Hormone Replacement Therapy (trans)
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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 hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effect ...
s and other
hormonal medication A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required f ...
s are administered to
transgender A transgender (often abbreviated as trans) person is someone whose gender identity or gender expression does not correspond with their sex assigned at birth. Many transgender people experience dysphoria, which they seek to alleviate through ...
or
gender nonconforming Gender variance or gender nonconformity is behavior or gender expression by an individual that does not match masculine or feminine gender norms. A gender-nonconforming person may be variant in their gender identity, being transgender or non-bina ...
individuals for the purpose of more closely aligning their
secondary sexual characteristic Secondary sex characteristics are features that appear during puberty in humans, and at sexual maturity in other animals. These characteristics are particularly evident in the sexually dimorphic phenotypic traits that distinguish the sexes of a s ...
s with their
gender identity Gender identity is the personal sense of one's own gender. Gender identity can correlate with a person's assigned sex or can differ from it. In most individuals, the various biological determinants of sex are congruent, and consistent with the ...
. This form of hormone therapy is given as one of two types, based on whether the goal of treatment is
masculinization Virilization or masculinization is the biological development of adult male characteristics in young males or females. Most of the changes of virilization are produced by androgens. Virilization is most commonly used in three medical and biology ...
or
feminization Feminization most commonly refers to: * Feminization (biology), the hormonally induced development of female sexual characteristics * Feminization (activity), a sexual or lifestyle practice where a person assumes a female role * Feminization (soci ...
: *
Masculinizing hormone therapy Masculinizing hormone therapy, also known as transmasculine hormone therapy, or female-to-male (or FTM) hormone therapy, is a form of hormone therapy and gender affirming therapy which is used to change the secondary sexual characteristics of t ...
– for
transgender men A trans man is a man who was assigned female at birth. The label of transgender man is not always interchangeable with that of transsexual man, although the two labels are often used in this way. ''Transgender'' is an umbrella term that incl ...
or
transmasculine A transgender (often abbreviated as trans) person is someone whose gender identity or gender expression does not correspond with their sex assigned at birth. Many transgender people experience dysphoria, which they seek to alleviate through tr ...
people; consists of
androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...
s and
antiestrogen Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor (ER) and/or ...
s. *
Feminizing hormone therapy 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 co ...
– for
transgender women A trans woman or a transgender woman is a woman who was assigned male at birth. Trans women have a female gender identity, may experience gender dysphoria, and may transition; this process commonly includes hormone replacement therapy and ...
or
transfeminine A transgender (often abbreviated as trans) person is someone whose gender identity or gender expression does not correspond with their sex assigned at birth. Many transgender people experience dysphoria, which they seek to alleviate through ...
people; consists of
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...
s and
antiandrogen Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the ...
s. Some
intersex Intersex people are individuals born with any of several sex characteristics including chromosome patterns, gonads, or genitals that, according to the Office of the United Nations High Commissioner for Human Rights, "do not fit typical bin ...
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 Sex is the trait that determines whether a sexually reproducing animal or plant produces male or female gametes. Male plants and animals produce smaller mobile gametes (spermatozoa, sperm, pollen), while females produce larger ones ( ova, of ...
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.


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.UCSF Transgender Care, Department of Family and Community Medicine, University of California San Francisco. Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People; 2nd edition. Deutsch MB, ed. June 2016. Available at transcare.ucsf.edu/guidelines. 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.Deutsch MB, Feldman JL. Updated recommendations from the world professional association for transgender health standards of care. Am Fam Physician. 2013 Jan 15;87(2):89-93.


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. It is important to note that not all
gender nonconforming Gender variance or gender nonconformity is behavior or gender expression by an individual that does not match masculine or feminine gender norms. A gender-nonconforming person may be variant in their gender identity, being transgender or non-bina ...
individuals experience gender dysphoria.


Treatment options


Guidelines

The
World Professional Association for Transgender Health 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 ...
(WPATH) and the Endocrine Society formulated guidelines that created a foundation for health care providers to care for transgender patients.
UCSF The University of California, San Francisco (UCSF) is a public land-grant research university in San Francisco, California. It is part of the University of California system and is dedicated entirely to health science and life science. It con ...
guidelines are also used. There is no generally agreed-upon set of guidelines, however.


Delaying puberty in adolescents

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 The Tanner scale (also known as the Tanner stages or Sexual Maturity Rating (SMR)) is a scale of physical development in children, adolescents and adults. The scale defines physical measurements of development based on external primary and secon ...
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 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 co ...
is typically used by transgender women, who desire the development of feminine
secondary sex characteristic Secondary sex characteristics are features that appear during puberty in humans, and at sexual maturity in other animals. These characteristics are particularly evident in the sexually dimorphic phenotypic traits that distinguish the sexes of a s ...
s. 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 Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...
production Production may refer to: Economics and business * Production (economics) * Production, the act of manufacturing goods * Production, in the outline of industrial organization, the act of making products (goods and services) * Production as a stati ...
and induce
feminization Feminization most commonly refers to: * Feminization (biology), the hormonally induced development of female sexual characteristics * Feminization (activity), a sexual or lifestyle practice where a person assumes a female role * Feminization (soci ...
. Types of medications include
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...
s,
antiandrogen Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the ...
s (testosterone blockers), and progestogens. Most commonly, an estrogen is combined with an antiandrogen to suppress and block testosterone. This allows for
demasculinization Virilization or masculinization is the biological development of adult male characteristics in young males or females. Most of the changes of virilization are produced by androgens. Virilization is most commonly used in three medical and biology ...
and promotion of feminization and
breast development Breast development, also known as mammogenesis, is a complex biological process in primates that takes place throughout a female's life. It occurs across several phases, including prenatal development, puberty, and pregnancy. At menopause, bre ...
. 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 characteristic Secondary sex characteristics are features that appear during puberty in humans, and at sexual maturity in other animals. These characteristics are particularly evident in the sexually dimorphic phenotypic traits that distinguish the sexes of a s ...
s. 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:


Masculinizing hormone therapy

Masculinizing hormone therapy Masculinizing hormone therapy, also known as transmasculine hormone therapy, or female-to-male (or FTM) hormone therapy, is a form of hormone therapy and gender affirming therapy which is used to change the secondary sexual characteristics of t ...
is typically used by transgender men, who desire the development of masculine secondary sex characteristics. Masculinizing hormone therapy usually includes
testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...
to produce
masculinization Virilization or masculinization is the biological development of adult male characteristics in young males or females. Most of the changes of virilization are produced by androgens. Virilization is most commonly used in three medical and biology ...
and suppress the production of
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...
. Treatment options include
oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or or ...
,
parenteral A route of administration in pharmacology and toxicology is the way by which a drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance is applied. ...
, subcutaneous implant, and
transdermal Transdermal is a route of administration wherein active ingredients are delivered across the skin for systemic distribution. Examples include transdermal patches used for medicine delivery. The drug is administered in the form of a patch or ointme ...
( patches,
gel A gel is a semi-solid that can have properties ranging from soft and weak to hard and tough. Gels are defined as a substantially dilute cross-linked system, which exhibits no flow when in the steady-state, although the liquid phase may still dif ...
s). Dosing is patient-specific and is discussed with the physician. The most commonly prescribed methods are
intramuscular Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...
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 characteristic Secondary sex characteristics are features that appear during puberty in humans, and at sexual maturity in other animals. These characteristics are particularly evident in the sexually dimorphic phenotypic traits that distinguish the sexes of a s ...
s. These desired effects include: increased muscle mass, development of facial hair, voice deepening, increase and thickening of body hair, and more.


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 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 co ...
page.


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 Masculinizing hormone therapy, also known as transmasculine hormone therapy, or female-to-male (or FTM) hormone therapy, is a form of hormone therapy and gender affirming therapy which is used to change the secondary sexual characteristics of t ...
page.


Fertility consideration

Transgender hormone therapy may limit fertility potential. Should a transgender individual choose to undergo
sex reassignment surgery Gender-affirming surgery (GAS) is a surgical procedure, or series of procedures, that alters a transgender or transsexual person's physical appearance and sexual characteristics to resemble those associated with their identified gender, and a ...
, their fertility potential is lost completely. Before starting any treatment, individuals may consider fertility issues and
fertility preservation Fertility preservation is the effort to help cancer patients retain their fertility, or ability to procreate. Research into how cancer, ageing and other health conditions effect reproductive health and preservation options are growing. Specifically ...
. Options include
semen cryopreservation Semen cryopreservation (commonly called sperm banking or sperm freezing) is a procedure to preserve sperm cells. Semen can be used successfully indefinitely after cryopreservation. It can be used for sperm donation where the recipient wants the tr ...
,
oocyte cryopreservation Human oocyte cryopreservation (egg freezing) is a procedure to preserve a woman's eggs (oocytes). This technique has been used to enable women to postpone pregnancy to a later date – whether for medical reasons (such as cancer treatment), or fo ...
, and
ovarian tissue cryopreservation Ovarian tissue cryopreservation is cryopreservation of tissue of the ovary of a female. Indications Cryopreservation of ovarian tissue is of interest to women who want fertility preservation beyond the natural limit, or whose reproductive potential ...
. A study presented at ENDO 2019 (the Endocrine Society's conference) shows that even after one year of treatment with testosterone, a
transgender A transgender (often abbreviated as trans) person is someone whose gender identity or gender expression does not correspond with their sex assigned at birth. Many transgender people experience dysphoria, which they seek to alleviate through ...
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-10 or the '' Diagnostic and Statistical Manual of Mental Disorders'' (DSM). 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-10 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-10 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.


ICD-10

The ICD-10 system requires that patients have a diagnosis of either
transsexual Transsexual people experience a gender identity that is inconsistent with their assigned sex, and desire to permanently transition to the sex or gender with which they identify, usually seeking medical assistance (including sex reassignmen ...
ism or gender identity disorder of childhood. The criteria for transsexualism include: * A desire to live and be accepted as a member of the opposite sex, usually accompanied by a sense of discomfort with, or inappropriateness of, one's anatomic sex * A wish to have surgery and hormonal treatment to make one's body as congruent as possible with one's preferred sex Individuals cannot be diagnosed with transsexualism if their symptoms are believed to be a result of another
mental disorder A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitt ...
, or of a genetic or
chromosomal abnormality A chromosomal abnormality, chromosomal anomaly, chromosomal aberration, chromosomal mutation, or chromosomal disorder, is a missing, extra, or irregular portion of chromosomal DNA. These can occur in the form of numerical abnormalities, where ther ...
. For a child to be diagnosed with gender identity disorder of childhood under ICD-10 criteria, they must be pre-pubescent and have intense and persistent distress about being the opposite sex. The distress must be present for at least six months. The child must either: * Have a preoccupation with stereotypical activities of the opposite sex – as shown by cross-dressing, simulating attire of the opposite sex, or an intense desire to join in the games and pastimes of the opposite sex – and reject stereotypical games and pastimes of the same sex, or * Have persistent denial relating to their anatomy. This can be shown through a belief that they will grow up to be the opposite sex, that their genitals are disgusting or will disappear, or that it would be better not to have their genitals.


DSM

The
DSM-5 The ''Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition'' (DSM-5), is the 2013 update to the '' Diagnostic and Statistical Manual of Mental Disorders'', the taxonomic and diagnostic tool published by the American Psychiatri ...
states that at least two of the following criteria must be experienced for at least six months' duration for a diagnosis of gender dysphoria: * A strong desire to be of a gender other than one's assigned gender * A strong desire to be treated as a gender other than one's assigned gender * A significant incongruence between one's experienced or expressed gender and one's
sexual characteristics Sexual characteristics are physical traits of an organism (typically of a sexually dimorphic organism) which are indicative of its biological sex. These can include sex organs used for reproduction and secondary sex characteristics which distingu ...
* A strong desire for the sexual characteristics of a gender other than one's assigned gender * A strong desire to be rid of one's sexual characteristics due to incongruence with one's experienced or expressed gender * A strong conviction that one has the typical reactions and feelings of a gender other than one's assigned gender In addition, the condition must be associated with clinically significant distress or impairment.


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 An out-of-pocket expense (or out-of-pocket cost, OOP) is the direct payment of money that may or may not be later reimbursed from a third-party source. For example, when operating a vehicle, gasoline, parking fees and tolls are considered out-of ...
, 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 The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the European mainland, continental mainland. It comprises England, Scotlan ...
's
National Health Service The National Health Service (NHS) is the umbrella term for the publicly funded healthcare systems of the United Kingdom (UK). Since 1948, they have been funded out of general taxation. There are three systems which are referred to using the " ...
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 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 Gender-affirming surgery (GAS) is a surgical procedure, or series of procedures, that alters a transgender or transsexual person's physical appearance and sexual characteristics to resemble those associated with their identified gender, and a ...
*
Real-life experience (transgender) 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 treat ...


References

{{Gonadotropins and GnRH Endocrine procedures Gender transitioning and medicine