A person's sex refers to the characteristics and traits of biological sex (eg, genitals, chromosomes) used to categorize a person as male or female sex. Gender identity is a person’s internal sense of being male, female or something else, which may or may not correspond to an individual's sex assigned at birth or sex characteristics (1). Gender identities include traditional masculinity or femininity, with a growing cultural recognition that some people do not fit into the traditional male-female dichotomy (called the gender binary). These people may refer to themselves as genderqueer, nonbinary, nonconforming, or one of many other terms. Moreover, definitions and categorizations of gender roles may differ across societies.
Many cultures are more tolerant of gender-nonconforming behaviors in young girls (eg, doing activities or wearing clothing that are more typical for boys) than in boys (ie, behaviors that are considered effeminate). As part of normal development, many boys role-play as girls or mothers, including trying on their sister’s or mother’s clothes or engaging in stereotypical behaviors or expressing interests associated with girls in a given society. Gender incongruent behaviors (those that differ from cultural norms for a person's birth sex) in children is generally not considered a disorder and usually does not persist into adulthood or lead to a transgender identity or gender dysphoria.
The term cisgender, which applies to the majority of people, is used to refer to people whose gender identity corresponds to their sex assigned at birth. Sex and gender (both in terms of identities and roles) are not equivalent in people with gender incongruence or gender dysphoria, and are considered clinically as distinct characteristics. (See .)
Nonbinary gender identity refers to individuals who experience their gender as different from the typical western views of binary gender identity (masculine or feminine). Nonbinary describes people with different types of gender identity, including people who do not identify with any gender, those who identify with multiple genders, and those who may experience different genders over time or in different contexts (gender fluid) (2). In English, rather than gendered pronouns (he/him/his or she/her/hers), nonbinary people may use the pronouns they/them/theirs or newly created pronouns such as "ze/zir/hir" or "e/er/ers," among others; gender and pronouns preferred by nonbinary people differ by language and other factors.
For most people, there is congruity between their sex assigned at birth, gender identity, and gender role. Gender incongruence is a marked and persistent incongruence between an individual´s experienced gender and the assigned sex (3). If an individual experiences or displays gender incongruity or gender nonconformity, this itself is not considered a disorder. It is considered a normal variant in human gender identity and expression. However, when the perceived mismatch between birth sex and the internal sense of gender identity causes someone significant distress or functional impairment, a clinical diagnosis of gender dysphoria may be appropriate. Gender dysphoria is a diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), and is divided into 2 sets of diagnostic criteria, one for children and one for adolescents and adults (4).The diagnosis is defined by the person's distress rather than by the presence of gender incongruity or identity.
According to some experts, the diagnosis of gender dysphoria is primarily a general medical condition with attendant psychiatric symptoms, akin to disorders of sex development, and not primarily a psychiatric disorder. As a result, gender incongruence and gender dysphoria are not listed as mental health conditions in the International Classification of Diseases, 11th Revision, but rather in the sexual health chapter (5). The World Health Organization made this change, in part, to reduce stigma for an already stigmatized condition (6, 7). Conversely, others consider even extreme forms of gender incongruity to be neither a medical nor a psychiatric condition, but rather rare normal variants on the spectrum of human gender identity and expression.
The distress of gender dysphoria is typically described as a combination of anxiety, depression, irritability, and the pervasive sense of not feeling comfortable in one's body. People with severe gender dysphoria may experience severe, disturbing, and long-standing symptoms. They usually have a strong wish to change their body medically and/or surgically to make their body more closely align with their gender identity.
Irrespective of the viewpoint about the clinical nature of gender incongruence and dysphoria, there is substantial evidence that transgender persons as a population suffer from an increased burden of medical, mental health, and sexual health diagnoses, often associated with barriers to access to care (8, 9). People with gender incongruence may also have associated comorbidities including substance use disorders, anxiety disorders, depression, suicidality, and autism spectrum disorders, often at higher rates than the cisgender population (10). Gender dysphoria, while extremely common at some point in the lifetime of gender incongruent people, is not universal. Likewise, those who identify as transgender may, or may not, have a current diagnosis of gender dysphoria. When defined symptoms are present and reach a threshold of clinical significance, a diagnosis of gender dysphoria may be warranted.
Epidemiology of Gender Incongruence and Gender Dysphoria
There are insufficient data to determine the precise prevalence of gender incongruence or gender dysphoria and many studies are surveys in which individuals report their gender identity rather than data from medical records regarding those diagnosed with gender dysphoria.
Studies conducted in large health care systems have reported that 0.02 to 0.1% of patients meet Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR) criteria for a diagnosis of gender dysphoria (1). Surveys of individuals in nonclinical settings have reported an even higher proportion of respondents who self-identify as transgender, because many of those individuals who self-identify do not have a diagnosis of gender dysphoria. An analysis of data from United States national surveys from 2017 to 2020 reported that 1.6 million people identified as transgender, including 300,000 adolescents ages 13 to 17 years (1.4% of population in this age range) and 1.3 million adults (0.3%). Of the adults who identified as transgender, 39% (515,200) identified as transwomen, 36% (480,000) identified as transmen, and 26% (341,800) reported they are gender nonconforming (2). While the percentage of adolescents who identify as transgender has increased (3), the percentage and number of adult Americans who identify as transgender has remained relatively unchanged for a decade at 0.5% (2).
Prior to the 2010s, a majority of patients with gender dysphoria who requested treatment had been assigned male at birth (AMAB). Since that time, worldwide there has been a substantial increase in the number of adolescents assigned female at birth (AFAB) who visit clinics for evaluation and treatment (4–6). It is unclear what factors are responsible for this significant change, which has been reported in several countries including the United States, the United Kingdom, and other European countries (7).
A survey by the Williams Institute, a law and public policy research center, reported that approximately 1.2 million adults in the United States identify as nonbinary, including 11% of the lesbian, gay, transgender, and queer or questioning (LGBTQ) population and 43% of people who also identify as transgender (8). In a national survey of gender and gender minority adolescents in the United States, 25 to 50% of gender-diverse people identified as nonbinary (9). Some studies indicate that a majority of nonbinary people were AFAB (10).
Etiology of Gender Incongruence and Gender Dysphoria
The specific etiology of gender incongruence is incompletely understood. Biologic factors (eg, genetics, prenatal hormonal milieu at a critical period in fetal development) are thought to play major roles in determining gender identity. Some studies have found a higher concordance rate for gender dysphoria in monozygotic twins than in dizygotic twins, suggesting a heritable component to gender incongruity (1), whereas others have not found this linkage (2). Some brain imaging studies show functional and anatomic differences in people with gender dysphoria that are consistent with their gender identity rather than their sex assigned at birth (3). Finally, there are genetic studies that demonstrate overrepresentation of certain genes and alleles that, in combination, relate to sex-hormone signaling in transgender people when compared to cisgender controls (4).
Gender dysphoria may be associated with disorders of sex development (DSD; eg, ambiguous genitalia) or a genetic abnormality (eg, Turner syndrome, Klinefelter syndrome). Gender dysphoria generally affects 8.5 to 20% of people with DSD but the rate varies widely depending on the type of DSD, with rates as high as 63% in those with 5-alpha reductase 2 and 17-beta-hydroxysteroid dehydrogenase 3 abnormalities (5). When sex labeling and rearing are confusing (eg, in cases of ambiguous genitals or genetic syndromes altering genital appearance [eg, androgen insensitivity syndromes]), children may become uncertain about their gender identity or role, although the additional contribution of environmental factors remains controversial. However, when sex labeling and rearing are unambiguous, the presence of ambiguous genitals may not affect a child’s gender identity development.
The formation of a secure, unconflicted gender identity and gender role is also influenced by psychosocial and social factors, such as the character of the parents’ emotional bond, relationship each parent has with the child, and social milieu and cultural and subcultural contexts in which a child is reared (6).
Symptoms and Signs of Gender Incongruence and Gender Dysphoria
Although this section is called symptoms and signs of gender incongruence and gender dysphoria, it also discusses experiences and characteristics of gender-diverse individuals who do not have gender dysphoria.
Symptoms in adults
Many adults diagnosed with gender dysphoria have gender dysphoria symptoms in early childhood or experience a sense of being "different," but some do not present until adulthood and had no evidence of childhood gender incongruence. Transwomen may first identify as cross-dressers and only later in life come to embrace their transgender identity.
Some people with gender dysphoria initially make choices consistent with their sex assigned at birth (eg, marriage, military service), and frequently admit, in retrospect, that they were not comfortable with their emerging transgender/gender-diverse feelings and made life decisions to try to avoid dealing with them. For those AMAB, this has been described as a "flight into hypermasculinity" (1, 2). Once they accept their transgender identity and publicly transition gender, many transgender people blend seamlessly into the fabric of society in their preferred gender identity—with or without gender-affirming hormone therapy or gender-affirming surgery.
Transgender people may feel comfortable with a variety of methods of expressing their gender identity. Some patients AMAB are satisfied with achieving a more feminine appearance and obtaining female identification documents (eg, driver’s license, passport) to allow them to work and live in society as women. Likewise, many patients AFAB choose to proceed with a social transition, and with the assistance of gender-affirming testosterone therapy (whether or not mastectomies and/or chest reconfiguration are performed) appear and sound quite masculine. Transgender people may feel comfortable with a variety of methods of expressing their gender identity. Some patients AMAB are satisfied with achieving a more feminine appearance and obtaining female identification documents (eg, driver’s license, passport) to allow them to work and live in society as women. Likewise, many patients AFAB choose to proceed with a social transition, and with the assistance of gender-affirming testosterone therapy (whether or not mastectomies and/or chest reconfiguration are performed) appear and sound quite masculine.
Gender-diverse people experience mental health issues, which may include anxiety, depression, substance use disorders, and suicidal behavior, at levels substantially higher than those of their cisgender peers (3). These issues may be related to societal and family stressors associated with lack of acceptance of gender-nonconforming behaviors and marginalization, often referred to as minority stress. Health disparities in access to mental health and overall health care services are well-documented in people with gender-dysphoria and may be associated with poverty, barriers to access to care, discrimination, and clinician discomfort in providing them with appropriate care.
Symptoms in children
Childhood gender diversity is a frequent occurrence in general human development (4) and is not itself a psychiatric disorder nor necessarily an indication that a child has a transgender identity (5).
Childhood gender dysphoria is a clinical diagnosis that often manifests as early as age 2 to 3 years but may become apparent at any age. Most children with gender dysphoria are not evaluated until they are age 6 to 9. Children with gender dysphoria commonly present with the following for at least a 6-month period (6):
Prefer cross-dressing
Insist that they are of the other sex
Wish that they would wake up as the other sex
Prefer participating in the stereotypical games and activities of the other sex
Prefer playmates of the other gender
Have a strong dislike of their sexual anatomy
For example, a young girl may insist she will grow a penis and become a boy, and she may stand to urinate. A boy may fantasize about being female and avoid rough-and-tumble play and competitive games. He may also wish to be rid of his penis and testes. Children with gender incongruence may experience distress at the physical changes of puberty is present; this is often followed by a request during adolescence for treatment to change their body appearance and other characteristics (eg, voice) to be consistent with their gender identity (gender-affirming treatment).
For gender-incongruent prepubescent children, gender identity in adulthood cannot be reliably predicted in advance. Some studies have found that a majority of study participants with childhood gender incongruence remained stable in this gender identity as adolescents (7). In other studies, among study participants diagnosed with gender dysphoria as children, a minority continued to meet diagnostic criteria for gender dysphoria as adults (8, 9); also a minority of those who expressed levels of gender incongruence that did not meet diagnostic criteria for gender dysphoria continued to express gender incongruity as adults.
There is considerable controversy over whether or at which age to support the social and/or medical gender transition of young prepubertal children with gender dysphoria. There is no conclusive research to guide this decision (10, 11); however long-term, prospective studies are underway (7).
The World Professional Association for Transgender Health (WPATH) Standards of Care, version 8 (12) provide guidance for experts working in this sensitive area. These guidelines recommend that parents/caregivers and health care professionals respond supportively to children who desire to be acknowledged as the gender that matches their internal sense of gender identity. They also recommend that parents/caregivers and health care professionals support children to continue to explore their gender throughout the prepubescent years, regardless of social transition (12).
Gender-diverse children and adolescents as a group are more likely to experience trauma, bullying, isolation, and mental health difficulties than their cisgender peers (13, 14). The well-documented increase in suicidality and depression in adolescents who identify as transgender or gender diverse has been the subject of multiple studies, including a systematic review of 21 studies (15, 16, 17).
Some transgender children or adolescents make a social transition (transition that does not involve any medications or surgery). This may involve one or more of the following changes: personal expression changes (eg, changes in hair styles, clothing, jewelery choices); communication of experienced/affirmed gender to family, friends, and to other people publicly; name change, pronoun change, changing sex documented in school or other records; changing the bathroom and locker room used to be consistent with experienced gender; participation in "other" gender sports, recreational clubs, camps, and other organized activities(5).
Some children and adolescents who express gender incongruence, including those who socially transition, may ultimately decide to return to the gender role associated with their sex assigned at birth. This phenomenon has been referred to as "detransition" or "retransition." A longitudinal study of 317 young adolescents with gender dysphoria reported that 2.5% had retransitioned at an average follow-up of 5 years (18). Detransition is unusual in those who have completed medical and surgical gender transition and is more likely in people AMAB than those AFAB (19).
Diagnosis of Gender Incongruence and Gender Dysphoria
Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR) criteria
International Classification of Diseases (ICD)-11 criteria (not yet used in all countries)
Assessment and diagnosis in all age groups
Assessment of an individual regarding gender incongruence or gender dysphoria often includes:
Clinical interview of the individual (and for children, interviewing parents/caregivers) about asserted gender identity and gender expression, currently and historically
Assessment for evidence of dysphoria, gender incongruence
Review of relevant medical and mental health history (and for children, developmental history)
The presence of significant personal or family stressors or risks should be assessed (eg, substance use, exposure to violence, poverty)
Assessment for other mental health conditions that are often associated with gender dysphoria, including depression, anxiety, substance use disorders, tobacco use, suicidality.
In addition, the individual's family and psychosocial contexts are important, including attitudes, support, and challenges regarding gender diversity in the person and among family, friends, and other important contacts (eg, peers, teachers, coworkers, community members). The presence of significant personal or family stressors or risks should be assessed (eg, substance use, exposure to violence, poverty). The World Professional Association for Transgender Health (WPATH) Standards of Care, version 8 provide a detailed section on the evaluation of gender-diverse patients at all stages of the life cycle (1).
Gender incongruence is defined in the ICD-11 as a marked and persistent incongruence between an individual's experienced gender and the assigned sex (2). Because ICD-11 is used in Europe and some other world regions, but not yet in the United States, gender incongruence does not have a diagnostic code in the United States, and in clinical practice, the term is typically used only in reference to children.
Gender dysphoria is expressed differently in different age groups (1). The diagnosis of gender dysphoria in all age groups, per DSM-5-TR criteria, requires the presence of both of the following (3):
Marked incongruity between birth sex and experienced/expressed gender identity that has been present for ≥ 6 months
Clinically significant distress or functional impairment resulting from this incongruity
Diagnosis of gender dysphoria in adults and adolescents
DSM-5-TR diagnostic criteria for gender dysphoria in adults and adolescents require ≥ 2 of the following (3):
A marked incongruence between one's experienced/expressed gender and primary and/or secondary sex characteristics (or in young adolescents, the anticipated secondary sex characteristics)
A strong desire to be rid of one’s primary and/or secondary sex characteristics because of a marked incongruence with one’s experienced/expressed gender (or in young adolescents, a desire to prevent the development of the anticipated secondary sex characteristics)
A strong desire for the primary and/or secondary sex characteristics of the other gender
A strong desire to be the other gender (or some alternative gender different from one’s assigned gender)
A strong desire to be treated as another gender (or some alternative gender different from one’s assigned gender)
A strong conviction that one has the typical feelings and reactions of the other gender (or some alternative gender different from one’s assigned gender)
The condition must be associated with clinically significant distress or impairment in social, occupational, or other important areas of functioning.
Diagnosis of gender dysphoria in children
DSM-5-TR diagnostic criteria for gender dysphoria in children require ≥ 6 of the following (1 of which must be the first criterion) (3):
A strong desire to be of the other gender or an insistence that one is the other gender (or some alternative gender different from one’s assigned gender)
In boys (assigned gender), a strong preference for cross-dressing or simulating female attire; or in girls (assigned gender), a strong preference for wearing only typical masculine clothing and a strong resistance to the wearing of typical feminine clothing
A strong preference for cross-gender roles in make-believe play or fantasy play
A strong preference for toys, games, and activities stereotypical for the other gender
A strong preference for playmates of the other gender
A strong rejection of toys, games, and activities typical of the gender that matches their birth sex
A strong dislike of one's sexual anatomy
A strong desire for the primary and/or secondary sex characteristics that match one's experienced gender
The condition must be associated with clinically significant distress or impairment in social settings, school, or other important areas of functioning.
Self-identification as a different gender than that assigned at birth must not be merely a desire for perceived cultural advantages of being a different gender. For example, a boy who says he wants to be a girl predominantly because he will receive the same special treatment his younger sister receives is not likely to have a diagnosis of gender dysphoria.
Treatment of Gender Dysphoria
For many adults or adolescents, gender-affirming hormone therapy and sometimes gender-affirming surgeries (breast, genital, or facial surgery)
Sometimes other treatments (eg, voice therapy, electrolysis)
Psychotherapy to address coexisting mental health concerns, transition-related issues, and other problems, but is not mandatory to access medical and/or surgical treatments for gender dysphoria
The goal of treatment for transgender persons, according to the World Professional Association for Transgender Health (WPATH), is to achieve "lasting personal comfort with their gendered selves with the aim of optimizing their overall physical health, psychological well-being, and self-fulfilment" (1).
Gender-nonconforming or gender-incongruent behavior, such as cross-dressing, is not considered a disorder and does not require treatment if it occurs without concurrent gender dysphoria (ie, without clinically significant psychological distress or functional impairment). When treatment is required for gender dysphoria, it is aimed at relieving patients' distress and helping them adapt to rather than trying to dissuade them from their identity. Using psychotherapy to try to "convert" a person's established transgender identity (so-called reparative therapy or conversion therapy) is not only ineffective but can be harmful to patients, is considered unethical, and is illegal in some jurisdictions.
For most persons with gender dysphoria, the primary objective in seeking medical help is not to obtain mental health treatment, but to obtain gender-affirming treatments in the form of hormone therapy and/or gender-affirming surgery (previously known as sex reassignment or gender affirming surgery) to make their physical appearance consistent with their gender identity. When gender dysphoria is appropriately diagnosed and treated, the psychological distress may resolve with a combination of one or more of the main modalities: psychotherapy, social transition, gender-affirming hormone therapy, and/or gender-affirming surgeries (1, 2).
Surgery may help certain patients achieve greater adaptation and life satisfaction. Most experts recommend surgery only for patients who have been assessed by an appropriately trained and experienced clinician and who have been treated according to the current WPATH Standards of Care, which generally includes a course of gender-affirming hormone therapy when indicated. Clinicians often advise patients to live in their preferred gender role for a year before having irreversible genital surgery.
Fertility-preservation techniques, such as embryo, oocyte, or sperm cryopreservation or delaying initiation of gender-affirming hormonal treatments, should be discussed prior to treatment (1, 3 ).
Studies have found that gender-affirming surgery is associated with improved mental health outcomes in people with gender dysphoria (4, 5, 6). Based on these findings, this surgery is considered medically necessary in patients with gender dysphoria who are highly motivated and have been evaluated by appropriate experts and who have met the criteria outlined in the WPATH Standards of Care, version 8 (2). It should be noted that gender-affirming surgeries are not limited to genital interventions but may also include facial changes, vocal cord surgery, breast augmentation, hair removal, tracheal shave (surgery to reduce size of Adam's apple), or other nongenital surgeries.
Many people who have gender-affirming surgery are able to have satisfactory sexual relations. After surgery, the ability to achieve orgasm is often retained, and some people report feeling comfortable sexually for the first time. However, few people endure gender-affirming surgery for the sole purpose of being able to function sexually as the opposite sex. Confirmation of their inner sense of gender identity is usually the motivation.
Mental health professionals can do the following to help patients with gender dysphoria make informed decisions:
Assess and treat comorbid disorders (eg, depression, substance use disorders)
Help patients deal with the negative effects of stigma (eg, disapproval, discrimination)
Help patients find a gender expression that is comfortable
If applicable, facilitate gender role changes, coming out (informing other people about one's transgender identity), and transitioning
Provide a safe place to explore gender identity and the risks and benefits of potential treatments
The decision of an individual to share information about their gender identity with family and the public, independent of desired treatments, is often fraught with potential social problems for patients (7, 8 ). Such issues include the potential loss of family, spouse/partner, friends and the loss of employment or housing due to continued discrimination against gender-diverse persons. In some parts of the world, being publicly gender diverse is also illegal and subjects transgender persons to potential serious legal consequences, including imprisonment or execution.
Participation in gender support groups, available in most large cities or through the internet, is often helpful, especially during the transition process.
Individuals assigned male at birth (AMAB)
For transwomen, gender-affirming medical therapy consists of feminizing hormones in moderate doses (eg, estradiol transdermal patch 0.1 to 0.2 mg/day or oral estradiol 2 to 8 mg/day) with an anti-androgen (eg, spironolactone 100 to 400 mg/day). in moderate doses (eg, estradiol transdermal patch 0.1 to 0.2 mg/day or oral estradiol 2 to 8 mg/day) with an anti-androgen (eg, spironolactone 100 to 400 mg/day).
Feminizing hormones have significant beneficial effects on the symptoms of gender dysphoria, often before there are any visible changes in secondary sexual characteristics (eg, breast growth, decreased facial and body hair growth, redistribution of fat to the hips). Feminizing hormones, even without psychological support or surgery, are enough to make some patients feel sufficiently comfortable as women (9).
Hormone therapy is typically combined with electrolysis, voice therapy, and other feminizing treatments. Feminizing hormones do not eliminate facial or body hair; however, estrogen combined with anti-androgen therapy may substantially slow male pattern baldness progression.
Gender-affirming surgery is requested by an increasing number of transwomen. Although there are several approaches, the most common surgery involves removal of the penis and testes and creation of a neovagina. A part of the glans penis is retained as a clitoris, which is usually sexually sensitive and retains the capacity for arousal and orgasm in a majority of cases.
Some patients also have nongenital, gender-affirming surgical procedures such as breast augmentation, facial feminization surgeries (eg, rhinoplasty, brow lift, hairline changes, jaw reconfiguration, tracheal cartilage shave [reduction of the laryngeal cartilage]), or vocal cord surgeries to change the quality of the voice (10).
Individuals assigned female at birth (AFAB)
For transmen, gender-affirming pharmacologic therapy consists of testosterone therapytestosterone therapy. Testosterone preparations permanently deepen the voice, induce a more masculine muscle and fat distribution, induce permanent clitoromegaly, and promote growth of facial and body hair. Some of these physical changes are permanent, even with discontinuation of treatment. . Testosterone preparations permanently deepen the voice, induce a more masculine muscle and fat distribution, induce permanent clitoromegaly, and promote growth of facial and body hair. Some of these physical changes are permanent, even with discontinuation of treatment.
Testosterone can be administered intramuscularly or topically (patch or gel). Oral testosterone generally has poor bioavailability and is not the recommended route of administration. Testosterone cypionate or enanthate are administered intramuscularly in doses of 20 to 50 mg/week or 40 to 100 mg every 2 weeks, with maintenance (long term) doses of 50 to 100 mg/week or 100 to 200 mg every 2 weeks; alternatively, subcutaneous administration has been reported to be effective for many patients (Testosterone can be administered intramuscularly or topically (patch or gel). Oral testosterone generally has poor bioavailability and is not the recommended route of administration. Testosterone cypionate or enanthate are administered intramuscularly in doses of 20 to 50 mg/week or 40 to 100 mg every 2 weeks, with maintenance (long term) doses of 50 to 100 mg/week or 100 to 200 mg every 2 weeks; alternatively, subcutaneous administration has been reported to be effective for many patients (11). Testosterone patches for gender-affirming treatment typically deliver doses ranging from 2.5 to 10 mg/day, depending on clinical outcomes and laboratory assessments. Some patients report issues with the patches staying in place. Testosterone gels (1%) are typically initiated at 2.5 to 5.0 grams/day, with maintenance doses between 5 to 10 grams/day. Patients using gels must be aware that testosterone can be transferred to others by skin contact for some period of time after administration.). Testosterone patches for gender-affirming treatment typically deliver doses ranging from 2.5 to 10 mg/day, depending on clinical outcomes and laboratory assessments. Some patients report issues with the patches staying in place. Testosterone gels (1%) are typically initiated at 2.5 to 5.0 grams/day, with maintenance doses between 5 to 10 grams/day. Patients using gels must be aware that testosterone can be transferred to others by skin contact for some period of time after administration.
Since the 2010s, there have been increasing rates of gender-affirming surgeries in transmen (12). These individuals often request mastectomy early in treatment, including in late adolescence, because it is difficult to live in the male gender role with a large amount of breast tissue. Breast binding is often practiced by transmen, but this often makes breathing difficult and can cause skin irritation and circulation issues if not done properly (13). Large breasts are difficult to conceal even with binding and are associated with a higher severity of gender dysphoria symptoms.
Hysterectomy and oophorectomy may be performed after a course of masculinizing hormone therapy, including androgenic hormones (eg, testosterone ester preparations 50 to 100 mg intramuscularly or subcutaneously every week or equivalent doses of testosterone creams or gels) if tolerated. , including androgenic hormones (eg, testosterone ester preparations 50 to 100 mg intramuscularly or subcutaneously every week or equivalent doses of testosterone creams or gels) if tolerated.
Some transmen wish to preserve fertility and use their oocytes for a future pregnancy. Fertility issues are important to discuss with patients treated with gender-affirming hormones, as it appears that fertility may be at least temporarily impaired. Patients should be counseled about fertility-preservation options before hormone therapy or surgery (14). Options include cryopreservation of oocytes, ovarian tissue, and embryos. There are insufficient data about long-term effects on fertility of masculinizing hormone therapy. Successful pregnancies after discontinuing testosterone treatments in transmen have been reported. Although fertility is potentially negatively impacted, AFAB patients who do not wish to become pregnant should be counseled that hormone therapy often does not induce sterility and that appropriate contraception should be used (). Options include cryopreservation of oocytes, ovarian tissue, and embryos. There are insufficient data about long-term effects on fertility of masculinizing hormone therapy. Successful pregnancies after discontinuing testosterone treatments in transmen have been reported. Although fertility is potentially negatively impacted, AFAB patients who do not wish to become pregnant should be counseled that hormone therapy often does not induce sterility and that appropriate contraception should be used (15).
Patients may opt for one of the following additional gender-affirming surgeries (16):
An artificial phallus (neophallus) to be created from skin transplanted from the inner forearm, leg, or abdomen (phalloplasty)
A micropenis to be created from fat tissue removed from the mons pubis and placed around the testosterone-hypertrophied clitoris (metoidioplasty)A micropenis to be created from fat tissue removed from the mons pubis and placed around the testosterone-hypertrophied clitoris (metoidioplasty)
With either procedure, scrotoplasty is usually also performed; the labia majora are dissected to form hollow cavities to approximate a scrotum, and testes implants are inserted to fill the neoscrotum.
Anatomic results of neophallus surgical procedures are often less satisfactory in terms of function and appearance than neovaginal procedures for transwomen. This is the possible reason for fewer requests for genital gender-affirming surgery from transmen; however, as techniques for phalloplasty continue to improve, requests for phalloplasty have increased.
Surgical complications are common, especially in procedures that involve extending the urethra into the neophallus. These complications may include urinary tract infection, fistulae, urethral stricture, or a deviated urinary stream.
Nonbinary and other gender-diverse individuals
In health care settings, nonbinary people are less likely to volunteer information about their gender identity than transgender patients; many have had negative experiences with health care professionals who attempt to treat them as though they are on a linear spectrum of gender identity (binary model), which is usually at odds with the patients' self-perception (17).
Some nonbinary people seek gender-affirming medical and/or surgical treatments to alleviate gender dysphoria or incongruence symptoms associated with distress or functional impairment. Treatment goals must be thoroughly understood and the limitations of treatments must be clearly stated. For example, a nonbinary patient assigned male at birth may wish to achieve greater body satisfaction (eg, desired changes in skin, hair growth, fat distribution) through the use of estrogen therapy, but does not wish to develop breasts. These goals may be incompatible with the mechanisms of action of gender-affirming hormonal treatments. Long-term outcome data are lacking regarding medical and surgical treatments in nonbinary populations.
Finally, there are some AMAB individuals who identify as eunuchs and wish to live their lives without the masculine influences of testosterone and without the presence of their penis and/or testicles (18). Many individuals who identify as eunuchs do not describe themselves as transgender and view themselves as having a distinct gender identity as eunuchs. Eunuchs may seek out both medical and surgical interventions to eliminate the masculinizing effects of testosterone, including orchiectomy (1, 19)
Gender dysphoria in children and adolescents
The psychosocial treatment of prepubertal children diagnosed with gender dysphoria remains controversial. Information and guidelines regarding psychosocial treatments, including social transition, are reviewed in the World Professional Association for Transgender Health (WPATH) Standards of Care, version 8 (1). No guidelines or standards endorse or recommend the use of hormonal interventions (puberty blockers or gender-affirming hormones) or gender-affirming surgeries in prepubescent children with a diagnosis of gender incongruence or gender dysphoria, despite some media reports to the contrary (1, 20). Medical care of transgender children and adolescents is often provided in an academic medical center in specialized clinics by a multidisciplinary team. By law, some states in the United States and some other countries limit or ban medical interventions for children or adolescents with a diagnosis of gender dysphoria.
The majority of children who engage in gender-incongruent behaviors do not have a diagnosis of gender dysphoria or incongruence and do not continue into adolescence or adulthood with a transgender identity. Among young children with a diagnosis of gender dysphoria, at this point, it is not possible to reliably predict if these symptoms will continue into adulthood (21, 22).
While there is no clinical consensus on the treatment of prepubertal children with gender dysphoria, it is recognized that attempts to force the child to accept the birth-assigned gender role can be traumatic and unsuccessful (23). Therefore, the predominant treatment modality is psychological support and psychoeducation for children and their parents, using a gender-affirmative model as opposed to a gender-pathologizing model (1). This affirmative approach supports the child in their expressed gender, sometimes including one or more aspects of social transition prior to puberty.
There has been a substantial increase in the number of AFAB adolescents reporting for evaluation and clinical care over the past decade in many western countries, and they now outnumber AMAB adolescents seeking care at most clinics (24).
In early adolescence, puberty-blocking agents have become more commonly used based on research conducted since the 2000s. Medications such as leuprolide (gonadotropin-releasing hormone agonists) prevent the production of In early adolescence, puberty-blocking agents have become more commonly used based on research conducted since the 2000s. Medications such as leuprolide (gonadotropin-releasing hormone agonists) prevent the production oftestosterone and estrogen, thereby "blocking" the progression of puberty. These medications may be given at Tanner Stage II of development, enabling additional time for evaluation youth with gender dysphoria youth prior to permanent pubertal changes (25). (See Endocrine Society Guidelines, 2017.)
If a youth with gender-dysphoria wishes to continue with full transition to a different gender and is assessed as appropriate for additional transition care, puberty-blocking agents may be discontinued and gender-affirming hormone therapy may be given, enabling the onset of a gender-congruent puberty, albeit one that is delayed compared to most peers. These treatments are offered only after evaluation by clinicians with specialized expertise in the diagnosis and management of gender dysphoria in adolescents; this is usually done with consent from parent(s)/guardians and assent from the adolescents (if they are under the age of legal adulthood in a given jurisdiction). As noted above, fertility-preservation techniques should be discussed prior to the onset of any hormonal or surgical interventions.
Key Points
Transgender is a term that refers to people with gender identities that differ from the sex they were assigned at birth; some individuals identify as nonbinary, a category of gender identity that is experienced as outside the concept of the masculine-feminine binary.
Only a minority of people who identify as transgender, gender diverse, or nonbinary meet criteria for a diagnosis of gender dysphoria.
Diagnose gender dysphoria only when distress and/or functional impairment associated with gender incongruency are significant and persist ≥ 6 months.
When treatment is required, it is aimed at relieving patients' distress and helping them adapt to rather than trying to dissuade them from their gender identity.
The treatment of prepubertal children diagnosed with gender dysphoria does not include the use of hormonal medications or surgeries.
