#91923: Clinical Care of the Transgender Patient

It is likely that most healthcare providers will encounter transgender individuals in the course of their professional careers, and all healthcare agencies and providers should be prepared to provide competent and compassionate care for gender-variant individuals. A professional level of knowledge combined with sensitive and empathetic care can help reduce needless stress for these patients. By becoming familiar with current research and striving to understand transgendered patients, healthcare providers can become effective advocates for individuals for whom accessing health care creates considerable anxiety.

One of the objectives of Healthy People 2030 is to "improve the health, safety, and well-being of lesbian, gay, bisexual, and transgender people"[1]. Public Health Infrastructure objective LGBT-01 aims to "increase the number of national surveys that collect data on lesbian, gay, and bisexual populations" [1].

There are a variety of terms used in the transgender community that may not be widely recognized by healthcare providers. In some cases, the words used may be inadvertently offensive or exclusionary, and it is incumbent on all healthcare professionals to have a basic knowledge of the terminology involved in the care of transgender patients. The following definitions are meant to provide an introduction to the preferred terms and possible missteps that may occur when discussing gender and/or sex with patients.

Asexual: An individual who does not experience sexual attraction. There is considerable diversity in individuals' desire (or lack thereof) for romantic or other relationships.

Bottom surgery: Popular terminology for genital surgery, particularly among female-to-male transpersons. Also called "lower surgery."

Cisgender: People whose gender identity and gender expression align with their biological sex. This is a newer term used within the transgender community to refer to those who are not transgender.

Coming out: The process of accepting and telling others about one's heretofore hidden gender identity or sexual orientation.

Crossdresser: A person who wears the clothing, jewelry, and/or makeup not traditionally associated with their anatomical sex. Crossdressers have no desire to change their anatomical sex. This is a preferred term to "transvestite," which is considered pejorative in the transgender community.

Female-to-male (FTM): A person assigned as female at birth but who identifies and lives as or hopes to live as a man. Synonymous with "transgender man" or "transman."

Gender: Social categories that are differentiated by psychosocial characteristics and role expectations. In our society, gender is initially assigned based on biological sex.

Gender dysphoria: The distress and suffering experienced when gender identity and biologic sex are not completely congruent. This term is used in the fifth revised edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) and is considered less stigmatizing than "gender identity disorder."

Gender expression: The external manifestation of a person's gender identity, which may or may not conform to the socially defined behaviors and external characteristics that are commonly referred to as either masculine or feminine. This is generally expressed through carriage, dress, grooming, hairstyles, jewelry, mannerisms, physical characteristics, social interactions, and speech patterns.

Gender fluid: A wider and ever-changing form of gender expression in which the experienced or expressed gender varies from day to day.

Gender identity: An individual's internal sense of gender, or sense of being a man, woman, both, or neither. Gender identity may not be binary, and some now consider it to be a spectrum. A person's gender identity may or may not match their biological sex.

Gender identity disorder (GID): A DSM-IV-TR diagnosis given when strong and persistent cross-gender identification, combined with a persistent discomfort with one's sex or sense of inappropriateness in the gender role of that sex, causes clinically significant distress. This term has been replaced in the DSM-5-TR with "gender dysphoria."

Gender non-conforming ("genderqueer"): Individuals whose gender expression is different from society expectations and/or stereotypes related to gender.

Intersex: Anomalies of the sex chromosomes, gonads, reproductive ducts, and/or genitalia. Generally, this includes individuals born with both male and female genitalia or genitalia that are not clearly male or female. This condition is sometimes not identified until puberty.

LGBTQIA: An acronym used to refer to the lesbian, gay, bisexual, transgender/transsexual, queer/questioning, intersex/intergender, asexual/ally community. In some cases, the acronym may be shortened for ease of use or lengthened for inclusivity. Members of this group may also be referred to as gender and sexual minorities and allies (GSMA).

Male-to-female (MTF): A person assigned as male at birth but who identifies and lives as or hopes to live as a woman. Synonymous with "transgender woman" or "transwoman."

Sex: The attributes that characterize biological maleness or femaleness; the best known attributes include the sex-determining genes, the sex chromosomes, the H-Y antigen, the gonads, sex hormones, internal and external genitalia, and secondary sex characteristics.

Sexual orientation: A person's relative responsiveness to sexual stimuli, particularly the sex of the person to whom one is attracted sexually.

Stealth: When a transgender person who has transitioned into a different sex or gender does not divulge the fact of transition.

Transgender: Generally, an umbrella term for those whose gender identity or expression is different than that typically associated with their assigned sex at birth, including transsexual individuals, androgynous people, crossdressers, genderqueers, and other gender non-conforming people who identify as transgender. Some, but not all, of these individuals desire to transition; some, but not all, desire medical changes to their bodies as part of this process. Sometimes abbreviated as trans or trans*.

Transgender man (transman): A transgender individual who, assigned female at birth, currently identifies as a man. In this course, the terms transgender man, female-to-male transgender person, and FTM are used interchangeably. It is important to note that these patients are men and do not require additional description unless medically necessary.

Transgender woman (transwoman): A transgender individual who, assigned male at birth, currently identifies as a woman. In this course, the terms transgender woman, male-to-female transgender person, and MTF are used interchangeably. It is important to note that these patients are women and do not require additional description unless medically necessary.

Transition: The period of time during which transgender persons change their physical, social, and legal characteristics to the gender opposite that of their biologic sex. Transition may also be regarded as an ongoing process of physical change and psychological adaptation. This may involve changing one's identity on legal documents and coming out to family, friends, coworkers, and others.

Transphobia: Dislike of or discomfort with people whose gender identity and/or gender expression do not conform to traditional or stereotypic gender roles.

Transsexual person: Individual whose gender identity is different from their assigned sex at birth and who live in a gender different from their birth sex, or desire to do so. Often, but not always, transsexual people alter or wish to alter their bodies through hormones or surgery in order to align themselves physically with their gender identity. This term first appeared in the DSM-III in 1980 [2].

Transvestite: One who dresses in the clothing of the opposite sex. This is the older clinical name for crossdresser and is considered pejorative and outdated; the preferred term is crossdresser. This term was first included in the DSM-II [2].

While gender variance has been recorded since ancient history, the first scientist to examine gender nonconformity was an Austro-German psychiatrist, Richard von Krafft-Ebing, in the late 1800s [3]. His principle work was Psychopathia Sexualis, published in 1886. In the early twentieth century, Magnus Hirschfeld, a German physician and sexologist, started to explore medical transitions for transgender individuals. He had worked with Lili Elbe, widely regarded as the first person to undergo gender-affirming surgery in 1931 [3]. Unfortunately, most of Hirschfeld's research was destroyed by the Nazis in 1933.

The clinical support of medically transitioning people began in the United States with Harry Benjamin, who used the term "transsexual" to describe people who physically change their body to be congruent with their gender identity [4]. In 1948, he prescribed estrogens in order to bring about physical changes in his first patient, a woman whom he ultimately helped to travel to Germany for gender-confirmation surgery (GCS). He wrote about the provision of care for transsexual individuals in his book The Transsexual Phenomenon, documenting some of what he learned in his long practice treating transsexual men and women in New York City [4,5].

In the 1950s, some GCS was done discretely in the United States, but there were legal objections to castrating otherwise "healthy" men, under the "mayhem" laws. Dr. Elmer Belt, a California urologist, is widely recognized as the first American surgeon to do GCS on a regular basis, and he circumvented the law by moving the testicles into the abdomen rather than removing them [3]. In 1952, Christine Jorgenson made headlines when she became the first American to publicly acknowledge traveling to Denmark for GCS. The news of her conversion brought about a flood of transgender individuals seeking care. While GCS had been performed as early as the 1930s, Dr. Georges Burou (1910–1987) is considered the pioneer of modern techniques. Burou first performed his one-stage GCS technique in 1956 in Casablanca, and by 1973, he had performed more than 3,000 MTF operations. While some FTM surgeries had been performed in Germany in the 1930s and 1940s, the details are lost, and Michael Dillon, an Englishman, is considered to be the first modern FTM individual to undergo surgery. He transitioned in England in the early 1940s and underwent surgery by the pioneering English plastic surgeon, Sir Harold Gillies [3].

In the United States during the 1960s and 1970s, gender identity centers were established at academic medical centers, notably Johns Hopkins, Stanford University, and the University of Minnesota. Although many in the public considered this controversial, the involvement of these prestigious medical institutions helped to "legitimize" the care and diagnosis of transgender individuals. This care was largely covered by health insurance policies and incorporated psychological counseling, endocrine care, and GCS. Despite good outcomes, in 1975 Paul McHugh, chairman of the Department of Psychiatry at Johns Hopkins, advocated against providing care to transgender patients. He asked Johns Hopkins psychiatrist Jon Meyer for follow-up data on patients who received GCS in order to determine how much the surgery had helped them. Meyer found that most of the patients were content with what they had done and only a few regretted it. Despite this, McHugh stated, "But in every other respect, they were little changed in their psychological condition. They had much the same problems with relationships, work, and emotions as before. With these facts in hand I concluded that Hopkins was fundamentally cooperating with a mental illness. We psychiatrists, I thought, would do better to concentrate on trying to fix their minds and not their genitalia" [6]. Shortly thereafter, Johns Hopkins closed their clinic. Other clinic closings followed, with the exception of the University of Minnesota [5]. In the 1970s, the psychological literature on transgender issues was limited and generally pathologized transsexual persons [7].

While academic center-based gender identity clinics were closing, private physicians began providing these services. Dr. Stanley Biber in Trinidad, Colorado, performed his first GCS surgery in 1969. By the time of his retirement in 2003, he had performed more than 5,000 procedures and had made Trinidad the "sex change capital of the world" [8]. During this time, physicians providing GCS could be found in most major cities in the United States. The Erickson Educational Foundation served as a clearinghouse of information and referrals for those seeking treatment.

In 1979, the first standards of care for transgender patients were published by the Harry Benjamin International Gender Dysphoria Association, now known as the World Professional Association of Transgender Health (WPATH). Its aim was to exclude other pathologic states in the differential diagnosis and to confirm the diagnosis. In 1980, transsexualism was included in the third edition of the DSM (DSM-III). While this diagnosis is now under contention in the transgender community because of the stigma of mental disorder, at the time it legitimized the diagnosis [5].

According to the World Health Organization's International Classification of Diseases (ICD-11), the relevant diagnoses fall under Chapter 17, Conditions Related to Sexual Health. Gender Incongruence includes the subcategories of gender incongruence in adolescence/adulthood or childhood. This represents a significant departure from the ICD-10, which categorized "gender identity disorders" under the general category of Mental and Behavioral Disorders [9].

The DSM-IV abandoned the term "transsexualism" and instead used the term "gender identity disorder" [10]. The DSM-5 now uses the term "gender dysphoria." This is defined as "the distress that may accompany the incongruence between one's experienced or expressed gender and one's assigned gender" [11]. The critical element of this diagnosis is the presence of clinically significant distress associated with the condition, as the American Psychiatric Association (APA) points out that gender nonconformity is not a mental disorder. The intent of this change was to better characterize the experiences of affected children, adolescents, and adults and to avoid stigma and ensure clinical care for individuals who see and feel themselves to be a different gender than their assigned gender [11].

Beginning in the mid-1980s, a paradigm shift occurred in looking at gender identity as non-binary. The term "transgender" began being used in the LGBT community as an umbrella term that encompassed crossdressers, transsexual persons, and those individuals who live in the opposite gender role without GCS. Gradually, more and more transgender individuals began to define their gender identity "outside of the boundaries of male versus female, man versus woman, and masculine versus feminine" [12]. According to Fraser, a cultural shift is occurring regarding transgender people, from a pathologic view to an acknowledgement of gender diversity and fluidity [7].

In the 1990s and 2000s, many transgender individuals became experts in medicine, health care, law, and social change. The human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) epidemic generated public health research that revealed the impact of the disease on the transgender community. There has been growth in the online transgender community, which can offer relief from the loneliness and isolation many transgender people face [7].

Because GCS can cost in the range of $30,000 in the United States and is not generally covered by health insurance, many transgender individuals have gone abroad for surgery. Thailand has now replaced Trinidad, Colorado, as the "sex change capital of the world," and the same procedure offered by experienced surgeons in Thailand will cost in the range of $7,000 [13]. The affordable cost paired with Thailand's prominent transgender community led many transgender individuals to consider medical tourism. This trend may be reversed as a result of the Affordable Care Act (ACA) and its regulations, which remove discrimination against transgender status as a pre-existing condition [14].

The critical point for transgender individuals is that there is incongruence between their gender identity and their birth sex. The intensity of this incongruence can vary, and transgender individuals may choose varying degrees of transition. Transgender individuals often attempt to conform to the social gender expectations of their birth sex. For instance, some MTF individuals marry, raise families, and generally lead lives of conformity to the expectations of the male role. FTM persons may conceal their gender identity by leading their lives as lesbians, making gender variance among FTMs "relatively invisible" in society [15].

Transgender individuals experience significant challenges whether or not they choose to disclose their transgender identity. Individuals who "come out" as transgender risk becoming victims of violence, losing relationships, or losing employment. Other challenges include anxiety and depression related to transition issues. These individuals must make decisions regarding how to transition in the workplace and how to assimilate socially appropriate behavior in the new gender. Once disclosure occurs, transgender individuals may face feelings of guilt associated with the disruption of current personal relationships and other relational challenges. Despite these potential negative consequences, the potential positive effects of living authentically in their chosen gender motivate many transgender persons to disclose and begin transition. On the other hand, given these same possibilities, some transgender persons remain closeted and at risk for psychosocial consequences, including depression, anger, anxiety, and suicidal ideation. In fact, caring for patients who present with conditions such as sexual disorders, depression, anxiety, substance abuse, and personality disorders on occasion uncovers transgenderism [16].

At present, scientific investigation has neither established the true incidence nor clarified the etiology of non-conforming gender identity formation [17]. Genetic, physiologic, and psychological causes have been investigated, and available evidence seems to support physiologic causes. Gender dysphoria is not explained by variations in chromosomal patterns or identifiable hormonal abnormalities, nor is there convincing evidence that psychological factors (e.g., being exposed to certain family dynamics or being raised as a member of the opposite sex) cause this condition [18].

Research has focused on neuroscience and how exposure to sex hormones in utero may influence the development of gender dysphoria. In the human brain, there are known sex differences in the central region of the bed nucleus of the stria terminalis. This structure is androgen-dependent and is larger in males than in females. However, the size of the structure in MTF individuals has been found to be within the range of that observed in biological females [19]. This variance is not attributable to chronic estrogen use, as non-transgender men who have received long-term estrogen therapy to control prostate cancer do not show this change [20]. Unfortunately, analysis of the stria terminalis has only been done on postmortem examination, as the structure is too small to visualize with presently available imaging techniques [21].

In a postmortem study of the brains of six MTF individuals, matched with 36 controls from non-MTF individuals, the brains of cisgender men had significantly more somatostatin neurons in the bed nucleus of the stria terminalis than the brains of cisgender women, and the number of these neurons in the brains of MTF participants was statistically similar to that of cisgender women [22]. The sample also included one brain of an FTM individual, for whom the number of somatostatin neurons was in the male range. The researchers hypothesize that this is the result of androgen exposure in early brain development in utero. Presumably, a lack of exposure to androgens in a male fetus at this critical time of development would cause MTF transsexualism, and conversely, exposure to androgens in a female fetus would result in FTM status.

Nawata et al. used computerized tomography to examine cerebral blood flow in 11 FTM individuals and nine non-transsexual female control subjects [23]. They found that in FTM individuals, there was a significant decrease in regional cerebral blood flow in the left anterior cingulate cortex and a significant increase in regional cerebral blood flow in the right insula compared with the control group. The authors hypothesize that regional cerebral blood flow changes in the anterior cingulated cortex and the insula affect neuron networks active in human sexual behavior and consciousness and may contribute to a biological basis of gender dysphoria.

In utero, the formation of both digits and genitals are controlled by the same genes: homeobox or HOX genes. Because testosterone (or the lack thereof) influences the development of genitalia, it has been proposed that this might also hold true for the fingers. In humans, the second digit to fourth digit (2D:4D) ratio differs between the sexes; in girls and women, the two fingers are approximately the same length, but in boys and men, the fourth digit is usually longer than the second [24]. Some have hypothesized that differences in prenatal testosterone levels may cause gender dysphoria, which could be reflected in a difference in finger length ratios. Specifically, lower prenatal testosterone levels would result in MTF individuals, reflected in a female-type 2D:4D ratio. Conversely, higher prenatal testosterone levels would result in FTM individuals, reflected by a male-type 2D:4D ratio.

Kraemer et al. found contradictory results for FTM individuals, whose ratios were significantly more feminized than the female controls [25]. These researchers also found that MTF individuals had ratios that were significantly different from the male control subjects. These findings may indicate that lowered prenatal testosterone levels play a role in gender dysphoria in both sexes. Similar findings by Schneider et al. for MTF individuals support this hypothesis, but these researchers did not find a difference between FTM individuals and female controls [26]. This research indicates a possible biological basis for gender dysphoria, particularly to the role of antenatal androgen exposure, but the exact mechanism is still not understood. A meta-analysis of 2D:4D associations involving 690 individuals found that finger length associations with transgender identity are limited and fluctuate based on sampling variables [27]. Overall, evidence is insufficient to decide whether ratios are sexually asymmetric. Furthermore, several studies have shown that 2D:4D ratio is an inherited trait which varies significantly by ethnicity, leading one study to conclude that there is more difference in 2D:4D ratios between ethnicities than between men and women [175].

Some studies have claimed possible genetic loci related to FTM identity, including the 17-a-hydroxylase (CYP17) genes, the RYR3 gene, and the ERb genes. In addition to the bed nucleus of the stria terminalis, another neuroanatomic region, the interstitial nucleus of the anterior hypothalamus 3 (INAH3) is another area of the brain where some report a difference between men and women. INAH3 is a sexually dimorphic hypothalamic nucleus that is different between males and females and is associated with gender identity and sexual behavior. One report of transgender individuals found that INAH3 volume matched their gender identity [176].

A study of 380 White MTF individuals matched with 344 male subjects examined functional variants in 12 sex hormone-signaling genes. The researchers hypothesized that gender dysphoria in transgender women is associated with genetic variants in sex hormone-signaling genes responsible for undermasculinization and/or feminization of the brain. MTF subjects had genetic variants in ERα, SRD5A2, STS, and SULT2A1 [181]. In Erα, estrogen signaling is reduced. In SULT2A1, fetal sex hormone-binding globulin levels are increased, which may reduce the effects of circulating hormones. SRFD5A2 likely causes a reduction of levels of dihydrotestosterone (DHT). An allele in STS is also associated with attention deficit hyperactivity disorder (ADHD), a condition that has a fivefold increase in individuals with gender dysphoria. These results indicate that gender dysphoria likely has a polygenic basis that involves interactions among various genes and polymorphisms. These interactions may alter the sexual differentiation of the brain in utero. However, while genetics play a role, the study authors emphasize that this is not the sole determinant of gender identity [177].

Another theory of etiology proposes that in some mothers, maternal immunization against the Y-linked minor histocompatibility antigens (H-Y antigens) occurs and increases with each successive male fetus, affecting sexual orientation and gender identity. However, sibling studies have not supported this hypothesis [17].

In summary, the etiology of gender dysphoria is poorly understood. Research has focused on intrauterine hormone exposure, childhood psychological factors, anatomic differences in brain structure and activation, and subtle genetic variations. It is likely that the origin is multifactorial [28,29]. It is also important to note that research into the etiology of transgender identity is not intended to suggest that these patients could or should be "cured."

Because of variability in terminology and definitions, differing modes of presentation, and reluctance to disclose for fear of social stigmatization, it is difficult to obtain accurate data about the prevalence of transgender individuals in the general public [30]. However, as society becomes more accepting and familiar with transgender individuals, more transgender individuals are willing to "come out." The result is that this condition is more prevalent than previously thought.

In the United States in the 1960s, it was estimated that 1 in 100,000 males and 1 in 400,000 females were transgender. By the 1990s, this estimate had increased to 1 in 20,000 males and 1 in 50,000 females [31]. Based on data from 2008, the prevalence of MTF transsexualism was estimated to be 1 in 12,700–45,000 and FTM transsexualism 1 in 30,400–200,000 [32]. Another study cites the incidence of transsexualism at 1 in 20,000 males and 1 in 50,000 females [31]. In the United States, approximately 1.3 million adults and 300,000 teens identify as transgender [33].

By age, transgender identity is expressed by 0.7% of adults 18 to 24 years of age, 0.6% of adults 25 to 69 years of age, and 0.5% of adults 65 years of age or older. This is supported by findings of the 2014–2016 Behavioral Risk Factor Surveillance System (BRFSS), which estimated that 1.5 million Americans identify as transgender—770,000 as MTF and 458,000 as FTM [34]. This translates to an incidence in the general population of 0.35% to 0.53%.

Perhaps the most accurate estimate of the prevalence of transsexualism comes from New Zealand, where since 1995, passport holders have been able to have the sex omitted on their passport. In these cases, sex is shown as "X" on the passport. These persons must provide a statutory declaration stating that they live as a member of the opposite sex. Analysis of passports yields an estimate of MTF transsexualism at 1 in 3,639 and FTM transsexualism at 1 in 22,714. This frequency somewhat matches data from Singapore, which put the MTF prevalence at 1 in 2,900; however, the FTM prevalence in Singapore was 1 in 8,300 [32].

All of these published studies indicate a greater incidence of MTF than FTM transsexualism, with a ratio of anywhere between 2.5:1 and 6:1 [32]. A ratio of 3:1 is common throughout the Western world, but not necessarily elsewhere (e.g., Japan, Serbia). Before puberty, there is a preponderance of MTF individuals, but gender dysphoria in children often resolves, and in adolescents the ratio is closer to 1:1 [29]. The subsequent increase in the MTF to FTM ratio is explained by the higher frequency of men with late-onset gender dysphoria [18].

At present, a precise measure of the incidence and prevalence of transgender individuals remains elusive. There seems to be a slightly higher prevalence of MTF than FTM individuals, although the ratio of MTF to FTM appears to be decreasing. Estimates of prevalence have been increasing over time, which likely reflects increased access to care [28,36].

Caring for transgender individuals is complex and requires some preparation and forethought, taking into account knowledge of anatomical reassignments, the effects of therapy, and cultural sensitivity. This requires an interprofessional collaborative practice that includes an accurate diagnosis, then moving on to psychotherapy or counseling, hormone therapy, the "real-life experience" (i.e., the period of time spent living in the chosen gender prior to GCS), cosmetic interventions (e.g., hair removal), in some cases voice therapy, and surgical interventions [17].

The Institute of Medicine (IOM) has noted that there is a paucity of research on the unique healthcare needs of transgender individuals, and most existing research consists of small nonprobability samples [36]. The IOM calls for an evidence base for providing transgender-specific health care to address gender dysphoria and a more rigorous research program to understand the health implications of hormone use and other transgender-specific issues.

If a primary care provider has little knowledge or training on transgender issues, it is best to disclose this to the patient and seek experts as needed. Jenner points out that competence in taking care of transgender people "…seems to include a healthy portion of unconditional acceptance and an understanding empathy from the healthcare community" [37].

There are often comorbidities among the transgender population. Although research is sparse, it appears that HIV infection rates among MTF transgender individuals are over four times the national average, with even higher rates among transgender people of color [38]. Approximately 42% of MTF transgender persons in the United States are HIV positive [41]. Transgender individuals are also at high risk for other sexually transmitted infections, such as syphilis, gonorrhea, chlamydia, herpes, and human papillomavirus (HPV) [1]. In addition, smoking, drug and alcohol use, depression, and suicide attempts are higher in the transgender population than the general population [39].

Transgender individuals are at risk for HIV as a result of engaging in unprotected sex and from sharing needles used for hormone injections [40,41]. A significant percentage of transgender individuals engage in sex work; 11% of transgender respondents in a large national survey reported engaging in sex work for income, compared with 1% of women in the United States [39]. This survey has been the largest to date of the transgender population, involving 6,450 transgender and gender non-conforming individuals across all 50 states, as well as the District of Columbia, Puerto Rico, Guam, and the U.S. Virgin Islands. The study was conducted on behalf of the National Gay and Lesbian Task Force and the National Center for Transgender Equality.

A staggering 41% of respondents to the survey reported attempting suicide, compared with 1.6% of the general population [39]. The highest rates of suicide attempts in transgender individuals are among those 18 to 44 years of age. Rates are lower among older individuals, with 16% of those older than 65 years of age reporting a suicide attempt, which is inverse to the rates in the general population.

Twenty-six percent of transgender and gender non-conforming individuals have been physically assaulted and 10% have been sexually assaulted [39]. In a study of MTF individuals, 78.1% experienced gender-related psychological abuse and 50% experienced gender-related physical abuse [42]. The Transgender Day of Remembrance is held in November of each year to memorialize those who were killed due to anti-transgender hatred or prejudice. In total, 4,040 murders of trans and gender-diverse individuals have been documented between 2008 and 2021 worldwide [43]. The 2023 update revealed a total of 321 murders in these populations worldwide in 2022–2023 (with 31 of those occurring in the United States), which is slightly less than the 375 reported in 2020–2021 [43]. The National Center for Transgender Equality recommends that ending violence against transgender people should be a public health priority, because of the direct and indirect negative effect violence has on both victims and on the healthcare system that treats them. Transgender individuals also experience a dramatically higher prevalence in intimate partner violence victimization as compared with cisgender individuals. These rates are higher among both MTF and FTM individuals [178].

As noted, transgender individuals have a significantly higher rate of substance abuse than the general population, and there is a correlation between having experienced a transphobic event and substance abuse [44]. Tobacco use is higher in the transgender population, with 30% of transgender or gender non-conforming individuals reporting smoking daily or occasionally, compared with 20.6% in the general population [39].

Reasons for substance abuse in this population include all the reasons others abuse drugs, as well as reasons unique to the transgender community: to suppress the experience of gender dysphoria, to allow desired gender expression, to cope with experiences of transphobia (including internalized transphobia, negative self-image, and trauma), and to cope with involvement in the street economy [45]. Moreover, "safe spaces" where transgender individuals can socialize often include bars, clubs, and restaurants, where smoking and drinking are popular. Tobacco and alcohol companies have also exploited gay and transgender social networks, including gay and transgender magazines, events, and organizations, to aggressively market their products [46]. These kinds of targeted marketing campaigns account, in part, for the higher rates of substance use in the LGBT population.

Barriers to obtaining education because of gender identity issues or harassment lead to higher rates of unemployment, which places transgender people in financial difficulty and makes access to housing and medical care difficult [47]. Schools are not safe places for transgender individuals; 61% report experiencing significant abuse in educational settings [39]. In another study, 90% of transgender youth in schools reported feeling unsafe, compared with 46% of gay or bisexual male students and 41% of lesbian and bisexual female students [48].

Transgender individuals may experience or fear reprisal at work related to their gender identity. Employment was noted as one of the top three immediate perceived needs in the Transgender Needs Assessment Survey [49]. Finding employment is challenging for transgender individuals, especially those who are preoperative and do not have proof of identity in the chosen gender. Transgender people have double the national unemployment rate, and 26% report having lost a job because of their transgender status [50]. A large majority (97%) reports having experienced mistreatment, harassment, or discrimination on the job. In an incidental finding of a study of 376 FTM individuals in the United States, although 48% had a Bachelor's degree or higher, the majority earned less than the U.S. national average [50].

Data from the BRFSS indicate that, compared with cisgender respondents, transgender respondents were younger, more racially/ethnically diverse, had lower educational attainment, tended to have lower income levels, and were more likely to be unemployed, never married, and uninsured [34]. FTM individuals were the most socioeconomically disadvantaged and the least likely to have a college degree, be homeowners, an annual income greater than $50,000, or health insurance. Overall, transgender people experienced a higher burden of mental health problems than cisgender people, likely due to minority stress. There is also a higher likelihood of disability among transgender people, particularly FTM individuals, who have a greater risk for multiple chronic conditions [34].

A 2012 Equal Employment Opportunity Commission ruling included transgender employment discrimination as gender discrimination and consequently protected under Title VII of the Civil Rights Act (Pub. L. 88-352). Some employers now have nondiscrimination policies inclusive of transgender persons, and there has been an improvement in nondiscrimination policies among large corporations. According to the 2024 Human Rights Campaign (HRC) Corporate Equality index (CEI), 97% of Fortune 500 companies and 98% of CEI-rated businesses surveyed offer explicit gender identity non-discrimination protections (significant increases compared to 2015 data) [51]. Additionally, a majority of surveyed CEI-rated businesses (98%) offer education and training programs that specifically include definitions and/or scenarios on gender identity in the workplace. Hundreds of major businesses have adopted gender transition guidelines for employees and their teams to establish best practices in transgender inclusion.

However, there has also been a seeming backlash against the transgender community in the United States. In 2016, North Carolina passed a law that invalidated municipal sexual orientation and gender identity nondiscrimination statutes and pre-emptively banned future nondiscrimination legislation [52]. On a national level, in 2017, the CDC was ordered to avoid use of the term "transgender" and six other words (including "diversity" and "evidence-based") in all budget documents [52].

Strides are also being made in transgender-inclusive healthcare benefits, though these have not kept pace with nondiscrimination protections. Ninety-one percent of the businesses surveyed by the HRC offer transgender-inclusive healthcare coverage, up from just 8% in 2009 [51].

As of 2021, Medicaid provides some transition-related care in 34 states plus the District of Columbia, and in May 2014, Medicare overturned its 30-year ban on coverage for GCS. However, implementation of the policy is proceeding piecemeal by region and may even be legally blocked in some states [53,54]. As of 2024, two states, Mississippi and Arkansas, explicitly allow insurers to refuse providing gender-affirming care [174].

Transgender people face barriers to health care whether seeking preventive medicine, routine and emergency care, or transgender-related services. Transgender people may be poor, uninsured, homeless, or lack access to regular medical care, including providers who are trans-friendly [51]. One survey reported that only 30% to 40% of transgender individuals utilize any regular medical care, due to economic limitations, lack of insurance, comorbidities such as substance abuse, and stigmatization [55]. In addition, some providers will not treat transgender patients because of moral objections [37]. In fact, in 2016, Mississippi and Tennessee passed laws allowing health providers to refuse to provide services if doing so would violate their religious beliefs [52]. The Mississippi bill explicitly identifies same-sex couples and LGBT individuals as being potentially incongruent with some providers' beliefs.

One study showed that 20% of transgender individuals in the United States lack health insurance, and insurance coverage is even worse for racial/ethnic minority transgender individuals [39,56]. Even for those who have insurance, most health insurance plans do not cover the cost of mental health services, cross-sex hormone therapy, or GCS, often because these interventions are deemed cosmetic and non-essential [50]. This barrier exists despite evidence that such treatments are safe and effective and that cross-gender behavior and gender identity issues are not an issue of choice for the individual and cannot be reversed with psychiatric treatment [57].

Before 2014, the Centers for Medicare and Medicaid Services (CMS) did not cover the cost of GCS based on a 1981 evaluation that described the surgery as experimental and cited "the lack of well-controlled, long-term studies of the safety and effectiveness" and "a high rate of serious complications" [58]. However, long-term studies done in Europe have found that GCS is effective, with low complication rates [1]. This policy banning GCS was overturned in May 2014, but because policy guidelines are issued from Medicare contractors by region, widespread implementation has been slow [53]. While the Veterans Administration (VA) has policies in place to provide comprehensive care to transgender veterans, including ongoing hormone therapy, mental health care, and long-term care following GCS, the VA specifically does not cover GCS, on the basis of a VA regulation excluding gender alterations from the medical benefits package [59,60].

Sufficient time has not yet elapsed for the ACA requirement of coverage for transition-related care to apply to grandfathered policies. The ACA bans coverage denial based on being transgender as a pre-existing condition [61]. Although the ACA prohibits discrimination on the basis of sex, including gender identity, in any hospital or health program that receives federal funds and The Joint Commission requires that discrimination on the basis of gender identity is prohibited to maintain accreditation, this information is not widely known and many transgender patients still experience discrimination. The American Medical Association, the APA, the American Congress of Obstetricians and Gynecologists (ACOG), the American Academy of Family Physicians, and the National Association of Social Workers have called for public and private health insurance coverage for this condition [61,62].

Although every major U.S. medical association recognizes that gender-affirming healthcare is medically necessary, several state legislatures have passed bills seeking to limit gender-affirming care for adolescents [174]. As of July 2024, 24 states have passed bills blocking gender-affirming care for adolescents. In three states (Florida, Ohio, and Montana), the bills have been blocked or are on hold, and in an additional nine states, challenges to these bans are pending. As a result, healthcare professions may have confusion regarding the legal care and insurance coverage of these patients.

Lack of health insurance, when combined with provider ignorance about the healthcare needs of transgender people, deters some transgender individuals from seeking and receiving high-quality health care and makes them more likely to obtain hormones illicitly and participate in risky behaviors such as needle sharing and smoking [39,56]. Many transgender individuals have been victims of hostility or discrimination at the hands of healthcare providers [63]. In a large survey of transgender individuals, 19% reported being refused medical care due to their transgender or gender non-conforming status, with even higher numbers among people of color [39]. Even more alarming is the fact that 28% of respondents in this same study reported verbal harassment in medical settings and 2% were physically attacked in medical offices [39]. In 1995, Tyra Hunter, a young, African American, preoperative transgender woman, was injured as a passenger in a car accident. Emergency medical technicians at the scene of the accident uttered derogatory epithets and withdrew medical care after discovering she had male genitalia. After transfer to the emergency department, Hunter received dilatory and inadequate care, resulting in her death. A jury subsequently awarded Hunter's mother $1.75 million in a wrongful death suit [64].

Many transgender individuals fear contact with health professionals. When sick or injured, transgender individuals may postpone medical care due to discrimination or inability to afford it [39]. The difficulty in finding knowledgeable, sympathetic providers has resulted in higher costs, a market for illicit hormone suppliers, and networking systems to identify willing and unwilling providers [37]. A survey of 163 primary care clinicians in the Midwest revealed that 85% of clinicians were willing to provide routine care to transgender patients, but willingness to provide care decreased with the clinician's age. However, the response rate to this survey was 53%, which may have oversampled clinicians more likely to provide care [179]. Additionally, half of respondents were unfamiliar with guidelines centered around gender-diverse and transgender individuals.

The National Center for Transgender Equality recommends that transgender-sensitive care be integrated into the medical profession's standards of care, as part of a commitment to cultural competency. Providers who harass, assault, or discriminate against transgender and gender non-conforming patients should be disciplined.

Transgender individuals in some European countries such as Holland, Sweden, and Belgium are recruited into specialized clinics, given state-funded, evidence-based care, and are followed over time by a consistent team of healthcare professionals. By contrast, most transgender individuals in the United States receive health care in a fragmented, unsystematic fashion and are fortunate if they receive sensitive, non-discriminatory primary care [50]. Because of this fragmented healthcare system, it is difficult to obtain well-controlled studies of transgender care in the United States. Federal agencies, such as the VA, will provide ongoing therapy but will not initiate gender reassignment [37].

Improving access to care can be facilitated, in part, by providing a welcoming environment for transgender patients. The ACOG recommends the adoption and posting of a nondiscrimination policy that signals to both healthcare providers and patients that all persons will be treated with dignity and respect [57]. Also, adding a "transgender" option to checklists on patient visit records can help to better capture information about transgender patients and be a sign of acceptance to that person. Simply asking transgender patients what name and gender they prefer works well [65]. Experts also recommend referring to body parts with gender-neutral language whenever possible, such as "chest" and "genitals," as well as phrases like "persons with vaginas" [65]. Providers should admit their lack of experience with transgender patients and seek guidance from patients regarding their expectations of the visit.

Front office staff can avoid using gender-based pronouns, both on the phone and in person. Instead of asking, "How may I help you, sir?" the staff person could simply ask, "How may I help you?" Avoiding gender-based pronouns when talking to other office staff is also advised. It is acceptable to politely ask a person what name he or she prefers to use. For example, a staff member may say "I would like to be respectful—how would you like to be addressed?" or "What name would you like me/us to use?" After a patient has given a preferred name, it is very important for staff to use this name in all interactions. Not using the patient's preferred name can cause embarrassment and confusion.

In office settings that require insurance or the use of third-party payers, transgender patients may have a name and gender on record that do not match their preferred name and gender. In situations in which a patient's name or gender does not match the insurance or medical records, the staff person could politely ask, "Could your chart be under a different name?" or "What is the name on your insurance?" Offices that utilize electronic health records should have a system to track and record the preferred gender, name, and pronoun of all patients. This can be accomplished by standardizing the notes field to document a preferred name and pronoun for all patients [66]. Some persons who identify as non-binary (i.e., neither or both genders) may prefer that plural pronouns (e.g., they) be used.

Questions should be framed in ways that do not make assumptions about gender identity, sexual orientation, or behavior. Language should be inclusive, allowing the patient to decide when and what to disclose. Assurance of confidentiality should be stressed to the patient to allow for a more open discussion, and confidentiality should be ensured if a patient is being referred to a different healthcare provider. Asking open-ended questions can be helpful during a history and physical. Asking "How can I be a part of affirming your gender identity?" may be a better question than "How can I assist you in your transition?"

The FACT acronym may be helpful for healthcare providers. Providers should:

Training office staff to increase their knowledge and sensitivity toward transgender persons will also help facilitate a positive experience for patients. Additional guidelines for creating a welcoming office environment for transgender patients have been developed by the Gay and Lesbian Medical Association and can be found online at http://www.glma.org.

Nurses are in a unique position to provide care for transgender patients because the nursing model is holistic and patient-centered. However, the nursing profession requires more awareness of issues facing LGBT individuals, and nursing organizations have lagged behind other professional organizations representing physicians, psychologists, and social workers in promoting the care of LGBT individuals [67]. While it is necessary to educate nursing students on the unique healthcare needs of the LGBT community, there are no standards in place to assure these topics are taught in nursing school curricula. In 2010, the National Student Nurses Association adopted a resolution to include LGBT content in nursing school curricula to improve cultural competence. The Association adopted additional LGBT-affirming resolutions in 2015, 2016, 2019, and 2024; in 2021, it adopted a resolution in support of gender-affirming healthcare practices [68]. Recognizing the importance of addressing LGBT health needs as a matter of justice and equity, this group also adopted a 2012 resolution in support of The Joint Commission's LGBT field guide [69].

Electronic health records are typically not transgender friendly [47]. Products that pre-populate an individual encounter with a sex-specific history, exam, or ordering template will prevent the provider from accurately documenting care [70]. In response to the limitations of currently available electronic health records, the WPATH convened an Electronic Medical Records Working Group to make suggested guidelines for electronic health records developers. This group recommended that the patient's preferred name, gender identity, and pronoun preference be included as demographic variables and that the system effectively notify providers and staff of the preferred name and pronoun. Electronic health records should also provide a way to maintain an inventory of a patient's transition history and current anatomy and to effectively be able to change over time without negatively affecting the rest of the patient history [70].

In addition to concerns about how a patient's demographic information is listed, such as official versus preferred name, gender, and pronouns, providers need a way to accurately chart which organs a patient may or may not have. The electronic health records should not be limited or defined by the patient's assigned sex. The WPATH gives the following example [70]:

The WPATH is composed of diverse professionals with the mission to promote evidence-based care, education, research advocacy, public policy, and respect in transgender health. Since 1979, the group has published Standards of Care for the Health of Transsexual, Transgender, and Gender Non-Conforming People, with eight editions published as of 2024 [71].

The WPATH Standards of Care provide clinical guidelines for the provision of mental health care, hormone therapy, reproductive health, voice and communication therapy, surgery, postoperative care, and lifelong preventive and primary care [71]. The Standards of Care are intended to be flexible to meet individuals' needs, but some critics consider them to be overly restrictive and inflexible [57].

An alternative to the WPATH Standards of Care is the informed consent model. Under this model, after a discussion between the patient and the provider in which the risks, benefits, and alternatives to treatment are discussed, treatment can be provided. The provider determines whether the patient understands the risks and benefits and is competent to consent to treatment. With this model, a letter from a mental health professional is not required for treatment; psychotherapy is an option, not a requirement, for accessing health care. This removes a layer of gatekeeping that may be a barrier to care.

While an increasing number of providers and clinics use the informed consent model for hormone therapy, American surgeons provide GCS based on the WPATH guideline. Insurance providers also generally require adherence to the WPATH Standards of Care in order to consider GCS to be medically necessary.

The WPATH Standards of Care recommend that the diagnosis of gender dysphoria be made by a mental health professional with a minimum of a Master's degree, with knowledge about gender variation, competence in using the DSM, and the ability to diagnose co-existing mental health concerns [71]. They also suggest that healthcare professionals assessing transgender and gender diverse adults seeking gender-affirming treatment liaise with professionals from different disciplines within the field of transgender health for consultation and referral, if required. In the case of children and adolescents, the professional should have training in child and adolescent development and psychopathology. The WPATH guideline does not require a referral from a qualified mental health professional before initiating hormone therapy but strongly encourages this practice. Because of this, it is estimated that 84% of transgender individuals have received counseling related to their gender identity [39]. Generally, counseling results in a diagnosis of gender dysphoria.

While obtaining a referral for hormone therapy is the main reason that transgender individuals seek psychological therapy, other reasons include understanding the meaning of their feelings; whether to externally express those feelings; coming out to self, work, and family; seeking to network following a negative experience; or following up on information obtained on the Internet. In some cases, an individual may have been "caught" expressing his or her gender variance by a spouse or significant other or when there has been a program on transgender issues in the popular media [72]. Coming out trans is a time of heightened vulnerability [73]. Not everyone transitions. Some learn to live comfortably in their role consistent with their assigned birth sex, and others may transition partially or totally [7].

Transgender and gender non-conforming people face barriers to mental health care. The individual may fear being stereotyped or pathologized, as well as fearing judgment, prejudice, or discrimination. Some individuals object to common therapeutic practices, such as speaking in group therapy sessions or taking medications. Many mental health providers lack knowledge about transgender issues, and patients may object to having to educate their providers. Some patients feel their mental health providers focus too closely on their gender issues without regard to other concerns, such as anxiety. Finally, some mental health providers are openly unsupportive or hostile to transgender clients [180].

The first counseling visit with a transgender person is of great importance [72]. It is imperative that the counselor obtain as much information as possible during the initial intake, including a sex history, screening for sexual trauma, suicidal ideation, and history of self-harm. It is important to determine when the patient last saw a medical provider, whether he or she is taking hormones, and if so, who is prescribing them. It is also vital to assess the support system and screen for other mental health issues.

Additionally, the mental health professional should screen for conditions that have similar features to gender dysphoria, such as body dysmorphic disorder [17]. It is estimated that as many as 50% of MTF individuals have a history of what were previously described as other "Axis I disorders," and a significant percentage of MTFs also report a history of substance abuse, body image disturbances, and eating disorders [42].

The National Institute for Health and Clinical Excellence recommends that local care pathways should be created that that promote access to services for all transgender adults with autism.

(https://www.nice.org.uk/guidance/CG142 Last Accessed: July 26, 2024)

Level of Evidence: Expert Opinion/Consensus Statement

Common diagnostic presentations in transgender individuals include anxiety, depression, conduct disorder, oppositional defiant disorder, autism spectrum disorder, substance use disorder, and dissociative disorder [72]. The incidence of autism spectrum disorder has been found to be 10 times higher in the population of gender dysphoric individuals than in the general population [74]. In a major study of MTF individuals, more than 50% had suffered from major depression at some point in their life, as opposed to 19.6% in the general population [42]. In a review of the literature on depression in transgender individuals, Rotondi concludes that this is a multifaceted condition, with the common causative factors being: discrimination, disclosure, identity support, hormones and GCS, sociodemographics, socioeconomic factors, substance use, and access to health and social services [75]. Transgender individuals commonly report victimization and post-traumatic stress disorder, systemic stressors, and depression [76]. Interestingly, when a gender identity is truly and authentically affirmed, some of these conditions resolve [72].

In a Japanese study of 579 MTF and FTM patients of a national gender clinic, the majority of subjects had no psychiatric comorbidity [77]. Of those who did, the majority were MTF individuals. However, even among the subjects without current psychiatric comorbidity, 71.8% had thought seriously about suicide and 30.6% had performed self-mutilation [77]. In transgender individuals, self-harm may include cutting or injuring the breasts or the genitals [44,72].

There is some evidence that transgender individuals may have a higher incidence of personality disorders. In one study, 52% of a sample of 50 transgender patients had a personality disorder, regardless of MTF or FTM status [78]. The most prevalent diagnosis was narcissistic personality disorder. In contrast, the incidence of personality disorder in the general population is 15%.

As mentioned, there is an increased incidence of autism spectrum disorder in gender-variant children. A 2019 study found that characteristics of autism were associated with increased incidence in gender variation in a nonclinical community sample of children 6 to 12 years of age. This association was mainly attributable to deficits in social orienting and stereotyped behaviors. This study also documented higher levels of gender variance among children with parent-reported diagnoses of autism spectrum disorder, sensory processing disorder, or oppositional defiant disorder [181].

The University of California, San Francisco, recommends that transgender and gender non-conforming patients' routine primary care visits should include screening for co-occurring mental health conditions, past treatments, and history of suicide and self-injurious behaviors, symptoms of post-traumatic stress, and substance use. Primary care providers should be equipped to handle basic mental health needs of transgender patients (e.g., depression and anxiety) just as any other patient.

(https://transcare.ucsf.edu/sites/transcare.ucsf.edu/files/Transgender-PGACG-6-17-16.pdf Last Accessed: July 26, 2024)

Level of Evidence: Expert Opinion/Consensus Statement

Research on the incidence of suicide in transgender people is scarce, but transgender people are believed to have similar suicide risks as other people who experience major life changes, relationship difficulties, chronic medical conditions, or discrimination on the basis of minority status. The incidence of suicide ideation is as high as 64% and suicide attempts as high as 38% in the adult transgender population [76]. These rates are significantly higher than in the general population [76]. Predictors of suicide among transgender individuals are similar to those of the general population, most notably previous suicide attempts or near attempts, past psychiatric hospitalizations, and past psychiatric treatment. Parental rejection is one of the highest risk factors for suicide among transgender youth [73].

It has been suggested that MTF individuals may be at increased risk for eating disorders due to estrangement from body, biological gender, and expected social role. However, in a study of 40 MTF individuals in the United Kingdom, researchers found no support for this hypothesis [79]. They administered the Eating Disorder Inventory to patients preoperatively and six months postoperatively. While the MTF group showed higher levels of body dissatisfaction preoperatively than biologic women, this level was significantly lower postoperatively. On the "drive for thinness" subscale, the MTF group scored similarly to biological males and lower than biological females. This did not change postoperatively. Also, scores on bulimia subscales were lower in the MTF group than in gender-conforming men or women [79].

Fraser has worked in counseling using a non-pathologizing, trans-affirming model of transgender identity for 37 years and observes that many transgender people, aside from a mismatch between body and mind, seem quite healthy given the challenges of their condition [7]. Issues that arise in working with transgender individuals are the same as for the general population: issues of self, self in relation, autonomy and connection, identity, and intimacy.

There is little research on the effect of disclosure of transsexualism on relationships. Female partners of FTM persons report experiencing confusion regarding their own sexuality, relationship, patterns of interaction, and future following disclosure. Female partners of MTF individuals often respond to their partners' disclosure with profound shock and confusion, specifically their sexual identity and relationship uncertainty, MTF decision making, and public presentation. Concerns may arise regarding marginalization, finding acceptance as a couple, and being viewed as lesbian. Examples of activities that are supportive include open communication, maintaining a positive mood, social networking, social activism, impression management, and positive self-talk [15].

There is also a paucity of research on children of transgender parents. There is some evidence that the younger a child is when he or she is informed that a parent is transitioning, the better the outcome and the better the parent-child relationship. A healthy parent-child relationship at the time of transition tends to result in a healthier long-term relationship [80].

The goal of hormone therapy is to reduce the unwanted secondary sex characteristics of the original gender and to induce the development of secondary sex characteristics of the desired gender. Hormone therapy has also been found to enhance the person's sense of self and well-being [81]. Criteria for hormone therapy include persistent, well-documented gender dysphoria, a capacity to give informed consent, age of majority, and control of any significant medical or mental health issues [71]. In accordance with the WPATH guideline, it is recommended, though not required, that the decision to initiate hormone therapy be made in consultation with a qualified mental health professional [71].

There are no randomized clinical trials designed to determine the optimal regimen for cross-sex hormone use. The formulations and dosages employed are derived from experience treating hypogonadism [17]. In the case of MTF individuals, hormone therapy might include an anti-androgen, an estrogen, and in some cases, a progesterone component. In FTM individuals, hormone therapy is primarily testosterone. Gonadotropin-releasing hormone (GnRH) agonists can be used for both MTF and FTM individuals to reduce the amount of innate hormones secreted. GnRH agonists initially stimulate and then depress luteinizing hormone (LH) release from the pituitary gland. In the MTF individual, they reduce the serum concentration of testosterone to the castrate range within one week, and in the FTM individual, they stop the ovaries from making estrogen. Examples of GnRH agonists include leuprorelin, triptorelin, and goserelin [17]. However, these medications are expensive and require subcutaneous injections every 4 to 12 weeks. Prior to initiation of hormone treatment, storage of gametes should be discussed with the patient.

Many transgender patients hope for maximum doses of hormone treatment for transition as fast as possible, while others desire to proceed slowly in order to have more control over the effects or to present in a more androgynous way. Some MTF individuals want to maintain the ability to have erections, while others want to eliminate them [82]. Hormone therapy should be individualized based on the patient's goals, keeping in mind that hormone therapy is recommended in conjunction with some, but not all, surgical treatments for gender dysphoria [71].

Some transgender individuals obtain hormones from non-traditional sources, including the Internet, friends, and street vendors. In an urban environment, the prevalence of unsupervised hormone use in MTF individuals ranges from 29% to 63% [56]. This exposes patients to significant health risks from needle sharing, inappropriate dosing or combinations of hormones, and lack of screening for potential side effects such as thromboembolism [56].

When transgender individuals seek hormones, some providers will require an initial visit to conduct a thorough history, physical, and laboratory tests; provide referrals for mental health if needed; obtain informed consent; and provide appropriate vaccinations and a skin test for tuberculosis. Hormones are then prescribed at the second visit. Follow-up visits should take place every two to three months for the first year, after which patients can be seen every 6 to 12 months [71].

The Tom Waddell Health Center in San Francisco uses the following protocols for the initial visit for a patient seeking hormone therapy [82]:

In addition to the laboratory studies recommended by the Waddell protocols, initial laboratory studies prior to initiating hormone therapy might include prostate-specific antigen, glucose, electrolytes, thyroid-stimulating hormone, and perhaps testosterone and estradiol levels.

At some point in transition, transgender individuals typically seek surgical interventions to meet their goals to masculinize/feminize the body. Although obtaining a true estimate of the number of individuals undergoing surgical procedures as part of gender transition is difficult, available research indicates that more transgender patients are having surgery [114]. The American Society of Plastic Surgery's 2018 annual report included 2,885 MTF and 6,691 FTM patients undergoing GCS, an increase of 61% and 22%, respectively, compared with 2017 [115]. In addition, many surgeries are performed by other surgical subspecialties (e.g., urologists, obstetricians/gynecologists, maxillofacial surgeons). A large-scale survey found that among FTM individuals, 21% had chest reconstruction, 8% hysterectomy, 1% metoidioplasty, and 1% phalloplasty; among MTF individuals, 10% had vaginoplasty or labiaplasty, 9% orchiectomy, 8% augmentation mammoplasty, and 6% facial surgery [114].

The WPATH guideline suggests criteria for surgery for transgender individuals. The criteria for adults include [71]:

Hormone therapy is not a prerequisite, but at least six months of hormone treatment, or a longer period if required, unless hormone therapy is either not desired or is medically contraindicated, is recommended in the case of MTF individuals seeking augmentation mammoplasty, as this will result in better surgical (aesthetic) results.

Occasionally, patients may have unrealistic expectations about what it means to be a member of the opposite sex; it is important that these are brought to light before surgery is done. The real-life experience has been shown to reduce gender dysphoria and improve social and sexual functioning [18].

Very little has been published regarding the unique ongoing healthcare needs of patients who have undergone gender confirmation. In general, health care should be based on the treatments the patient has received and at what stage he or she may be in the gender transition. Health promotion awareness and health screening will vary somewhat, but generally the patient will have the same needs as most adult patients in a primary care setting; the patient's gender confirmation process will have little effect on many aspects of health care [81]. Basic preventive services, like sexually transmitted infection testing and cancer screening, can be provided without specific expertise in transgender care [57]. Keep in mind that in some cases, older transsexual individuals may not disclose their transgender history to their healthcare providers, as they initially sought treatment at a time when it was common for providers to use very strict guidelines to determine who could and could not receive treatment [30].

ROUTINE CARE FOR FTM PATIENTS

For the FTM patient, any residual female organs will require lifelong modified physical exams and risk screenings. These patients may require occasional modified pelvic exams and/or mammograms, and both the provider and the patient may have difficulty finding a comfortable clinical environment [37]. For FTM individuals, gynecologic examinations can heighten their emotional conflict between self-perception and physical anatomy. Respectful communication that maintains dignity, agency, and control is central to mitigating distress during pelvic exams [146]. The routine physical exam should include a breast exam, Pap test, and assessment of bone health and other possible effects of long-term testosterone supplementation.

Breast Exam

Among FTM individuals who have not had a mastectomy, the risk of breast cancer is likely similar to cisgender females. Those who have had mastectomy seem to have a lower risk of breast cancer, possibly due to GCS, but this is based on limited research [151]. Excess exogenous testosterone can be converted to estrogen, which has been linked to breast cancer [152]. As such, regular examination of remaining breast tissue is indicated. Although a mastectomy may have been performed, the axillary lymph nodes should be examined for enlargement. If a mastectomy has not been performed, annual mammograms are recommended.

Pap Test

The pelvic exam may be a traumatic and anxiety inducing procedure for transgender men and other trans-masculine persons. Transgender men are less likely to be up to date on cervical cancer screenings and have a higher rate of inadequate cytologic sampling. Should the individual express distress or concern about the examination, it may be deferred until a later date once a trusting relationship has been developed.

(https://transcare.ucsf.edu/sites/transcare.ucsf.edu/files/Transgender-PGACG-6-17-16.pdf Last Accessed: July 26, 2024)

Level of Evidence: Expert Opinion/Consensus Statement

For patients using androgen therapy who have not had a complete hysterectomy, there may be an increased risk of endometrial and ovarian cancer [57]. Therefore, a regular Pap test is indicated. It is important to be sensitive when performing a pelvic exam on a transsexual man. As noted, FTM individuals often experience emotional and psychological distress with pap testing due to gender dissonance. This may be given as a reason for avoiding gynecologic examinations altogether [146]. It may be difficult to get a good sample, as the cervix will be atrophic; intravaginal estrogen cream can be used a few days prior to the Pap test to improve results.

Other interventions to consider are the use of a pediatric or long, narrow speculum; use of non-interfering lubricant on the speculum; application of topical lidocaine to the vaginal introitus; and informing FTM individuals of the likelihood of Pap test results being unsatisfactory [153,154]. In some cases, providers may consider the use of sedative-hypnotics (e.g., benzodiazepines) prior to testing [154].

Long-Term Effects of Testosterone Therapy

Aging FTM patients may have an increased risk of cardiovascular disease and diabetes due to the effects of long-term testosterone and should be screened accordingly [30]. A small amount of research indicates that FTM individuals on long-term testosterone therapy do not have an increased risk of low bone mass [155]. Part of testosterone is converted to estradiol at levels that will support bone mineral density [99]. Dual-energy x-ray absorptiometry screening is suggested for FTM individuals older than 65 years of age, or after 50 years of age if not on testosterone [156].

With greater public awareness of transgender issues, more adolescent and pre-adolescent children are expressing a desire to be a member of the opposite sex. While gender dysphoria in children does not necessarily continue into adulthood, its persistence into adolescence increases the likelihood that it will continue [71]. In the United States, informed consent laws prevent minors from consenting to their own medical treatment until 18 years of age unless they have the consent of a parent or guardian [159]. Because of this, providers traditionally waited to provide treatment until transgender children reached the age of legal consent to medical treatment, even though these adolescents made it clear that they found their pubertal physical changes unbearable [21]. Gradually, some providers have decided to treat individuals younger than 18 years of age with hormones to either suppress puberty or bring about the physical changes of the desired gender, provided there is parental consent. Multidisciplinary teams in the Netherlands have been pioneers in the treatment of transgender children [160].

When transgender children begin school, they begin to suppress cross-gender activities, as pressure from peers, parents, and schools quickly represses these unwanted behaviors. Children then become secretive. The behavior can be changed, but the internal sense of gender remains. However, for 75% to 80% of children who exhibit gender dysphoria, the disorder does not persist into adolescence, and complete gender role change and hormone treatment is not recommended in prepubertal children [17].

The American Academy of Child and Adolescent Psychiatry recommends that clinicians should be aware of current evidence on the natural course of gender discordance and associated psychopathology in children and adolescents in choosing the treatment goals and modality. It is important to distinguish those who display only variation in gender role behavior (gender nonconformity, which is not a DSM diagnosis) from those who also display a gender identity discordant from their socially assigned birth gender and biologic sex.

(https://www.jaacap.org/article/S0890-8567(12)00500-X/fulltext. Last Accessed: July 26, 2024)

Level of Evidence: Expert Opinion/Consensus Statement

In general, psychological therapy and support can assist transgender children/adolescents to complete developmental tasks on schedule, achieve self-acceptance and understanding, and manage and cope with social problems (e.g., peer and/or family conflict) and the stress of the change process [159]. Three models of therapy for children who display gender dysphoria have been described. The first of these is affirming approaches, based on the concept that being transgender is not a mental illness [28]. This approach encourages the child's exploration of gender identity and assists the child and his or her family to explore interventions such as social transitioning and hormone therapy. Dreger defines this approach as the "accommodation" mode [161]. The second treatment approach involves supportive therapies—a "wait and see" approach to determine how the child's gender identity unfolds. With this approach, there are no gender-related interventions. The third approach is a "corrective" approach that seeks to align the child's gender identity with his or her biological sex. This approach is also described by Dreger as the "therapeutic" model that views the child's gender dysphoria in terms of familial dysfunction and seeks to guide the child into a less stressful, more sustainable family environment and gender identity [161]. This last approach has been generally dismissed or condemned by organizations like the APA [162].

In a qualitative study of FTM individuals, an early childhood sense of body-mind dissonance was the first sign of a transgendered identity [163]. Specifically, young FTM individuals believe themselves to be boys, prefer to play as boys, and balk at imposed feminine dress. This resulted in feelings of anger, frustration, and confusion for children as well as their parents. In American society, female children are often allowed more latitude in their dress, mannerisms, and play. The label of "tomboy" does not carry the same stigma that the label "sissy" carries for boys. As a result, in FTM individuals, gender dysphoria tends not to become an issue until puberty, with the onset of unwanted physical and emotional changes. At this time, FTM individuals often describe female secondary sex characteristics and menstruation as "repugnant" and "humiliating" [163].

In MTF individuals as well, gender dysphoria generally intensifies when adolescents develop unwanted secondary sex characteristics. Many gender dysphoric adolescents actually begin living in their true gender upon entering high school and desire hormones and surgery at that point. High levels of emotional distress, major depression, suicidality, and gender-related psychological and physical abuse during early adolescence were reported in a large study of MTF individuals [42]. The depression is thought to be a product of the strain and confusion associated with forming a sexual identity that is at odds with societal norms. This research strongly suggests that psychological and physical abuse play a major role in the incidence of depression.

While suicide is the second leading cause of death among adolescents in the United States, transgender adolescents are at higher risk for suicide when compared with cisgender adolescents. An estimated 34% of transgender adolescents report experiencing suicidal ideation in the past year, 61% report suicidal ideation during their lifetime, and 30% to 51% report at least one suicide attempt. Transgender adolescents assigned female at birth were at the highest risk for suicidal ideation and attempt [186].

Mallon and DeCrescenzo provide an overall review of the developmental needs of transgender children and adolescents and offer many suggestions for responding to the child in a healthy manner [164]. One such suggestion is that parents develop a "script" they can use to answer questions from neighbors and friends to decrease the possibility of harm to a transgender child. Because many transgender children who are not met with empathy and compassion become runaways or end up in foster care or the judicial system, much education needs to be done in these arenas as well.

Although it may be difficult for a parent to come to terms with having a transgendered child, it is possible; most parents report a resiliency beyond what they had imagined [116]. Parents worry about facing rejection by their families and the community and a general fear of the unknown. Despite these fears, many parents eventually accept their child's transition. For parents, a successful transition entails holding onto the essence of the love they had for their child and the moral worth of their child [116]. Parents who struggle with feelings related to their child's transgender identity could benefit from joining a support group of other parents of transgender children in order to obtain education, perspective, and strength from those who have faced similar challenges. These parents can then be a better resource for their children and more effectively engage in honest and open dialogue [116].

MEDICAL TREATMENT

Notice

Since 2021, several states have passed laws limiting or banning gender-affirming care for patients younger than 18 years of age; some states have proposed limiting care in patients up to 26 years of age. As always, it is important that healthcare professionals consult state board rules and laws governing their practice to ensure they are practicing legally.

Medical interventions for transgender children and adolescents fall into three categories or stages: fully reversible interventions, which include puberty-suppressing hormones; partially reversible interventions, which include cross-gender hormones; and irreversible interventions, which are surgical procedures. It is recommended that treatment progress from one stage to another with enough time for the patient and their family to fully integrate the effects of each stage [71].

The Endocrine Society suggests that adolescents who meet diagnostic criteria for gender dysphoria/gender incongruence, fulfill criteria for treatment, and are requesting treatment should initially undergo treatment to suppress pubertal development.

(https://academic.oup.com/jcem/article/102/11/3869/4157558 Last Accessed: July 26, 2024)

Level of Evidence: Weak recommendation based on low-quality evidence

Some providers believe that adolescents with gender dysphoria should experience the initial changes of their biologic, spontaneous puberty because their emotional reaction to these first physical changes has diagnostic value. However, to these youth, experiencing full biologic puberty is undesirable. Not stopping the development of secondary sex characteristics may result in emotional impairment, and the physical outcome following intervention in adulthood is less satisfactory than intervention before puberty, creating lifelong disadvantages. In males, these permanent changes include the development of laryngeal prominence, low voice, large jaws and brow, large stature, and male hair patterns. In females, these changes include short stature and large breasts. Pubertal suppression maintains end-organ sensitivity to sex steroids observed during early puberty, enabling satisfactory cross-sex body changes with low doses and avoiding irreversible characteristics that occur by mid-puberty [17]. By blocking, delaying, or "freezing" puberty, time is "bought" for providers to thoroughly explore the child's request for GCS [21]. The WPATH recommends commencing treatment when adolescents have reached early-to-advanced puberty (Tanner stage 2 to stage 4) [71].

Suppressing the effects of puberty is commonly done with GnRH agonists. GnRH agonists, commonly goserelin and leuprolide, initially overstimulate the secretion of gonadotropin, during what is called the flare period. Ultimately, this down-regulates and inhibits the secretion of gonadotropin, which in turn inhibits release of LH and FSH. In males, this suppresses the production of testosterone and sperm. In females, this suppresses ovulation and estrogen production.

GnRH agonist administration should begin before it is too late to reverse the physical changes of puberty. This is possible during Tanner stage B3 (breast bud extending beyond areola) in girls and during Tanner stage G3 (increase in testicular volume of ≥4 mL, with measurable nocturnal testosterone values) in boys. After testosterone production commences (testicular volume ≥10 mL), virilization becomes irreversible [18].

Prolonged pubertal suppression using GnRH agonists may continue for a few years. The effects are reversible and should not prevent resumption of pubertal development if treatment is stopped. In males, spermatogenesis will resume, along with the development of male secondary sex characteristics. In females, ovulation will occur, though there are not enough data to predict the timing [17]. There are no good data yet of the long-term effects of leuprolide on children with gender dysphoria, but the effect of GnRH agonists on bone density is being studied [161]. Due to the delay in bone density accrual in patients undergoing pubertal suppression, healthcare providers are advised to follow the patient's bone health annually and to consider annual dual-energy x-ray absorptiometry [165]. It is believed that when either cross-sex hormone therapy is initiated or biologic puberty is allowed to take place, bone mineral density will increase [21].

Laboratory work should be done prior to the initiation of therapy to establish baseline levels of gonadotropins, sex hormones, and metabolic determinants. This would include fasting glucose, cholesterol, and renal and hepatic studies. Measurements of height, weight, sitting height, hip and waist circumferences, and Tanner pubertal stage can be recorded initially and re-evaluated periodically to track growth and development [159].

To date, there seem to be no ill effects of GnRH agonists on social, emotional, and school functioning, but potential effects may be too subtle to observe during the follow-up sessions by clinical assessment alone [21]. One potential disadvantage in treating MTF individuals early in puberty is that the penis and testes will not fully develop, making surgical creation of a vagina from penile and scrotal tissue more difficult [71].

Some experts recommend initiating cross-sex hormone therapy at 16 years of age, using a gradually increasing dose schedule [17]. Others advocate using age 16 as a guideline but also considering starting cross-sex hormones earlier on a case-by-case basis after reviewing the potential risks and benefits with the youth and the parents [28]. The Fenway guidelines recommend that testosterone be commenced at 14.5 to 15 years of age for transboys and 13 to 14 years of age for transgirls [189].

In MTF individuals, hormone therapy would start with 17β estradiol at 5 mcg/kg per day and increase every six months to a maximum of 2 mg per day [28]. In FTM individuals, treatment starts with intramuscular injections of testosterone at 25 mg/m2 every two weeks, increasing the dose every six months to a maximum 100 mg/m2 every two weeks. At first, the dosage may not be high enough to suppress endogenous hormone secretion, so the recommendation is to continue treatment with GnRH agonists until gonadectomy is performed. Surgery should be deferred until individuals reach the legal age of majority and have lived continuously in their desired gender for 12 months. In the case of FTM patients, chest surgery could be carried out earlier, preferably after some time of living in the desired gender role and after one year of testosterone administration [71].

In the first year of cross-sex hormone therapy, patients should be monitored every three months, particularly while their hormone dosages are being adjusted, to maximize desired effects, minimize negative effects, and screen for complications [28]. Individuals may be monitored less often after they achieve stability in their dosing and are progressing well in their transition.

Beginning treatment for gender dysphoria at puberty appears to be associated with better psychological outcomes than beginning treatment in adulthood, by which time irreversible secondary sex characteristics may pose lifelong barriers to successful sex reassignment. Additionally, limited observational data from transgender youth have indicated that gender dysphoria is reduced and relationships and academic skills are improved when therapy is started early [18]. The first longitudinal study of 55 transgender youth (22 MTF and 33 FTM) who received puberty suppression, cross-sex hormones, and in some cases GCS, was performed in the Netherlands in 2014 [160]. The researchers reported that gender dysphoria and body-image difficulties persisted through puberty suppression but remitted after the administration of cross-sex hormones and GCS. None of the individuals reported regret during puberty suppression, cross-sex hormone administration, or after GCS. Psychological functioning improved steadily over time, and overall well-being was comparable to non-transgender peers. In fact, a higher percentage of the transgender study group was pursuing higher education than the general public. The researchers speculated that this success was not only due to the medical treatment but also due to access to care (covered by health insurance) and the involvement of a multidisciplinary team of mental health professionals, physicians, surgeons, and supportive parents [160]. Another follow-up study done in the Netherlands revealed that young transgender adults who completed puberty suppression, hormone therapy, and GCS as youth reported becoming more sexually active following these treatments, although as a group they were still less sexually active than their cisgender peers. The researchers concluded that many transgender youth begin their sex lives only after having received gender-affirming medical care [190].

Preservation of fertility is challenging for transgender individuals, and few transgender youths opt for fertility preservation. Reasons include developmental (age) barriers, cognitive barriers, cost, invasiveness, and provider knowledge. There are also ethical concerns centering on the principles of autonomy (e.g., parent/child decisional conflict about hormonal therapies and fertility preservation) and justice (e.g., prohibitive cost). If puberty suppression has occurred before endogenous puberty has occurred, options for fertility preservation are limited. For MTF youth, testicular tissue cryopreservation is an experimental fertility preservation option; no human births have been reported to date using this procedure. In FTM youth, ovarian tissue cryopreservation is a theoretical possibility. To date, this procedure has resulted in more than 100 live births [191].

Transgender care is generally lacking in medical school curricula. Among 132 U.S. and Canadian medical schools surveyed in 2011, the median reported combined hours dedicated to LGBTQIA content was five hours [166]. One-third of medical schools reported no hours of LGBT content during clinical years, and less than 40% of medical schools taught transgender-related content, such as GCS, body image, or transitioning, despite research that shows that medical students who have clinical exposure to LGBTQIA patients during their training perform more comprehensive histories, have a more positive attitude toward these patients, and possess greater knowledge of LGBTQIA healthcare concerns than students with little or no clinical exposure [56]. In addition, the results of one survey indicate that, contrary to official American Public Health Association policy, public health schools seldom offer planned curricula that address comprehensive LGBT health [167]. Barriers to increased transgender health exposure include limited curricular time, lack of topic-specific competency among faculty, and underwhelming institutional support [168].

Coverage of transgender care is also lacking from most nursing education. A review of the top 10 nursing journals from 2005 to 2009 found only eight articles (out of nearly 5,000) that focused on LGBT issues and only one that mentioned transgender issues [169]. None of the eight articles came from U.S. researchers. As stated, in 2010, the National Student Nurses Association adopted a resolution to include LGBT content in nursing school curricula to improve cultural competence, with additional resolutions adopted in 2015, 2016, 2019, and 2021 [68].

The American Association of Colleges of Nursing's The Essentials of Baccalaureate Education for Professional Nursing Practice does not directly address transgender health in the curriculum [170]. Likewise, the Quality and Safety Education for Nurses initiative excludes transgender issues as well [171].

The consensus model for Advanced Practice Registered Nurse (APRN) Regulation includes six populations for APRN licensure: adult/gerontology, pediatric, neonatal, family/individual, psychiatric/mental health, and women's health/gender-related [172]. In 2021, Columbia University School of Nursing launched the first certification program for professional achievement in transgender/gender non-binary health care for nurse practitioners; it has since been expanded to include physician assistants/associates [194]. The American College of Nurse-Midwives supports the WPATH guideline and expects midwives to become knowledgeable about the healthcare needs of transsexual, transgender, and gender non-conforming people. With proper training, midwives may provide hormone therapy for transgender individuals [173].

Fifty percent of transgender individuals surveyed reported having to teach their medical providers about transgender care [72]. Having transgender people educate medical students will not transform the healthcare delivery system to accept transgender persons [63]. Instead, active participation by transgendered individuals in public health research, policy making, and teaching healthcare providers techniques to provide acceptable care is recommended. The ACA has provided funding for LGBT cultural competency trainings, which have been implemented in the health departments of large cities, with training underway for staff of the National Health Service Corps [59].

Transgender individuals have unique health needs. This population exhibits a high prevalence of HIV and other sexually transmitted infections, victimization, mental health issues, and suicide. In addition, transgender individuals are less likely to have health insurance than heterosexual or LGB individuals. Improving the health of sexual minorities is a goal of Healthy People 2030, which calls for recognition of transgender health needs as medically necessary and points out that transgender care is virtually absent from medical and nursing school curricula. This course has provided a basic overview of the care of individuals experiencing gender dysphoria. With this information, it is hoped that healthcare professionals will address the unique healthcare needs of transgender individuals, overcoming the barriers to care and providing these patients with the best and most sensitive care possible.