What is the typical hormone replacement therapy (HRT) regimen for male-to-female (Mtf) transition?

Male-to-Female (MTF) Hormone Replacement Therapy Regimen

The typical hormone replacement therapy regimen for male-to-female transition consists of estradiol (oral, transdermal, or injectable) combined with an anti-androgen medication (most commonly spironolactone in the US) to suppress testosterone production and induce feminization. 1, 2

Core Medication Components

Estradiol Therapy

• Estradiol is the cornerstone of feminizing hormone therapy, available in multiple formulations 1, 2:
  • Oral estradiol (most common)
  • Transdermal patches or gel
  • Injectable estradiol valerate or cypionate (less commonly used but effective) 2
• Target estradiol levels should be maintained in the cisgender female reference range 1

Anti-Androgen Options

• Spironolactone is the most commonly used anti-androgen in the United States 1, 2
• Alternative anti-androgens include 1:
  • Cyproterone acetate (not available in US)
  • GnRH agonists (directly suppress FSH and LH production at the hypothalamic-pituitary axis) 1
  • Bicalutamide (androgen receptor antagonist)
  • Finasteride (5-alpha reductase inhibitor)
• Anti-androgens enable lower estrogen doses while achieving adequate testosterone suppression 1

Target Hormone Levels

• Testosterone should be suppressed to <50 ng/dL 1
• Estradiol levels should be in the cisgender female reference range 1
• These targets optimize feminization while minimizing adverse effects 1

Expected Physical Changes and Timeline

Early Changes (3-6 months)

• Breast development begins within 3-6 months and continues for 2-3 years 2
• Skin softening and decreased oiliness occur within 3-6 months 2
• Body fat redistribution begins (increases in hips, thighs, face; decreases in abdomen) 2

Ongoing Changes (3-12 months and beyond)

• Decreased muscle mass: 3.0-5.5% reduction in lean body mass, 5% decrease in thigh muscle volume, 4% decrease in quadriceps cross-sectional area 1
• Decreased body and facial hair growth 1
• Hemoglobin levels decrease significantly 1
• Despite muscle changes, transgender women may retain greater muscle cross-sectional area than cisgender women 1

Breast Development Outcomes

• Variable results reported: 1% with cup size <A, 9% with A cup, 16% with B cup, 1% with E cup 1

Critical Monitoring Protocol

Baseline Assessment

• Complete blood count, liver function tests, lipid profile, glucose 1
• Baseline hormone levels (testosterone and estradiol) 1
• Blood pressure assessment 2

Initial Follow-up (3 months)

• Check estradiol and testosterone levels 1
• Adjust doses based on hormone levels and clinical response 1

Ongoing Monitoring

• Every 3-6 months during the first year, then annually if stable 1
• Monitor blood pressure, especially if on spironolactone 2
• Monitor potassium levels in patients on spironolactone 2
• Liver function tests and lipid profiles 2

Cardiovascular and Thrombotic Risks

Transgender women have an increased risk of venous thromboembolism (VTE) compared to cisgender men and women, with elevated risk of ischemic stroke and myocardial infarction. 1

Key Risk Considerations

• The thrombosis risk persists despite changes in estradiol dosing and preparations over time 1
• Avoid ethinyl estradiol, as it may increase VTE risk more than other estrogen formulations 1
• Individualized cardiovascular risk assessment is essential 1
• Potential increased risk of cardiovascular disease compared to cisgender women 2

Additional Clinical Considerations

Bone Health

• Potential decreased bone density with long-term therapy requires monitoring 2
• Inadequate hormone dosing can negatively impact bone density 3

Fertility

• Fertility impairment may become permanent 2
• All patients seeking gender-affirming medical treatment should receive information and counseling for fertility preservation before initiating therapy 4

Cancer Screening

• Breast cancer screening should begin after 5-10 years of estrogen therapy for patients age 40+ 2

Quality of Life Benefits

• Gender-affirming hormone therapy is medically necessary for many transgender individuals, with strong evidence showing improvements in quality of life and relief of psychological distress associated with gender dysphoria 2
• When transgender persons receive medically appropriate care, they have improved mental health, reduction in suicide rates, and lower overall healthcare costs 4

Common Pitfalls to Avoid

• Never use ethinyl estradiol due to increased VTE risk 1
• Ensure adequate testosterone suppression to <50 ng/dL for optimal feminization 1
• Do not neglect potassium monitoring in patients on spironolactone 2
• Avoid inadequate estrogen dosing, which can compromise bone health 3
• Recognize that estrogen therapy may be continued perioperatively in most cases, though individual risk assessment is necessary 2