therapy.

WPATH Standards of Care

The WPATH Standards of Care, most recently published in 2022, outlines a series of guidelines which should be met before a patient should be allowed transgender hormone replacement therapy:

• Gender incongruence is marked and sustained
• Patient meets diagnostic criteria for gender incongruence prior to gender-affirming hormone treatment in regions where a diagnosis is necessary to access health care
• Patient has capacity to consent to hormone therapy treatment
• Other possible causes of apparent gender incongruence have been identified and excluded
• Mental health and physical conditions that could negatively impact the outcome of treatment have been assessed
• Understands the effect of gender-affirming hormone treatment on reproduction and they have explored reproductive options

Readiness

Some organizations – but fewer than in the past – require that patients spend a certain period of time living in their desired gender role before starting hormone therapy. This period is sometimes called real-life experience (RLE). The Endocrine Society stated in 2009 that individuals should either have a documented three months of RLE or undergo psychotherapy for a period of time specified by their mental health provider, usually a minimum of three months.

Transgender and gender non-conforming activists, such as Kate Bornstein, have asserted that RLE is psychologically harmful and is a form of "gatekeeping", effectively barring individuals from transitioning for as long as possible, if not permanently.

Accessibility

Gender-affirming care is health care that affirms people to live authentically in their genders, no matter the gender they were assigned at birth or the path their gender affirmation (or transition) takes. It allows each person to seek only the changes or medical interventions they desire to affirm their own gender identity, and hormone therapy ("HRT" or gender-affirming hormone therapy) may be a part of that.

Some transgender people choose to self-administer hormone replacement medications, often because doctors have too little experience in this area, or because no doctor is available. Others self-administer because their doctor will not prescribe hormones without a letter from a psychotherapist stating that the patient meets the diagnostic criteria and is making an informed decision to transition. Many therapists require at least three months of continuous psychotherapy and/or real-life experience before they will write such a letter. Because many individuals must pay for evaluation and care out-of-pocket, costs can be prohibitive.

Access to medication can be poor even where health care is provided free. In a patient survey conducted by the United Kingdom 's National Health Service in 2008, 5% of respondents acknowledged resorting to self-medication, and 46% were dissatisfied with the amount of time it took to receive hormone therapy. The report concluded in part: "The NHS must provide a service that is easy to access so that vulnerable patients do not feel forced to turn to DIY remedies such as buying drugs online with all the risks that entails. Patients must be able to access professional help and advice so that they can make informed decisions about their care, whether they wish to take the NHS or private route without putting their health and indeed their lives in danger." Self-administration of hormone replacement medications without medical supervision may have untoward health effects and risks.

A number of private companies have attempted to increase accessibility for hormone replacement medications and help transgender people navigate the complexities of access to treatment.

See also

• Hormone therapy
• Sex reassignment surgery
• Real-life experience (transgender)

References

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| name = Androgens and antiandrogens
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(incl. AAS)

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AR agonists

Testosterone derivatives: Androstenediol dipropionate Boldenone undecylenate Clostebol Clostebol acetate Clostebol caproate Clostebol propionate Cloxotestosterone acetate Prasterone (dehydroepiandrosterone, DHEA) Prasterone enanthate (DHEA enanthate) Prasterone sulfate (DHEA sulfate) Quinbolone Testosterone# Testosterone esters (e.g., testosterone cypionate, testosterone enanthate]], testosterone propionate]], testosterone undecanoate]], testosterone ester mixture]]s (Deposterona, Omnadren, Sustanon, Testoviron Depot)) Dihydrotestosterone derivatives: Androstanolone (stanolone, dihydrotestosterone, DHT) Androstanolone esters Bolazine capronate Drostanolone propionate (dromostanolone propionate) Epitiostanol Mepitiostane Mesterolone Metenolone acetate (methenolone acetate) Metenolone enanthate (methenolone enanthate) Stenbolone acetate 19-Nortestosterone derivatives: Bolandiol dipropionate Nandrolone esters (e.g., nandrolone decanoate, nandrolone phenylpropionate) Norclostebol Norclostebol acetate Oxabolone cipionate (oxabolone cypionate) Trenbolone acetate Trenbolone hexahydrobenzylcarbonate (trenbolone cyclohexylmethylcarbonate) 17α-Alkylated testosterone derivatives: Bolasterone Calusterone Chlorodehydromethyltestosterone (CDMT) Fluoxymesterone Formebolone Metandienone (methandienone, methandrostenolone) Methandriol (methylandrostenediol) Methandriol bisenanthoyl acetate Methandriol dipropionate Methandriol propionate Methyltestosterone Methyltestosterone 3-hexyl ether Oxymesterone Penmesterol Tiomesterone (thiomesterone) 17α-Alkylated dihydrotestosterone derivatives: Androisoxazole Furazabol Mebolazine (dimethazine) Mestanolone Oxandrolone Oxymetholone Stanozolol 17α-Alkylated 19-nortestosterone derivatives: Ethylestrenol Mibolerone Norethandrolone Normethandrone (methylestrenolone, normethisterone) Propetandrol (propethandrol) 17α-Vinyltestosterone derivatives: Norvinisterone (vinylnortestosterone) 17α-Ethynyltestosterone derivatives: Danazol Gestrinone Progestins (e.g., ethisterone (ethynyltestosterone), levonorgestrel, norgestrel, norethisterone (norethindrone), [[Chemistry:Lynestrlynestrenol, Norgestrienone|norgestrienone]]) Tibolone Progesterone derivatives: Medroxyprogesterone acetate

Progonadotropins

Antiestrogens (e.g., tamoxifen, Chemistry:Clomifene

| group2 = Antiandrogens
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  | group1 = AR antagonists
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• Steroidal: Abiraterone acetate
• Canrenone
• Chlormadinone acetate
• Cyproterone acetate
• Delmadinone acetate
• Dienogest
• Drospirenone
• Medrogestone
• Megestrol acetate
• Nomegestrol acetate
• Osaterone acetate
• Oxendolone
• Potassium canrenoate
• Spironolactone

• Nonsteroidal: Apalutamide
• Bicalutamide
• Cimetidine
• Darolutamide
• Enzalutamide
• Flutamide
• Ketoconazole
• Nilutamide
• Seviteronel^†
• Topilutamide (fluridil)

  | group2 = Steroidogenesis
inhibitors

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5α-Reductase	Alfatradiol Dutasteride Epristeride Finasteride Saw palmetto extract
Others	Abiraterone acetate Aminoglutethimide Bifluranol Cyproterone acetate Flutamide Ketoconazole Nilutamide Seviteronel† Spironolactone

  | group3 = Antigonadotropins
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• D₂ receptor antagonists (prolactin releasers) (e.g., domperidone, metoclopramide, risperidone, haloperidol, chlorpromazine, sulpiride)
• Estrogens (e.g., bifluranol, [[diethylstilbestrol, estradiol, estradiol esters, ethinylestradiol, ethinylestradiol sulfonate, paroxypropione)
• GnRH agonists (e.g., leuprorelin)
• GnRH antagonists (e.g., cetrorelix)
• Progestogens (incl., chlormadinone acetate, [[cyproterone acetate, hydroxyprogesterone caproate, gestonorone caproate, [[Chemistry:Medroxyprogesterone medroxyprogesterone acetate, Chemistry:Megestrol acetate|megestrol acetate]])

  | group4 = Others
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• Androstenedione immunogens: Androvax (androstenedione albumin)
• Ovandrotone albumin (Fecundin)

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• ^#WHO-EM
• ^‡Withdrawn from market
• Clinical trials:
  • ^†Phase III
  • ^§Never to phase III

See also

Androgen receptor modulators

Estrogens and antiestrogens

Progestogens and antiprogestogens

List of androgens/anabolic steroids

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