Transgender Medicine19

GENERAL PRINCIPLES

Care of transgender patients is multifaceted and can include gender-affirming hormone therapy, surgical interventions, and assistance with other ancillary support such as speech therapy, dermatologic therapy, or assistance in navigating legal processes such as for name change.

DIAGNOSIS

• Diagnosis of gender dysphoria is guided by DSM-5 criteria, which includes (1) a marked incongruence between one's experienced/expressed gender and natal gender of at least 6 months in duration and (2) the condition is associated with clinically significant distress due to impairment in social, occupational, or other important areas of functioning. It can be important to involve mental health professionals in situations where patients may be experiencing conditions that have similar features such as body dysmorphic disorder or in situations where abuse or other psychiatric illness such as depression or anxiety may coexist and impact treatment.

• Patients seeking gender-affirming hormone therapy should have persistent, well-documented gender dysphoria/gender incongruence, the capacity to make a fully informed decision and to consent for treatment, and mental health concerns, if present, must be reasonably well controlled.

• The World Professional Association for Transgender Health and Endocrine Society recommends an “informed consent” model for gender-affirming hormone therapy in individuals aged 18 years and older, which does not require a specific mental health evaluation or diagnosis prior to treatment. Informed consent includes a discussion of risks and benefits of gender-affirming hormone therapy, reversible and nonreversible effects, and time course of anticipated changes.

• Individuals should be counseled about options for fertility preservation prior to initiating treatment with gender-affirming hormone therapy.

Clinical Presentation

• Understanding each individual’s journey is important in order to build rapport and trust in the patient­physician relationship. Goals of therapy should be discussed and revisited as they may change over time. Understanding social context is also important such as whether patient has supportive friends and family and whether the patient is presenting as transgender in all private and public situations including the workplace. Knowing these details of a patient’s life can help clinicians offer specific support and keep them attuned to patients’ struggles and challenges.

• A sexual history should be obtained from transgender patients, as with all sexually active patients, in order to screen for high-risk behaviors, assess for sexually transmitted infections, and potentially offer PrEP (pre-exposure prophylaxis for HIV) therapy if desired by the patient.

• Screening for depression and abuse is also paramount.

TREATMENT

Gender-Affirming Hormone Therapy

TRANSGENDER MEN (FEMALE-TO-MALE)

• Testosterone therapy is the mainstay of gender-affirming hormone therapy for transgender men. Testosterone is available in IM or SC injections, transdermal gel preparations, or transdermal patches. Testosterone enanthate or cypionate can be given at a starting does of 50 mg IM or SC weekly or 100 mg IM or SC every 2 weeks. A 21-23 gauge 1” needle is used for IM injection and 25 gauge 5/8” needle is used for SC injection. An autoinjector for SC testosterone is now available for individuals with significant needle phobia. Topical testosterone gel can be applied daily. The starting dose is 50 mg daily. Care should be taken to prevent transfer of the gel to another person. Patches may be started at 2-4 mg daily but may cause skin irritation.

• Testosterone therapy results in increased muscle mass, decreased fat mass, increased facial hair and acne, male pattern baldness in those genetically predisposed, increased sexual desire, clitoromegaly, temporary or permanent decreased fertility, deepening of the voice, cessation of menses, and increased body hair.

• Side effects of testosterone therapy can include erythrocytosis, sleep apnea, hypertension, excessive weight gain, lipid changes, excessive or cystic acne, hypertension, and breast or uterine cancer.

• Adverse events are more likely if testosterone levels are supraphysiologic. Testosterone levels within the normal male range are the goal of therapy.

• Hemoglobin and hematocrit should be monitored in patients on testosterone. Lipid panel should also be measured annually.

TRANSGENDER WOMEN (MALE-TO-FEMALE)

• Estrogen therapy is used to produce secondary sexual characteristics and to suppress testosterone production in transgender women. Oral estradiol, 2-8 mg/d in divided doses, is most often used. Allowing estradiol tablets to dissolve sublingually as opposed to swallowing tablets may improve efficacy and reduce side effect profiles by bypassing first-pass liver metabolism. Transdermal estradiol (typical starting dose of 0.1 mg with uptitration to 0.4 mg) or IM or SC estradiol (starting dose may vary: 2-3 mg weekly or 4-6 mg every other week estradiol valerate, 0.5-1 mg weekly or 1­2 mg estradiol cypionate every other week) can also be prescribed.

• As with testosterone, administration route is guided by patient preference. Estrogen effects include breast tissue development, softening of the skin, and redistribution of adipose tissue. Some patients may also note estrogen alone is insufficient to suppress testosterone levels. A common adjunctive medication is spironolactone, which directly blocks androgen receptor activation. Other adjunctive medications include GnRH agonists and antiandrogenic progestins.

• 5#945;-reductase inhibitors do not reduce testosterone levels and have adverse effects so should not be used.

• Side effects of estrogen therapy include thromboembolic disease, breast cancer, coronary or cerebrovascular disease, cholelithiasis, and hypertriglyceridemia. Thromboembolic risk is high with ethinyl estradiol, which is typically avoided. Individuals are strongly encouraged to avoid tobacco use in order to minimize risk of venous thromboembolism and cardiovascular complications.

• It is important to monitor cardiovascular risk factors by screening for lipid abnormalities and diabetes.

• Clinicians should measure serum estradiol and serum testosterone and maintain them at the level for premenopausal females (100-200 pg/mL and 50 ng/dL, respectively). Creatinine and potassium levels should also be monitored on spironolactone. Prolactin should also be checked annually.

• Treatment should be tailored to patient goals. For example, hormone therapy in transgender females can result in loss of spontaneous erections and this should be discussed as some patients may wish to be able to continue to have erections while other patients do not. Phosphodiesterase-5 inhibitors may be used in transgender women who are experiencing erectile dysfunction.

NONBINARY PATIENTS

• Individuals who identify as genderqueer or nonbinary (do not identify as specifically male or female) may or may not seek gender-affirming hormone therapy or gender-affirming surgery. When they do, they may be seeking different clinical outcomes than their binary transgender peers.

• Doses of gender-affirming hormones may be started at lower doses with goal hormone levels that are lower to try to achieve a more androgynous appearance; however, part of the informed consent process should stress that this goal cannot be guaranteed.

• Additional research is needed to guide care for nonbinary patients and help them meet their specific goals.

MONITORING

Sex steroid hormone levels should be monitored every 3 months during the first year of hormone therapy and then once or twice yearly thereafter.

Gender-Affirming Surgery

• Individuals desiring genital gender-affirming surgery are recommended to have completed at least 1 year of consistent and compliant hormone therapy.

• Transgender males may seek mastectomy, hysterectomy, phalloplasty or metoidioplasty, and/or facial masculinization surgery.

• Transgender females may seek facial feminization, breast augmentation, body feminization surgery which typically includes trunk liposuction and buttocks augmentation, orchiectomy, and vaginoplasty. Typically breast augmentation surgery is delayed until at least 2 years of estrogen therapy as breast tissue can continue to grow during that time.

Other Ancillary Treatments

• Speech therapy can be an important aspect of treatment for transgender individuals as modifying speech patterns can improve patient confidence. Transgender women often work with speech therapists to modulate vocal pitch because this cannot be achieved with estradiol therapy. Transgender men who do not achieve sufficient voice deepening with testosterone may also access these services. Vbcal cord surgery is also an option for patients.

• Transfeminine individuals may also seek laser hair removal or electrolysis as estradiol and antiandrogen therapy alone often does not eliminate terminal hair growth on the face and other areas of the body. Hair removal is part of the preparation process for both transmasculine and transfeminine gender-affirming genital surgeries and may take up to 1 year.

SPECIAL CONSIDERATIONS

• Interpreting labs or bone mineral densities for transgender patients can be challenging as the reference range may be given for patients' assigned sex at birth and not their affirmed gender. Clinicians must always be vigilant to utilize appropriate reference ranges to interpret test results.

• Transgender persons who have undergone gonadectomy may choose not to continue consistent sex steroid treatment after hormonal and surgical sex reassignment, thereby becoming at risk for bone loss.

• Routine care and cancer screening are still necessary for transgender persons with relevant anatomy. Transgender males should continue cervical cancer screening per guidelines. Discussion of prostate cancer screening with transgender women should continue.