What is the recommended hormone management regimen for a transgender female who is a biological male?

Hormone Management for Transgender Female (Biological Male)

The recommended hormone management regimen for transgender females includes transdermal 17β-estradiol (50-100 μg/24 hours) as first-line therapy, combined with an antiandrogen such as spironolactone to achieve testosterone levels <50 ng/dL. 1, 2

Estrogen Therapy Options

First-Line Approach: Transdermal Estrogen

• Transdermal 17β-estradiol patches releasing 50-100 μg/24 hours are preferred due to lower cardiovascular risk compared to oral formulations 1, 2
• Patches are typically changed twice weekly or weekly depending on the specific brand 1
• Transdermal administration avoids first-pass hepatic metabolism, reducing thrombotic risk 1
• Recent research demonstrates that transdermal estradiol results in more rapid testosterone suppression compared to sublingual options 2

Alternative Estrogen Options

• Oral 17β-estradiol at doses of 1-2 mg daily if transdermal administration is contraindicated or refused 1, 3
• Avoid ethinyl estradiol due to increased risk of venous thromboembolism 4, 5
• Vaginal gel (0.5-1 mg daily) is another option for estrogen delivery 1

Antiandrogen Options

First-Line Antiandrogen

• Spironolactone is commonly used in the United States to suppress testosterone production 1, 2
• Target dose typically 100-300 mg daily, divided into once or twice daily dosing 1

Alternative Antiandrogens

• Cyproterone acetate (not available in US) is effective but carries potential health risks 1, 3
• GnRH agonists are highly effective but more expensive 1, 5
• Bicalutamide is sometimes used but has less evidence supporting its use 1

Monitoring and Targets

Laboratory Monitoring

• Measure trough testosterone levels with target <50 ng/dL (female range) 1, 2
• Monitor estradiol levels; traditional target range of 100-200 pg/mL, though recent evidence questions this specific range 1, 6
• Regular monitoring of liver function, lipid profile, and hemoglobin/hematocrit 1

Expected Physical Changes

• Breast development (variable, typically reaches maximum after 2-3 years) 1
• Decreased lean body mass (3-5% reduction) and increased body fat 1
• Decreased facial/body hair growth 1
• Feminized body shape/composition 1

Risks and Considerations

Cardiovascular Risk

• Increased risk of venous thromboembolism, especially with oral estrogen formulations 1
• Risk increases with age and is higher with ethinyl estradiol 1, 4
• Potential for unfavorable lipid profiles and increased cardiovascular mortality 1

Other Health Considerations

• Potential decrease in libido and sexual function 1
• Decreased fertility and sperm production 1
• Consider fertility preservation options before initiating hormone therapy 1

Adjunctive Therapies

Progesterone

• Current evidence does not strongly support routine use of progesterone 1
• Some patients report improved breast development, but evidence is limited 1
• May increase risk of breast cancer, thromboembolism, and stroke 1

Treatment Algorithm

1. Initial Assessment:

   • Confirm gender dysphoria diagnosis and readiness for hormone therapy 1
   • Screen for contraindications (history of estrogen-sensitive cancers, uncontrolled cardiovascular disease) 1

2. Starting Regimen:

   • Begin transdermal 17β-estradiol patch (50 μg/24 hours) 1, 2
   • Start spironolactone 50-100 mg daily, divided into 1-2 doses 1

3. Dose Titration:

   • Check testosterone and estradiol levels after 1-3 months 1, 2
   • Increase estradiol dose if testosterone remains >50 ng/dL 1, 2
   • Increase spironolactone dose up to 300 mg daily if needed 1

4. Maintenance:

   • Continue monitoring hormone levels every 3-6 months during first year, then annually 1
   • Adjust doses based on clinical response and laboratory values 1, 2

5. Long-term Follow-up:

   • Annual physical examination and laboratory monitoring 1
   • Consider appropriate cancer screening based on anatomy present 1