What is the recommended protocol for gender affirming hormone therapy?

Gender Affirming Hormone Therapy Protocol

Gender-affirming hormone therapy (GAHT) should be tailored to the individual's gender identity goals, with specific protocols for feminizing and masculinizing treatments that prioritize safety while maximizing desired physical changes. 1, 2

Initial Assessment Requirements

• Confirmed persistence of gender dysphoria or gender incongruence is required before initiating GAHT 3
• Comprehensive baseline assessment should include complete blood count, liver function tests, lipid profile, glucose levels, and baseline hormone levels (estradiol and testosterone) 2
• Fertility preservation counseling must be provided before starting hormone therapy, as both feminizing and masculinizing treatments may affect fertility 2

Feminizing Hormone Therapy Protocol

Core Components

• Estradiol is the cornerstone of feminizing hormone therapy, available in oral, transdermal, or injectable forms 1
• Anti-androgens are typically added to enable lower doses of estrogen while achieving adequate testosterone suppression 1, 2
• Common anti-androgen options include:
  • Spironolactone (most commonly used in many countries) 1
  • Cyproterone acetate 1, 4
  • GnRH agonists 1, 4
  • Bicalutamide 1, 4
  • Finasteride 1, 4

Dosing and Monitoring

• Target testosterone levels should be <50 ng/dL 1
• Target estradiol levels should be in the cisgender female reference range 1
• Monitor hormone levels every 3-6 months during the first year, then annually if stable 1, 2

Expected Physical Changes

• Breast development (variable results) 1
• Decreased muscle mass (3.0-5.5% reduction in lean body mass) 1
• Softening of skin, decreased body/facial hair, decreased libido, and reduced erectile function 2
• Hemoglobin levels decrease to the female reference range 4

Masculinizing Hormone Therapy Protocol

Core Components

• Testosterone therapy is used to induce virilization and suppress feminizing characteristics 2
• Standard doses of testosterone therapy aim to achieve serum testosterone concentrations in the typical cisgender male reference range (300-1,000 ng/dL) 4, 2

Dosing and Monitoring

• Haemoglobin will increase to the male reference range within 3 months 4
• Monitor testosterone levels every 3-6 months during the first year, then annually if stable 2
• Monitor hematocrit regularly, as testosterone therapy can cause erythrocytosis 2, 5

Expected Physical Changes

• Thicker vocal cords producing a deeper voice pitch (irreversible) 4
• Body and facial hair growth (irreversible) 4
• Menstrual suppression 4
• Increased libido and clitoral growth 4
• Increased muscle mass and reduction in fat mass 4, 2

Laboratory Value Interpretation

• For individuals on GAHT for ≥12 months, interpret lab values within reference range for affirmed gender 4
• For individuals on GAHT for <12 months, interpret values in context of type, dose, and duration of GAHT 4
• If GAHT has been stopped for ≥3 months, interpret with reference range for sex assigned at birth 4

Special Considerations for Lab Values

• Red blood cell indices are significantly influenced by GAHT 4
• Liver enzymes are mildly influenced by GAHT 4
• Electrolytes/BUN may fluctuate secondary to spironolactone 4
• Creatinine and creatinine clearance are influenced by GAHT; consider using cystatin C instead 4
• Troponin and PSA should use reference ranges from sex assigned at birth 4

Potential Side Effects and Management

Feminizing Therapy Risks

• Increased risk of venous thromboembolism compared to cisgender individuals 1, 2
• Elevated risk of ischemic stroke and myocardial infarction 1
• Weight gain and potential compromised bone structure 2

Masculinizing Therapy Risks

• Erythrocytosis 2, 5
• Increased blood pressure 5
• Elevated triglycerides and LDL cholesterol, decreased HDL cholesterol 2, 5
• Acne, androgenic alopecia, and pelvic pain 4, 2

Special Populations

Adolescents

• Puberty blockers (GnRH analogues) can be used in early puberty to suppress testosterone and estradiol 4
• Puberty blockers halt development of irreversible secondary sexual characteristics 4
• Feminizing or masculinizing hormone therapy is typically initiated at age 16 years 3
• Puberty blockers have been shown to reduce suicidality and improve psychological function 4

Monitoring Algorithm

1. Baseline assessment before starting therapy 1, 2
2. Check hormone levels at 3 months after initiating therapy 2
3. Monitor every 3-6 months during the first year 1, 2
4. Annual monitoring once stable 1, 2
5. More frequent monitoring for those with pre-existing cardiovascular conditions 2