What is the approach to managing gender dysphoria in adolescents and adults?

Management of Gender Dysphoria

The cornerstone of managing gender dysphoria is gender affirmation through a combination of psychosocial support, hormone therapy, and potentially surgical interventions, with the primary goal of reducing psychological distress, improving quality of life, and decreasing suicide risk. 1

Foundational Principles

Gender affirmation in a supportive environment directly reduces psychological distress, suicidal ideation, depression, and anxiety while improving overall well-being and quality of life. 1 This is the most critical intervention from a mortality and morbidity standpoint, as transgender and gender-diverse (TGD) persons experience markedly elevated rates of depression, anxiety, and suicide risk compared to cisgender populations. 1

Creating an Affirming Clinical Environment

• Use the patient's chosen name and pronouns consistently - this single intervention reduces psychological distress and suicidal ideation. 1
• Ask patients directly what terms they prefer for forms of address (names, pronouns, relationship terms) and when referring to anatomy (breasts, penis, clitoris, etc.). 1
• Employ trauma-informed practices including explicit permission before physical examination, avoiding approaching from behind (particularly for thyroid exams), and using guided contact where the patient directs the stethoscope placement. 1
• Perform an organ inventory during history-taking to provide medically appropriate care uncoupled from gender presentation. 1

Treatment Algorithm for Adolescents

Pubertal Suppression (Tanner Stage 2 or Higher)

For adolescents who have entered puberty at Tanner Stage G2/B2, initiate GnRH agonists (puberty blockers) to suppress endogenous sex hormone production. 2 These medications directly suppress FSH and LH production by acting on the hypothalamic-pituitary axis, effectively halting testosterone or estrogen production at its source. 3

• This intervention is reversible and provides time for continued psychological assessment while preventing the distress of unwanted pubertal development. 2, 4
• Requires confirmation by a multidisciplinary team including mental health professionals experienced in gender dysphoria assessment. 2, 4

Gender-Affirming Hormone Therapy in Adolescents

Add gender-affirming hormones after the multidisciplinary team confirms persistent gender dysphoria and the patient demonstrates sufficient mental capacity for informed consent to this partially irreversible treatment. 2

• Most adolescents have this capacity by age 16, though compelling reasons may exist to initiate earlier (minimal published experience before age 13.5-14 years). 2
• Treatment requires ongoing collaboration between the prescribing physician and mental health practitioners throughout the transition. 2, 5

Treatment Algorithm for Adults

Pre-Treatment Assessment

Before initiating hormone therapy, complete a comprehensive baseline evaluation: 6, 7

• Complete blood count, liver function tests, lipid profile, glucose 6, 7
• Baseline hormone levels (testosterone, estradiol) 6, 7
• Cardiovascular risk assessment including history of thromboembolism, stroke, myocardial infarction, and baseline blood pressure 6
• Mandatory fertility preservation counseling as hormone therapy may permanently affect fertility 6, 7

Male-to-Female (Transfeminine) Hormone Therapy

Initiate estradiol as the cornerstone medication combined with an anti-androgen to achieve feminization while suppressing testosterone production. 3, 6, 7

Estradiol Dosing Options:

• Oral: 2-6 mg daily 7
• Transdermal: 0.1-0.4 mg/day 7
• Injectable: 5-20 mg IM every 1-2 weeks (estradiol valerate or cypionate) 3, 7

Avoid ethinyl estradiol - it carries significantly higher thrombotic risk than other estrogen formulations. 3, 7

Anti-Androgen Options:

• Spironolactone 100-300 mg daily (most commonly used, typical starting dose 50-200 mg, not the conservative 25 mg) 3, 7
• Cyproterone acetate 3, 7
• GnRH agonists 3, 7
• Bicalutamide 3, 7
• Finasteride 3, 7

Target Hormone Levels:

• Testosterone <50 ng/dL 3, 6, 7
• Estradiol in the cisgender female reference range 3, 6, 7

Expected Physical Changes:

• Breast development (variable: 1% <A cup, 9% A cup, 16% B cup, 1% E cup) 3
• 3.0-5.5% reduction in lean body mass 3, 7
• 5% decrease in thigh muscle volume, 4% decrease in quadriceps cross-sectional area 3
• Skin softening 7
• Decreased body and facial hair 7
• Decreased hemoglobin levels to female reference range 3, 7
• Reduced libido and erectile function 7

Female-to-Male (Transmasculine) Hormone Therapy

Initiate testosterone therapy targeting serum concentrations of 300-1,000 ng/dL in the typical cisgender male reference range. 6

• Monitor for polycythemia/erythrocytosis as a key hematologic complication 6
• Monitor for reduced HDL cholesterol 6
• Monitor blood pressure for potential elevation 6

Monitoring Schedule

Follow this algorithmic monitoring approach: 6, 7

1. Baseline assessment before initiating therapy (labs, medical history, mental health evaluation) 6, 7
2. 3-month follow-up: Check estradiol and testosterone levels, adjust dosing as needed 6, 7
3. Every 3-6 months during first year: Continue hormone level monitoring and dose adjustments 6, 7
4. Annual monitoring once stable: Hormone levels, cardiovascular risk factors, bone health, metabolic indices 6

Critical Safety Considerations

Cardiovascular and Thrombotic Risks in Transfeminine Patients

Transgender women have significantly elevated cardiovascular risks that require vigilant monitoring: 3, 6, 7

• Three-fold increased risk of venous thromboembolism compared to cisgender men and women 3, 7
• Elevated risk of ischemic stroke and myocardial infarction 3, 6, 7
• Risk is dose-dependent and persists despite changes in estradiol preparations 3
• Perioperative thromboprophylaxis is essential - individualized risk assessment required for decisions about continuing or temporarily ceasing estradiol before surgery 3

Spironolactone Monitoring

At typical doses (50-200 mg daily), routine potassium monitoring is unnecessary in young healthy individuals - only 0.75% of young women taking this dose range had potassium levels exceeding 5.0 mmol/L. 3

Consider potassium monitoring if: 3

• Dose increases significantly
• Taking ACE inhibitors, ARBs, NSAIDs, or digoxin
• Older age or renal impairment

Common side effects: Diuresis (29%), menstrual irregularities in transmasculine patients (22%), breast tenderness (17%), breast enlargement, fatigue, headache, dizziness. 3

Addressing Gender-Affirming Practices

Chest Binding (Transmasculine Patients)

Do not recommend against chest binding despite >97% reporting adverse outcomes (back, chest, shoulder pain, dermatologic conditions) - binding significantly reduces anxiety, dysphoria-related depression, and suicidality while improving emotional well-being and confidence. 1

Instead, provide harm reduction strategies: 1

• Only bind when leaving home
• Take "off-days" from binding when possible
• Avoid elastic bandages, duct tape, and plastic wrap
• Practice adequate skin hygiene

Genital Tucking (Transfeminine Patients)

Acknowledge that genital tucking (pushing testicles into inguinal canal, placing scrotum and penis retrograde toward buttocks) provides mental health benefits similar to chest binding despite potential physical risks. 1

Common Pitfalls to Avoid

• Failing to provide comprehensive baseline assessment before initiating therapy 6, 7
• Not monitoring hormone levels regularly, especially during the first year 6, 7
• Overlooking cardiovascular risk factors that may be exacerbated by hormone therapy 3, 6, 7
• Neglecting mental health support during transition 7
• Using ethinyl estradiol instead of safer estrogen formulations 3, 7
• Interpreting lab values based on sex assigned at birth rather than affirmed gender after >1 year of hormone therapy 7
• Making recommendations against chest binding or genital tucking without understanding their critical role in reducing suicidality 1

Surgical Considerations

For gender-affirming surgeries, the treating physician must collaborate with and confirm the criteria for treatment used by the referring mental health practitioner. 2 Surgical removal of natal gonads may be considered when high doses of sex steroids are required to suppress endogenous hormones or in advanced age, allowing reduction of sex steroid treatment. 2

Monitor for reproductive organ cancer risk when surgical removal is incomplete. 2