Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Transgender Medicine
Definition and Epidemiology
Gender identity is the internal sense of one’s own sex, whether male, female, neither, both, or something else. Transgender is a broad term to reference individuals with gender identity that differs from sex recorded at birth, typically based on external genitalia ( Table 215-1 ). In the United States, an estimated 0.6% of adults, or approximately 1.4 million individuals, are transgender. Cisgender describes individuals with gender identity that aligns with recorded sex at birth. Other terms with similar meaning to transgender include trans, gender incongruent, gender nonbinary, gender diverse, and genderqueer—all terms being adjectives for people with gender identity that is not aligned with visible anatomy at birth. The latter three terms reference people who are less binary in their sense of their sex identity. The term transsexual is an older word that previously referenced transgender individuals who had “completed” planned treatment to change their bodies to better align with their gender identities.
TABLE 215-1
DEFINITION OF GENDER TERMS
Adapted from Safer JD, Tangpricha V. Care of transgender persons. N Engl J Med . 2019;381:2451-2460.
| Sex/Gender: Umbrella terms to reference biologic characteristics, identification, and stereotypical behaviors that are considered male, female, or some variation. The word gender is sometimes used as a synonym for the word sex in colloquial use and is also sometimes used as shorthand for either gender identity or gender expression. |
| Gender Identity: Internal sense of one’s own sex as male, female, both, or neither. |
| Gender Expression: How an individual communicates gender identity to themselves and others. |
| Transgender, Transsexual, Trans, Gender Diverse, Gender Nonbinary, Gender Incongruent, ∗ Genderqueer: Adjectives for individuals with a gender identity that is not aligned with sex recorded at birth. |
| Cisgender, Nontransgender: Adjectives for individuals with a gender identity that is aligned with sex recorded at birth. |
| Gender-Affirming/Gender-Confirming Hormone Treatment and Surgeries: Medical interventions for transgender and gender-diverse individuals to align gender identity better with other physical characteristics. |
| Intersex: A term for people with sexual and/or reproductive anatomy that is not typical (may also be labeled people with differences of sexual differentiation). |
∗ This term is replacing the term gender dysphoria to label the lack of alignment for some individuals between their gender identity and their sex as recorded at birth.
Pathobiology
Historically, being transgender was considered a mental health problem with a mental health solution. Indeed, the term gender dysphoria has been used for a transgender person whose gender identity is associated with clinically significant distress or impairment in social, occupational, or other important areas of functioning. However, not every transgender or gender-diverse individual experiences dysphoria, including transgender people seeking medical treatment. Further, some transgender people will suffer clinical dysphoria independent of their being transgender. In the former case, a transgender person might be treated with gender-affirming hormones or surgeries. In the latter case, a person may need mental health approaches to the clinical dysphoria independent of any need for gender-affirming medical intervention. Thus, the International Classification of Diseases , 11th edition removes the term gender dysphoria entirely and adds the term gender incongruence to a new sexual health section.
The current model is that gender identity is a biologic phenomenon that cannot be influenced externally. Data for the biologic underpinnings to gender identity include evidence from studies of people who are intersex or have differences of sexual differentiation, evidence from twin studies, evidence from studies of the impact of prenatal androgen exposure, and evidence from studies of certain neurologic structures. For example, among XY children with cloacal exstrophy ( Chapter 214 ), with or without penile agenesis and penile ablation, who are assigned female at birth, a substantial proportion are not comfortable with that designation.
When one identical twin is transgender, the other will also be transgender 40% of the time. By comparison the concordance rate among fraternal twins is zero or close to zero.
For XX chromosome individuals with virilizing congenital adrenal hyperplasia ( Chapter 214 ), male gender identity may be present in 5%, nearly 10-fold the rate of male gender identity among XX chromosome people in general. Among XY individuals with complete androgen insensitivity syndrome, nearly all have female gender identity. The implication is that some androgen action on the brain may be necessary for male gender identity and that increased in utero androgen exposure may confer male gender identity in some individuals. Even if some minimal androgen action on the brain proves necessary for male gender identity, it is not sufficient. There is no evidence that most transgender people have either excess or deficient exposure to androgens.
Studies of the brains of transgender individuals suggest a physical manifestation associated with gender identity. A postmortem study of six transgender women (male-to-female) found that the size of the bed nucleus of the stria terminalis in the hypothalamus was within the female range independent of historical hormone treatment. Brain imaging studies suggest that hormonally untreated transgender men exhibit white matter microstructure more typically male than female and that untreated transgender women exhibit white matter microstructure intermediate between cisgender male and cisgender female individuals.
Clinical Manifestations and Diagnosis
Children may articulate gender identity as early as age 2 years and proceed to demonstrate facility with gender labeling, including their use of pronouns, by school age. About 0.6% to 2.7% of children may report some degree of gender diversity. By adolescence, many children clearly articulate gender identity, such that adolescents who present as transgender people seeking gender-affirming treatment are overwhelmingly stable in their reported gender identity into adulthood. Puberty can be distressing for transgender children, with the “wrong puberty” serving as the trigger for some adolescents to report their gender identity to their parents and health care providers.
Most transgender persons present for gender-affirming medical intervention as older adolescents or adults, perhaps because of factors such as late recognition of gender identity, failure to articulate gender identity, or outside pressure to conform. Despite the older presentation, most transgender people report that, in retrospect, they were aware of their gender incongruence before puberty.
Transgender people present in heterogenous fashion. Some transgender people are confident in their sense of their gender identity and their treatment goals. Others may benefit from greater support from mental health providers, either to help articulate gender identity or to help with goals.
Clinically, being transgender is ascertained on the basis of history alone. The patient should have both persistent gender incongruence and the capacity to make treatment decisions. The requirement for persistence does not have a specific time frame, but typical presentations include clarity regarding gender identity that extend back years—indeed commonly as far back as childhood. Reports of recognition of gender incongruence over shorter periods should prompt further exploration of underlying factors and goals.
Transgender persons also have higher rates of mental health morbidity, including anxiety, depression, and suicidality, often as a result of social stigma rather than gender incongruence per se. Patients should be screened for both confounding mental health issues and the ability to engage safely in treatment. Some mental health conditions may interfere with the ability to provide a reliable history. For example, patients who present as transgender might instead have an obsessive compulsive disorder or well-masked psychosis rather than true gender incongruence. Since transgender persons also can experience mental health morbidity, including obsessive-compulsive disorder and psychoses, a multidisciplinary assessment must include a careful evaluation of mental health.
Any sufficiently knowledgeable clinician should be able to ascertain that an adult is transgender. The criteria for determining whether someone is transgender are the same for children and adolescents as for adults. However, due to challenges in how children articulate gender identity, guidelines recommend including mental health professionals for assessment of minors. Clinicians also should be able to identify mental health conditions that might confound the assessment or that should include input from mental health providers who can.
Treatment
Not all transgender persons seek medical treatment. Even among those who desire intervention, treatment may be deferred due to barriers that include family circumstance, work environment, or insurance coverage.
Persons who seek medical treatment for gender incongruence benefit from providers who can help set expectations about medical interventions. Primary care clinicians can initiate and manage transgender medical interventions, including both hormone therapy and other agents that affect hormone levels, with support from endocrinologists, if needed.
No convincing literature indicates any success or benefit from attempts to change a person’s gender identity. In fact, such effects to conform to sex norms result in demonstrably poorer psychosocial outcomes.
Mental health support is a key element of gender-affirming care. Clinicians must address mental health conditions that may confound assessment of gender identity and treatment goals.
The current strategies for gender-affirming hormone therapy for adult transgender patients primarily involve moving circulating testosterone levels up for masculinizing therapy and down for feminizing therapy. Typical agents are androgens to virilize transgender men and estrogens, in addition to other antiandrogens given as adjuncts, to reduce testosterone levels to the conventional female range for transgender women while maintaining estradiol levels in what is considered the typical female physiologic range.
Prior to beginning gender-affirming hormone therapy, clinicians should review the patient’s gender identity, treatment goals, and timing for therapy, with discussion of both social and health issues. Typical informed consent for shared medical decision making includes the potential risks and benefits of hormone therapy along with the time frame for expected changes. Clinicians should be knowledgeable about routine monitoring of hormone levels, monitoring of other relevant laboratory testing (e.g., serum potassium measurement for spironolactone treatment or hematocrit for testosterone treatment), and potential adverse outcomes. In the absence of specific data for transgender people, cancer screening is typically done on the basis of the tissues and organs present and informed by guidelines for the general population.
Hormone Therapy for Transgender Men (Female to Male)
Gender-affirming hormone treatment for transgender men (female to male) is very similar to hormone replacement therapy for hypogonadal cisgender men ( Chapter 216 ), with testosterone, usually starting at a dose that is about half the dose used for a hypogonadotropic cisgender man (see Table 216-6 ) and aiming for a goal testosterone level in the typical physiologic cisgender male range (300 to 1000 ng/dL). Testosterone can be administered orally, transdermally, or parenterally ( Table 215-2 ). The most popular products are testosterone enanthate or cypionate 50 to 200 mg weekly administered intramuscularly or subcutaneously. Higher doses (100 to 200 mg) can be administered every 2 weeks, but patients may not prefer the resulting greater periodicity in testosterone levels. Transdermal preparations such as testosterone gel (2.5 to 10 g/day) or a testosterone patch (2.5 to 7.5 mg/day) will achieve the same virilizing effects as intramuscular testosterone, but poor absorption may prove frustrating when trying to achieve goal testosterone levels. Also, testosterone patches may cause skin irritation. Although not widely used, oral testosterone undecanoate (160 to 240 mg/day) is also available. There is no indication for antiestrogens. Some patients, including some who identify as nonbinary, may ask to be treated with smaller doses of testosterone.
TABLE 215-2
TESTOSTERONE THERAPY FOR TRANSGENDER MEN (FEMALE TO MALE)
Adapted from Safer JD, Tangpricha V. Care of transgender persons. N Engl J Med . 2019;381:2451-2460.
| MEDICATION | DOSE | CONCERNS | COMMENTS |
|---|---|---|---|
| TESTOSTERONE | Erythrocytosis, which may unmask polycythemia that may require further evaluation | Screen for tobacco use, sleep apnea | |
| Acne can develop and/or be exacerbated | Acne, typically transient | ||
| Parenteral | |||
| Testosterone enanthate or cypionate | Start at 25 to 50 mg IM/SQ weekly or 50 to 100 every 2 weeks and titrate up to 50 to 100 mg IM/SQ weekly or 100 to 200 mg IM/SQ every 2 weeks | SQ or IM injections have been demonstrated to be equally effective | |
| Target levels are more easily achieved than with transdermal products | |||
| Weekly administration diminishes periodicity | |||
| Monitor levels either with peaks (at 24-48 hours) and troughs (immediately prior to next dose) or with mid-dose measurement | |||
| Testosterone undecanoate | 1000 mg IM every 12 weeks | Oil embolism is a rare adverse event | |
| Transdermal or Transbuccal | |||
| Testosterone gel | Start at 25 mg/day and titrate up to 50 to 100 mg/day | Risk of transfer to others | Uniform levels |
| Target levels may be harder to achieve than with parenteral products | |||
| Testosterone patch | Start at 2 mg/day and titrate up to 8 mg/day | Skin reactions are common | Uniform levels |
| Target levels may be harder to achieve than with parenteral products | |||
| Testosterone buccal patch | 30 mg to gums every 12 hours | Inconvenience of preparation may limit use | |
IM = intramuscular; SQ = subcutaneous.
Although the exact effects and time course of testosterone will vary from patient to patient, responses to treatment include increased facial/body hair, male-pattern balding, increased acne, increased libido, increased muscle mass, clitoromegaly, deepening of the voice, and redistribution of fat within the first 3 to 12 months of testosterone therapy. Menses cease in the majority of individuals within 6 months of initiating treatment. Although circulating sex hormone is needed for optimal bone health, there is no known health reason to prefer a typically male hormone profile versus a typically female hormone profile, or something in between. Even low-dose hormone treatment can have dramatic physical consequences for some people. Patients should be counseled and asked to state their desired outcome before beginning treatment.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here