What is the typical hormone replacement therapy regimen for transgender women?

Hormone Replacement Therapy for Transgender Women

For transgender women, the optimal hormone regimen consists of transdermal 17β-estradiol (50-100 μg/24 hours) as first-line therapy combined with spironolactone (100-300 mg daily) to achieve testosterone suppression below 50 ng/dL. 1

Core Treatment Components

Estrogen Therapy

• Transdermal 17β-estradiol patches (50-100 μg/24 hours) are the preferred formulation due to lower cardiovascular and thrombotic risk compared to oral preparations 1, 2
• Transdermal administration avoids hepatic first-pass metabolism, minimizing impact on hemostatic factor synthesis and providing superior safety profiles regarding blood pressure, lipid metabolism, and inflammatory markers 1
• Alternative estrogen delivery includes vaginal gel (0.5-1 mg daily), though transdermal patches remain first-line 1
• Avoid oral ethinyl estradiol preparations due to significantly elevated thrombotic risk 1

Injectable Estradiol Considerations

• If injectable estradiol cypionate or valerate is used, start at ≤5 mg weekly (subcutaneous or intramuscular) rather than the traditional 2-10 mg weekly range 3
• Current guideline-recommended starting doses (2-10 mg weekly or 5-30 mg every 2 weeks) frequently produce supraphysiologic levels across the injection cycle 3
• Titrate based on clinical response and hormone levels rather than using fixed high-dose protocols 3

Anti-Androgen Therapy

• Spironolactone is the standard anti-androgen in the United States, typically dosed 100-300 mg daily in divided doses 1, 2
• Target testosterone suppression to <50 ng/dL (female reference range) 1
• Peripheral androgen receptor antagonists like spironolactone may not necessarily lower testosterone concentrations but effectively block androgen action 2
• Alternative anti-androgens include cyproterone acetate (not available in US), bicalutamide, finasteride, or GnRH analogues 2

Monitoring Protocol

Initial Phase

• Check testosterone and estradiol levels after 1-3 months of therapy initiation 1
• Monitor every 3-6 months during the first year 1
• The traditional target estradiol range of 100-200 pg/mL lacks strong evidence for optimal feminization, though most individuals achieve concentrations in the cisgender female reference range 2, 4

Ongoing Monitoring

• Annual monitoring after stabilization 1
• Regular assessment of liver function, lipid profile, and hemoglobin/hematocrit 1
• Blood pressure monitoring due to cardiovascular risk 1

Expected Physical Changes

Reversible Effects

• Breast development (typically begins within 3-6 months) 2
• Body composition changes with increased fat mass and decreased muscle mass 2
• Skin softening 2
• Decreased body and facial hair 2
• Decreased libido and reduced erectile function 2
• Testicular size reduction 2

Irreversible Male Puberty Characteristics

• Voice pitch remains unchanged (laryngeal prominence persists) 2
• Bone structure does not change 2
• These require surgical intervention if modification is desired 2

Cardiovascular and Thrombotic Risk Management

Risk Profile

• Transgender women have consistently elevated risk of venous thromboembolism compared to both cisgender men and women, even with modern estradiol preparations 2
• Increased risk of ischemic stroke and myocardial infarction relative to cisgender women 2
• Risk persists despite changes in estradiol dosing and preparations over time 2

Risk Mitigation

• Transdermal estradiol significantly reduces thrombotic risk compared to oral formulations 1
• Screen for contraindications including history of estrogen-sensitive cancers and uncontrolled cardiovascular disease 1
• Age increases thrombotic risk; consider this when selecting formulations 1

Progesterone: Not Recommended

Current evidence does not support routine progesterone use due to potential increased risks of breast cancer, thromboembolism, and stroke without clear additional feminizing benefits 1

Perioperative Considerations

• Testosterone suppression therapy (spironolactone) should generally be continued perioperatively 2
• Estradiol therapy continuation versus cessation requires individualized risk-benefit discussion, as routine discontinuation lacks supporting evidence and may cause psychological harm 2
• The physical and mental health benefits of continued estradiol may outweigh thrombotic risk when combined with appropriate thromboprophylaxis 2

Critical Pitfalls to Avoid

• Do not use oral ethinyl estradiol - significantly higher thrombotic risk than transdermal 17β-estradiol 1
• Do not start injectable estradiol at traditional high doses (>5 mg weekly) - leads to supraphysiologic levels 3
• Do not add progesterone routinely - lacks efficacy evidence and increases risks 1
• Do not target specific estradiol levels rigidly - the 100-200 pg/mL range lacks validation for optimal outcomes 4
• Do not discontinue therapy without discussion - hormone therapy improves quality of life and reduces gender dysphoria 2