Transgender Care: Providing Inclusive and Compassionate Healthcare Services

A healthy 19-year-old college student declares that he is transgender and wants to begin hormone therapy. The sex recorded at birth is female, but he notes having identified as a boy for as long as he can remember.

More recently, his treatment goals have become clearer, including a desire to begin treatment and present as a man. He has no medical or behavioral health issues and takes no medications. How would you advise this patient?

“Gender identity” is the term used to describe a person’s feeling of being male, female, neither, or some combination of both (Table 1). The terms "transgender", "transsexual", "trans", "gender non-binary", "gender incongruent", and "gender queer " are adjectives for people with gender identities that do not align with the sex registered at birth. "Cisgender" is the term used for people who are not transgender, that is, people whose sex recorded at birth aligns with their gender identity.

Transgender men have a male gender identity and were registered as female at birth. Transgender women have a female gender identity and were registered at birth as men. Gender non-binary people do not identify as men or women or have characteristics of both sexes.

Gender expression relates to the way a person communicates their gender identity. Efforts to align physical characteristics with gender identity may be called transitioning, gender affirmation, or gender confirmation.

Gender dysphoria is a mental health diagnosis that describes the discomfort felt by some people when their gender identity and sex recorded at birth do not align. Not all transgender people have dysphoria. However, many US insurance companies require a diagnosis of gender dysphoria for reimbursement for transgender-related medical and surgical interventions.1

Although being transgender is not a behavioral health condition , the codes for the diagnosis of transgender are in the mental health section of the International Classification of Diseases, Ninth Revision (ICD-9), and Tenth Revision (ICD-10). ). The plan for ICD-11 is to add the term “gender incongruence” to a new sexual health section and remove the term “gender dysphoria” from the document.2

Although the mechanisms that inform gender identity are unknown, current data suggest a biological basis programmed from birth.3-9 For example, there are reports of XY chromosome intersex people raised as female who report male gender identity,4, 5 and identical twin brothers of transgender people more likely than fraternal twin brothers of transgender people to be transgender.6 Associations between brain anatomy and gender identity have also been reported.9

Data from 2016 from the Centers for Disease Control and Prevention (CDC) Behavioral Risk Factor Surveillance System suggest that in the United States approximately 0.6% of adults, or 1.4 million people, identify as transgender.10 Many transgender people experience barriers to accessing health care and medical mistreatment.11-14

These barriers to care are believed to play a major role in health disparities between transgender and Cisgender people, with higher rates of substance abuse, infection, mental health conditions, and cancer in transgender people.11,12, 15-17 Improving access to healthcare will require the involvement of more general practitioners from specialized settings.18

> Presentation and evaluation

Children can label genders and articulate gender identity by age 2.19 In surveys, up to 2.7% of children may report gender incongruence,20 but many of these children do not continue to do so later in life. life.21

Most transgender people present to doctors in late adolescence or adulthood. While late presentation results from an inability to articulate gender identity, failure to recognize gender incongruence, or external pressure to conform is not known.

The desire to avoid the "wrong puberty" may be the catalyst for some adolescents to report their gender incongruence if they had not done so before.22 In retrospect, many transgender people reported that awareness of their gender incongruence began before puberty. .

Transgender identity is established based on history; Gender incongruence must be persistent, typically present for years.23

In addition to obtaining a social and sexual history, along with screening for infections if warranted by the sexual history, the clinical examination of transgender patients should include evaluation for anxiety, depression, and suicidality, which are more common among transgender people than in cisgender people.24

Any professional able to identify mental health conditions that may confound assessment can determine whether an adult patient meets the criteria for treatment.25 Rarely, patients who present as transgender actually have obsessive-compulsive disorder26 or a well-known psychosis. masked

Mental health care professionals should participate in the evaluation of adults if a mental health condition is suspected or identified and routinely participate in the evaluation of children and adolescents, who may articulate a more heterogeneous gender identity.25

Not all transgender people seek medical intervention. In an online survey, just over half of transgender people surveyed reported seeking hormonal or surgical treatment.27

There are several criteria for prescribing hormonal treatment. These include persistent gender incongruence, the ability to make informed treatment decisions, and reasonable control of associated mental health conditions.

> Transfeminine hormone therapy (from man to woman)

The conventional therapeutic goals for hormonal treatment in transfeminines are to reduce facial hair growth, induce breast development, and induce redistribution of fat and muscle to a more feminine pattern. Starting hormone therapy after puberty will not affect height or voice. Since terminal hair on the face continues to grow without androgenic stimulation, transgender women may require electrolysis or laser hair removal.

In the absence of data, the usual strategy involves using known physiological information as a surrogate target to achieve hormone levels that match gender identity, moving testosterone levels from the male range (300 to 1,000 ng per deciliter) to the female range. (<50 ng per deciliter) and target estradiol levels in the range of 100 to 200 pg per milliliter while avoiding supraphysiological levels (>200 pg per milliliter). Observational studies suggest that physical changes should be anticipated in 6 to 18 months.

Although orchiectomy is the most effective means of lowering testosterone levels, many transgender women opt for medical treatment instead.28

Estrogens suppress androgen production through a central feedback mechanism while inducing feminization and protecting bone health. Clinicians should consider relative contraindications to estrogen therapy that may affect treatment decisions, including history of breast cancer, venous thromboembolism, cardiovascular or cerebrovascular disease.

Data derived largely from convenience samples29 suggest that transgender women receiving hormone therapy may be at higher risk of deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction30,31 compared to rates expected among cisgender people. It is unknown whether these risks are greater than those reported among postmenopausal cisgender women taking exogenous estrogens.

Data from transgender women are insufficient to report associations between thrombosis risk and hormone doses, hormone blood levels, route of administration, or duration of therapy.

However, extrapolation of data from observational studies of postmenopausal cisgender women may support the strategy of reducing estrogen dosage or switching to transdermal estrogen preparations in transgender women of a similar age.32,33

Neither the World Professional Association for Transgender Health (APMST) nor the Endocrinological Society recommends the use of ethinyl estradiol because it appears to be particularly thrombogenic.23,25,34 Treatment generally includes other testosterone-lowering agents that allow lower doses of estrogens. . Estrogenic and antiandrogenic therapies are started together.

The adjuvant agents most frequently used to reduce androgen levels are spironolactone (potassium-sparing diuretic), which blocks the action of androgen at its receptor and decreases testosterone levels35,36; cyproterone acetate (a progestin), which is popular in Europe; and gonadotropin-releasing hormone (GnRH) agonists. Spironolactone is often administered at a higher dose for this indication than for the treatment of hypertension.

Cyproterone acetate can suppress gonadotropins and acts as an androgen receptor antagonist. GnRH agonists suppress testosterone levels but are generally considered second-line therapy due to their high cost. While other progestins (e.g., medroxyprogesterone acetate and micronized progesterone) can suppress gonadotropins and therefore testosterone secretion, they are not recommended by the Endocrine Society.

Medroxyprogesterone acetate has been associated with an increased risk of heart disease and breast cancer in postmenopausal women taking conjugated estrogens,33 and there is concern that the risk may extend to other progestins. Although finasteride, a 5-alpha-reductase 2 inhibitor, inhibits the conversion of testosterone to a more potent dihydrotestosterone in some tissues (e.g., prostate and scalp), it is not considered useful if testosterone levels are already at the female rank.

One concern reported with hormone therapy in transgender women is increased prolactin levels (and the potential for the development of a prolactinoma).

Therefore, monitoring of prolactin levels is recommended.25 However, reports of elevation of prolactin levels are limited to clinics using estrogen-cyproterone regimens. Findings from a retrospective study of 98 patients receiving an estrogen-spironolactone regimen showed no cases of elevated prolactin levels in up to 6 years of follow-up.37

> Transmasculine hormone therapy (female to male)

A conventional goal in transmasculine hormone therapy is to provoke physical changes that match gender identity through the administration of testosterone,38 raising hormone levels to the male physiological range (300 to 1000 ng per deciliter).

After approximately 3 to 6 months of treatment, transgender men can anticipate the cessation of menses, the development of a deeper voice, and increased facial and body hair, muscle mass, and sexual desire. Acne may develop or worsen temporarily and should be treated if it bothers. Other changes may occur over longer periods of time, such as the development of a male hair pattern and the enlargement of the clitoris.

Regimens include patches, gels, and testosterone esters . Injectable testosterone esters are increasingly administered subcutaneously rather than intramuscularly because therapeutic levels can be achieved with greater patient comfort.39 The use of skin patches may be limited by the associated pruritic reactions.

Long-acting testosterone ( testosterone undecanoate) is available, but concerns about risks related to pulmonary oil microembolism and anaphylaxis have prompted the need for a risk assessment and mitigation strategy for its use in the United States.

Oral testosterone patches are also available but are difficult to use. Data are lacking to suggest a relative superiority of testosterone treatment options. Target levels are easier to achieve with parenteral therapy, but transdermal therapy can achieve more uniform levels.

Androgens stimulate erythropoiesis . Exogenous androgens may be associated with polycythemia , particularly in people with other risk factors for elevated hematocrit, such as sleep apnea. Hematocrit should be monitored and, if elevated, possible alternative explanations should be investigated.

Androgen doses can be decreased as long as there are no adverse consequences from the dose reduction, such as the resumption of menstruation. Data from cross-sectional and cohort studies have not shown a consistent pattern of changes in lipid levels or increased risk of cardiovascular disease among transgender men receiving androgen treatment.29,30

Although the guidelines take into account concerns about increased risk of breast or endometrial cancer in association with androgen therapy and suggest that practitioners consider hysterectomy in transmasculine patients to avoid the risk of endometrial cancer,25 there is no data that supports the existence of such risks.29,40

> Monitoring of transfeminine and transmasculine therapies

The Endocrine Society guidelines suggest monitoring hormone levels in transgender patients with each hormone dosage adjustment (approximately every 3 months for the first year).

Once target levels are reached, they should be monitored once or twice a year or when the dose is changed. Clinicians should also ask patients about social interactions with family, friends, and coworkers to help determine the need for mental health support.

Transgender-specific data is lacking regarding monitoring of preventive health measures. Clinicians should follow strategies for cisgender people.

Transgender patients should undergo bone mineral density testing if they have had prolonged periods of hypogonadism or if they have other risk factors for osteoporotic fractures that would warrant such investigation in the general population.41,42 Similarly, screening for routine for cancer in the tissues and organs present in accordance with the guidelines established for the general population.25

> Fertility

Transgender-specific hormone therapy may reduce fertility. Genital reconstruction surgery that includes removal of gonads can destroy reproductive potential completely. Before beginning any treatment, patients should be encouraged to consider fertility preservation.43 Transgender women may consider sperm cryopreservation44 and transgender men may consider oocyte or embryo cryopreservation.

Embryo preservation is a more established procedure,43,44 but the costs of oocyte and embryo cryopreservation are high. Oocyte harvesting has been performed on transgender men who have intact ovaries while continuing testosterone treatment. Management is more complicated with transgender children, who may have doubts about their future interest in fertility and may not have developed gametes that are suitable for storage.

> Medical treatment of transgender youth

Although a detailed discussion of transgender youth is beyond the scope of this review, the following recommendations should be considered. Children presenting for evaluation of transgender identity should also be evaluated for existing mood disorders; the risk of suicide is higher in these children than in their cisgender peers.45

The timing of social transition (gender presentation in public) should be discussed. Medical intervention is not indicated before puberty because estrogen and testosterone levels are not noticeable until then. At Tanner stage 2 (onset of puberty) reversible puberty blockers, such as GnRH agonists, can be used.

Under the care of a multidisciplinary team, youth with well-established gender identity that is incongruent with their sex recorded at birth can begin hormone therapy. Adolescents presenting after puberty can be treated with sex steroid hormones, with doses titrated to adult levels.

> Specific surgical options for transgender people

Among medically treated transgender people, surveys suggest that approximately half seek transgender-specific surgical procedures, although these data are limited by the possibility of selection bias.27,46

Plans can change over time, so professionals should review options with transgender patients periodically. Although hormone therapy is not a necessary prerequisite for surgery, for those patients who receive it, the APMST and Endocrine Society guidelines recommend postponing surgical procedures other than transmasculine chest surgery until transgender people have completed at least 1 year of hormonal treatment.23,25 Surgical options are reviewed in Table 2.

The long-term consequences of hormone therapy in transgender people and the best strategy for monitoring remain unclear. Studies comparing the effects of different medical regimens and defining strategies for monitoring patients are lacking.

For example, measuring estradiol alone in transgender women does not reflect the levels of other estrogens that may be present (e.g., estrone produced by the liver after oral ingestion of estradiol). Some people choose lower hormonal doses (for example, because they identify as non-binary); It is unknown whether lower doses are associated with bone loss.

Both the Endocrine Society and APMST provide guidelines for the health care of transgender people.23,25 Current recommendations are generally consistent with these guidelines, with some distinctions.

While the Endocrine Society’s revised guidance no longer requires mental health professionals to determine gender identity in adults, the guideline still expresses a preference for the involvement of these professionals in making that assessment; In the absence of more data, the authors of this review do not express such a preference for adults unless there is evidence of mental health problems.

The Endocrine Society guideline also recommends monitoring prolactin levels in transgender women and considering hysterectomy in transgender men as cancer prophylaxis. However, new data suggest that these procedures may not be necessary.27,37,42

The patient described in the vignette is a transgender man interested in hormone therapy. After establishing that gender identity has been persistent and that the patient is competent to make medical decisions, the practitioner should review the patient’s expectations regarding hormone therapy, as well as the patient’s interest in fertility and surgery. .

Screening by the physician or mental health consultant for mental health conditions that may confound gender identity assessment or complicate patient management should be ensured. The expected benefits and potential risks of hormone therapy should then be reviewed with the patient along with a timeline of when changes can be expected.

The review authors typically begin with weekly subcutaneous self-administration of 50 mg of a testosterone ester after the patient has received training in the clinic.

Usual goals for dosage adjustment include ending menses while maintaining the testosterone level in the normal range, maintaining hematocrit below 50%, and treating acne, if indicated. Additionally, if the patient expresses interest, specific surgical procedures and their challenges can be discussed. Surgery to remove reproductive organs should take place only after the patient has considered the implications for her fertility.

Table 1. Definitions

Table 2. Surgical options for transgender patients.