What is the standard regimen for transgender hormone therapy and recommended lab follow-up?

Transgender Hormone Therapy and Laboratory Follow-Up

The standard regimen for transgender hormone therapy includes gender-affirming hormones tailored to the individual's gender identity, with regular laboratory monitoring at 3-6 months initially and then annually thereafter. 1, 2

Masculinizing Hormone Therapy (Transgender Men)

Standard Regimen

• Testosterone therapy to achieve serum testosterone concentrations in the typical cisgender male reference range 1
• Administration options:
  • Intramuscular or subcutaneous injections (testosterone cypionate or enanthate)
  • Transdermal gels or patches
  • Oral testosterone undecanoate (less commonly used)

Expected Physical Changes

• Voice deepening (irreversible)
• Facial and body hair growth
• Menstrual suppression
• Increased libido
• Clitoral growth
• Increased muscle mass and decreased fat mass 1

Adverse Effects to Monitor

• Polycythemia
• Reduced HDL cholesterol
• Androgenic alopecia
• Acne
• Pelvic pain and genital dryness
• Potential increased risk of myocardial infarction 1

Feminizing Hormone Therapy (Transgender Women)

Standard Regimen

• Estradiol therapy (primary component)

  • Starting dose: 1-2 mg daily oral or equivalent transdermal dose 3, 4
  • Goal: Achieve estradiol levels in cisgender female range while suppressing testosterone to <50 ng/dL 3
  • Recent evidence suggests transdermal estradiol may provide more effective testosterone suppression with lower overall doses compared to sublingual administration 5

• Anti-androgen options (for those who have not had orchiectomy):

  • Spironolactone
  • Cyproterone acetate (not available in some countries)
  • GnRH analogues
  • Bicalutamide
  • Finasteride 1, 2

Expected Physical Changes

• Body composition changes (increased fat, decreased muscle mass)
• Breast growth
• Skin softening
• Decreased body and facial hair
• Decreased libido
• Reduced erectile function
• Decreased testicular size 1

Adverse Effects to Monitor

• Venous thromboembolism risk
• Weight gain
• Potential cardiovascular disease risk
• Potential impact on bone health 1

Laboratory Monitoring Protocol

Baseline Assessment (Before Starting Therapy)

• Complete blood count
• Comprehensive metabolic panel
• Lipid profile
• Hemoglobin A1c or fasting glucose
• Hormone levels (estradiol, testosterone)

Follow-Up Monitoring

Masculinizing Therapy

• Initial follow-up: 3-6 months after starting therapy 3
• Ongoing monitoring: Annual clinical review 3
• Parameters to check:
  • Testosterone levels
  • Complete blood count (monitor for polycythemia)
  • Lipid profile
  • Liver function tests
  • Blood pressure
  • Weight

Feminizing Therapy

• Initial follow-up: 3-6 months after starting therapy 3
• Ongoing monitoring: Annual clinical review 3
• Parameters to check:
  • Estradiol levels
  • Testosterone levels
  • Potassium levels (if on spironolactone)
  • Liver function tests (especially if on cyproterone acetate)
  • Lipid profile
  • Blood pressure
  • Weight

Important Considerations

Dosage Adjustments

• Hormone doses should be titrated based on clinical response and laboratory values
• The optimal estradiol concentration range of 100-200 pg/mL recommended in guidelines lacks strong evidence for optimal feminization outcomes 6
• Injectable estradiol starting doses may need to be lower (≤5 mg weekly) than current guidelines suggest (2-10 mg weekly) to avoid supraphysiologic levels 7

Special Considerations

• For transgender women with intact uterus, progesterone must be added to estrogen therapy to prevent endometrial hyperplasia 3, 4
• Contraindications for hormone therapy include history of breast cancer, active thromboembolic disorders, history of arterial thrombotic disease, undiagnosed vaginal bleeding, and liver problems 3
• Transdermal estradiol may be preferred for hypertensive patients or those with higher thrombosis risk 1

Monitoring Frequency

• No routine laboratory monitoring is required once established on therapy unless prompted by specific symptoms or concerns 1, 3
• Annual clinical review should focus on compliance, symptom control, blood pressure, and weight 3

Pitfalls to Avoid

• Failing to monitor for polycythemia in transgender men on testosterone therapy
• Overlooking potassium levels in transgender women on spironolactone
• Using oral ethinylestradiol (increased thrombosis risk compared to 17β-estradiol) 1
• Neglecting to add progesterone for transgender men with intact uterus 1, 4
• Assuming the guideline range of 100-200 pg/mL estradiol is optimal for all patients 6