Transgender hormone therapy

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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:

Contents

Eligibility for transgender hormone therapy may require an assessment for gender dysphoria or persistent gender incongruence; or many medical institutions now use an informed consent model, which 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.

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. [1] Many transgender people obtain hormone therapy from a licensed health care provider and others obtain and self-administer hormones.

History

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 gynecologists. [2] Requirements generally include a minimum age; according to the Endocrine Society, there has been little research on taking cross-sex hormones before the age of about 14. [3]

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. [4] Some LGBT health organizations (notably Chicago's Howard Brown Health Center [5] and Planned Parenthood [6] ) advocate for this type of informed consent model.

The World Professional Association for Transgender Health (WPATH) Standards of Care, 7th edition, note that both of these approaches to care are appropriate. [2]

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. [7] Signs of gender dysphoria can include comorbid mental health stressors such as depression, anxiety, low self-esteem, and social isolation. [8] Not all gender nonconforming individuals experience gender dysphoria, and measuring a person's gender dysphoria is critical when considering medical intervention for gender nonconformity. [9]

Treatment options

Guidelines

For transgender youth, the Dutch protocol existed as among the earlier guidelines for hormone therapy by delaying puberty until age 16. [10] [11] The World Professional Association for Transgender Health (WPATH) and the Endocrine Society later formulated guidelines that created a foundation for health care providers to care for transgender patients. [12] [13] UCSF guidelines are also sometimes used. [4] There is no generally agreed-upon set of guidelines, however. [14]

Delaying puberty in adolescents

Tanner Stages for Female Sexual Characteristics Tanner scale-female.svg
Tanner Stages for Female Sexual Characteristics
Tanner Stages for Male Sexual Characteristics Tanner scale-male.svg
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. [7] Tanner Stage 2 is defined by the appearance of scant pubic hair, breast bud development, and/or slight testicular growth. [15] 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. [7]

The preferred puberty-suppressing agent for both individuals assigned male at birth and individuals assigned female at birth is a GnRH Analogue. [7] 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. [16]

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. [17] Feminizing hormone therapy usually includes medication to suppress testosterone production and induce feminization. Types of medications include estrogens, antiandrogens (testosterone blockers), and progestogens. [18] Most commonly, an estrogen is combined with an antiandrogen to suppress and block testosterone. [19] This allows for demasculinization and promotion of feminization and breast development. Estrogens are administered in various modalities including injection, transdermal patch, and oral tablets. [19]

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. [19] The table below summarizes some of the effects of feminizing hormone therapy in transgender women:

Effects of feminizing hormone therapy
EffectTime to expected
onset of effect [lower-alpha 1] 		Time to expected
maximum effect [lower-alpha 1] [lower-alpha 2] 		Permanency if hormone
therapy is stopped
Breast development and nipple/areolar enlargement2–6 months1–5 yearsPermanent
Thinning/slowed growth of facial/body hair 4–12 months>3 years [lower-alpha 3] Reversible
Cessation/reversal of male-pattern scalp hair loss 1–3 months1–2 years [lower-alpha 4] Reversible
Softening of skin/decreased oiliness and acne 3–6 monthsUnknownReversible
Redistribution of body fat in a feminine pattern 3–6 months2–5 yearsReversible
Decreased muscle mass/strength 3–6 months1–2 years [lower-alpha 5] Reversible
Widening and rounding of the pelvis [lower-alpha 6] UnspecifiedUnspecifiedPermanent
Changes in mood, emotionality, and behavior UnspecifiedUnspecifiedReversible
Decreased sex drive 1–3 monthsTemporary [20] Reversible
Decreased spontaneous/morning erections 1–3 months3–6 monthsReversible
Erectile dysfunction and decreased ejaculate volume 1–3 monthsVariableReversible
Decreased sperm production/fertility Unknown>3 yearsReversible or permanent [lower-alpha 7]
Decreased testicle size3–6 months2–3 yearsUnknown
Decreased penis sizeNone [lower-alpha 8] Not applicableNot applicable
Decreased prostate gland sizeUnspecifiedUnspecifiedUnspecified
Voice changesNone [lower-alpha 9] Not applicableNot applicable
Footnotes and sources
Footnotes:
  1. 1 2 Estimates represent published and unpublished clinical observations.
  2. ↑ Time at which further changes are unlikely at maximum maintained dose. Maximum effects vary widely depending on genetics, body habitus, age, and status of gonad removal. Generally, older individuals with intact gonads may have less feminization overall.
  3. ↑ Complete removal of male facial and body hair requires electrolysis, laser hair removal, or both. Temporary hair removal can be achieved with shaving, epilating, waxing, and other methods.
  4. ↑ Familial scalp hair loss may occur if estrogens are stopped.
  5. ↑ Varies significantly depending on the amount of physical exercise.
  6. ↑ Occurs only in individuals of pubertal age who have not yet completed epiphyseal closure.
  7. ↑ Additional research is needed to determine permanency, but a permanent impact of estrogen therapy on sperm quality is likely and sperm preservation options should be counseled on and considered before initiation of therapy.
  8. ↑ Conflicting reports, with none reported observed in transgender women but significant albeit minor reduction of penis size reported in men with prostate cancer on androgen deprivation therapy. [21] [22] [23] [24]
  9. ↑ Treatment by speech pathologists for voice training is effective.
Sources:Guidelines: [25] [7] [26] Reviews/book chapters: [27] [28] [29] [30] Studies: [31] [32]

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. [33] Treatment options include oral, subcutaneous injections or implant, and transdermal (patches, gels). Dosing is patient-specific, depending on the patient's rate of metabolism, and is discussed with the physician. [34] The most commonly prescribed methods are intramuscular and subcutaneous injections.[ citation needed ] This dosing can be daily, weekly or biweekly depending on the route of administration and the individual patient. [34]

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. [16]

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. [35]

Effects of masculinizing hormone therapy [4] [7]
Reversible ChangesIrreversible Changes
Increased libidoDeepening of voice
Redistribution of body fatGrowth of facial/body hair
Cessation of ovulation/menstruationMale-pattern baldness
Increased muscle massEnlargement of clitoris
Increased perspirationGrowth spurt/closure of growth plates
AcneBreast atrophy
Increased red blood cell count

Safety

Hormone therapy for transgender individuals has been shown in medical literature to be generally safe, when supervised by a qualified medical professional. [36] 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. [34] [18] 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. [34] [37]

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). [7] For more in-depth information on the safety profile of estrogen-based feminizing hormone therapy visit the feminizing hormone therapy page.

Summary of Risks of Estrogen Therapy [38]
Likely Increased RiskPossible Increased RiskInconclusive/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) [lower-alpha 1]
Meningioma [lower-alpha 2]
  1. ↑ Only present in individuals taking spironolactone
  2. ↑ Only present in individuals taking cyproterone

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). [7] 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 [38]
Likely Increased RiskPossible Increased RiskInconclusive/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. [39] Should a transgender individual choose to undergo gender-affirming surgery, their fertility potential is lost completely. [40] Before starting any treatment, individuals may consider fertility issues and fertility preservation. Options include semen cryopreservation, oocyte cryopreservation, and ovarian tissue cryopreservation. [39] [40]

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. [41]

Fake products

Some online scammers have been targeting trans consumers with products that do not contain any hormones or contain ones that are opposite of what is advertised. This can happen when legislations outlaw or restrict access to treatments by legitimate medical professionals. [42]

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. 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. [43]

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 gender-affirming hormone therapy: [38]

The WPATH standards of care distinguish between gender-affirming hormone therapy, and hormone replacement therapy, with the latter referring to the replacement of endogenous hormones after a gonadectomy to prevent cardiovascular and musculoskeletal issues. [38]

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).

In Sweden, for instance, patients seeking to access gender affirming healthcare must first undergo extended evaluations with psychiatric professionals, during which they must - without any form of medical transition - successfully live for one full year as their desired gender in all professional, social, and personal matters. Gender clinics are recommended to provide patients with wigs and breast prostheses for the endeavor. The evaluation additionally involves, if possible, meetings with family members and/or other individuals close to the patient. Patients may be denied care for any number of "psychosocial dimensions", including their choice of job or their marital status. [44] [45]

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. [46]

In September 2022, the World Professional Association for Transgender Health (WPATH) Standards of Care for the Health of Transgender and Gender Diverse People (SOC) Version 8 were released and removed the requirement of RLE for all gender-affirming treatments, including gender-affirming surgery. [47]

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. [48]

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 an approval letter from a psychotherapist. Many therapists require extended periods 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.[ citation needed ]

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." [49] Self-administration of cross-gender hormones without medical supervision may have untoward health effects and risks. [50]

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.[ citation needed ]

See also

Related Research Articles

Gender dysphoria (GD) is the distress a person experiences due to a mismatch between their gender identity—their personal sense of their own gender—and their sex assigned at birth. The term replaced the previous diagnostic label of gender identity disorder (GID) in 2013 with the release of the diagnostic manual DSM-5. The condition was renamed to remove the stigma associated with the term disorder.

Gender-affirming surgery is a surgical procedure, or series of procedures, that alters a person's physical appearance and sexual characteristics to resemble those associated with their identified gender. The phrase is most often associated with transgender health care and intersex medical interventions, although many such treatments are also pursued by cisgender and non-intersex individuals. It is also known as sex reassignment surgery, gender confirmation surgery, and several other names.

The World Professional Association for Transgender Health (WPATH), formerly the Harry Benjamin International Gender Dysphoria Association (HBIGDA), is a professional organization devoted to the understanding and treatment of gender identity and gender dysphoria, and creating standardized treatment for transgender and gender variant people. WPATH was founded in September 1979 by endocrinologist and sexologist Harry Benjamin, with the goal of creating an international community of professionals specializing in treating gender variance.

The Standards of Care for the Health of Transgender and Gender Diverse People (SOC) is an international clinical protocol by the World Professional Association for Transgender Health (WPATH) outlining the recommended assessment and treatment for transgender and gender-diverse individuals across the lifespan including social, hormonal, or surgical transition. It often influences clinicians' decisions regarding patients' treatment. While other standards, protocols, and guidelines exist – especially outside the United States – the WPATH SOC is the most widespread protocol used by professionals working with transgender or gender-variant people.

<span class="mw-page-title-main">Gender transition</span> Changing gender presentation to accord with gender identity

Gender transition is the process of affirming and expressing one's internal sense of gender, as opposed to the gender assigned to them at birth. There are two major facets of gender transitioning: a social transition, and a medical transition; almost all transgender people will socially transition, and most will undergo some degree of medical transition.

Pediatric endocrinology is a medical subspecialty dealing with disorders of the endocrine glands, such as variations of physical growth and sexual development in childhood, diabetes and many more.

<span class="mw-page-title-main">Triptorelin</span> GnRH-agonist

Triptorelin, sold under the brand name Decapeptyl among others, is a medication that acts as an agonist analog of gonadotropin-releasing hormone, repressing expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

<span class="mw-page-title-main">Gonadotropin-releasing hormone antagonist</span> Class of medications

Gonadotropin-releasing hormone antagonists are a class of medications that antagonize the gonadotropin-releasing hormone receptor and thus the action of gonadotropin-releasing hormone (GnRH). They are used in the treatment of prostate cancer, endometriosis, uterine fibroids, female infertility in assisted reproduction, and for other indications.

Gender dysphoria in children (GD), also known as gender incongruence of childhood, is a formal diagnosis for children who experience significant discontent due to a mismatch between their assigned sex and gender identity. The diagnostic label gender identity disorder in children (GIDC) was used by the Diagnostic and Statistical Manual of Mental Disorders (DSM) until it was renamed gender dysphoria in children in 2013 with the release of the DSM-5. The diagnosis was renamed to remove the stigma associated with the term disorder.

Gender incongruence is the state of having a gender identity that does not correspond to one's sex assigned at birth. This is experienced by people who identify as transgender or transsexual, and often results in gender dysphoria. The causes of gender incongruence have been studied for decades.

Masculinizing hormone therapy, also known as transmasculine hormone therapy or female-to-male hormone therapy, is a form of hormone therapy and gender affirming therapy which is used to change the secondary sexual characteristics of transgender people from feminine or androgynous to masculine. It is a common type of transgender hormone therapy, and is predominantly used to treat transgender men and other transmasculine individuals who were assigned female at birth. Some intersex people also receive this form of therapy, either starting in childhood to confirm the assigned sex or later if the assignment proves to be incorrect.

Feminizing hormone therapy, also known as transfeminine hormone therapy, is hormone therapy and sex reassignment therapy to change the secondary sex characteristics of transgender people from masculine or androgynous to feminine. It is a common type of transgender hormone therapy and is used to treat transgender women and non-binary transfeminine individuals. Some, in particular intersex people, but also some non-transgender people, take this form of therapy according to their personal needs and preferences.

<span class="mw-page-title-main">Transsexual</span> People experiencing a gender identity inconsistent with their assigned sex

A transsexual person is someone who experiences a gender identity that is inconsistent with their assigned sex, and desires to permanently transition to the sex or gender with which they identify, usually seeking medical assistance to help them align their body with their identified sex or gender.

<span class="mw-page-title-main">Trans woman</span> Woman assigned male at birth

A trans woman is a woman who was assigned male at birth. Trans women have a female gender identity and may experience gender dysphoria. Gender dysphoria may be treated with gender-affirming care.

<span class="mw-page-title-main">Cyproterone acetate</span> Chemical compound

Cyproterone acetate (CPA), sold alone under the brand name Androcur or with ethinylestradiol under the brand names Diane or Diane-35 among others, is an antiandrogen and progestin medication used in the treatment of androgen-dependent conditions such as acne, excessive body hair growth, early puberty, and prostate cancer, as a component of feminizing hormone therapy for transgender individuals, and in birth control pills. It is formulated and used both alone and in combination with an estrogen. CPA is taken by mouth one to three times per day.

Puberty blockers are medicines used to postpone puberty in children. The most commonly used puberty blockers are gonadotropin-releasing hormone (GnRH) agonists, which suppress the natural production of sex hormones, such as androgens and estrogens. Puberty blockers are used to delay the development of unwanted secondary sex characteristics in transgender children, so as to allow transgender youth more time to explore their gender identity. The same drugs are also used to treat other conditions, such as precocious puberty in young children and some hormone-sensitive cancers in adults.

The real-life experience (RLE), sometimes called the real-life test (RLT), is a period of time or process in which transgender individuals live full-time in their identified gender role in order to be eligible to receive gender-affirming treatment. The purpose of the RLE has been to confirm that a given transgender person could function successfully as a member of said gender in society, as well as to confirm that they are sure they want to live as said gender for the rest of their life. A documented RLE was previously a requirement of many physicians before prescribing gender-affirming hormone therapy, and a requirement of most surgeons before performing gender-affirming surgery.

Transgender pregnancy is the gestation of one or more embryos or fetuses by transgender people. As of 2024, the possibility is restricted to those born with female reproductive systems. However, transition-related treatments may impact fertility. Transgender men and nonbinary people who are or wish to become pregnant face social, medical, legal, and psychological concerns. As uterus transplantations are currently experimental, and none have successfully been performed on trans women, they cannot become pregnant.

Transgender health care includes the prevention, diagnosis and treatment of physical and mental health conditions for transgender individuals. A major component of transgender health care is gender-affirming care, the medical aspect of gender transition. Questions implicated in transgender health care include gender variance, sex reassignment therapy, health risks, and access to healthcare for trans people in different countries around the world. Gender affirming health care can include psychological, medical, physical, and social behavioral care. The purpose of gender affirming care is to help a transgender individual conform to their desired gender identity.

The medical uses of bicalutamide, a nonsteroidal antiandrogen (NSAA), include the treatment of androgen-dependent conditions and hormone therapy to block the effects of androgens. Indications for bicalutamide include the treatment of prostate cancer in men, skin and hair conditions such as acne, seborrhea, hirsutism, and pattern hair loss in women, high testosterone levels in women, hormone therapy in transgender women, as a puberty blocker to prevent puberty in transgender girls and to treat early puberty in boys, and the treatment of long-lasting erections in men. It may also have some value in the treatment of paraphilias and hypersexuality in men.

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