What is Gender-Affirming Hormone Therapy?

Gender-affirming hormone therapy (GAHT) for transgender women (assigned male at birth, identifies as female) uses feminizing hormones—estrogen and anti-androgens—to align physical characteristics with gender identity. The goal is to induce female secondary sexual characteristics and suppress male features.

Expected Physical Changes:

Changes that WILL occur:

• Breast Development: Begins 3-6 months; maximal at 2-3 years (typically Tanner Stage 2-3; unlikely to reach cisgender female average)
• Decreased Libido and Spontaneous Erections
• Decreased Testicular Volume and Sperm Production (often leads to infertility)
• Softer Skin, Decreased Oiliness
• Body Fat Redistribution: Hips, thighs, face (more feminine contour)
• Decreased Muscle Mass and Strength
• Slowed/Reduced Body and Facial Hair Growth (but won't eliminate existing hair)

Changes that WILL NOT occur with hormones alone:

• Voice: Will NOT become higher (voice training or surgery needed)
• Facial Hair: Existing facial hair will NOT disappear (laser/electrolysis needed)
• Bone Structure: No change to height, hand/foot size, or facial bone structure (changes before puberty only if puberty blockers used)
• Male Pattern Baldness: May slow but won't reverse; hair transplant may be needed

Hormone Regimens:

1. Estrogen (Primary Feminizing Agent):

• 17-beta Estradiol (preferred):
  • Oral: 2-6 mg/day
  • Transdermal (patch): 0.1-0.4 mg twice weekly
  • Injectable (estradiol valerate or cypionate): 5-20 mg IM every 1-2 weeks
• Goal Estradiol Level: 100-200 pg/mL (premenopausal female range)
• Avoid: Ethinyl estradiol (synthetic estrogen in birth control)—higher risk of blood clots

2. Anti-Androgens (Testosterone Suppression):

• Spironolactone: 100-200 mg/day (most common in US)
  • Blocks androgen receptors
  • Monitor potassium (can increase)
• Cyproterone Acetate: 10-50 mg/day (used in Europe/Canada; not FDA-approved in US)
  • Progestogenic anti-androgen
  • Monitor liver function
• GnRH Agonists (Leuprolide, Goserelin): Potent suppressors; expensive; used if other methods inadequate or orchiectomy not desired
• 5-Alpha Reductase Inhibitors (Finasteride, Dutasteride): Can reduce DHT (helps with hair loss); adjunctive therapy

After Orchiectomy (Testicle Removal):

• Anti-androgens can be discontinued
• Estrogen dose may be reduced (testosterone production is eliminated)

Timeline of Effects:

• 1-3 months: Decreased libido, softer skin, initial breast budding
• 3-6 months: Breast growth, decreased muscle mass, body hair thinning
• 6-12 months: Continued breast development, fat redistribution
• 2-3 years: Maximum breast development (may be less than cisgender women)
• Infertility: Often occurs within months; consider fertility preservation BEFORE starting

Risks and Side Effects:

• Venous Thromboembolism (Blood Clots): Increased risk, especially with oral estrogen, smoking, age >40
• Cardiovascular Disease: Small increased risk
• Hyperprolactinemia: Can cause benign pituitary enlargement (prolactinoma rare)
• Infertility (often permanent)
• Liver Dysfunction: Rare; monitor with cyproterone
• Hypertension, Hyperkalemia: With spironolactone
• Mood Changes, Depression
• Weight Gain

Pre-Treatment Evaluation:

• Mental health assessment (gender dysphoria diagnosis, informed consent)
• Medical history and physical exam
• Baseline labs: Testosterone, estradiol, prolactin, lipids, glucose, liver function, kidney function, potassium
• Fertility counseling and preservation options

Monitoring:

• First Year: Labs every 3 months (testosterone, estradiol, prolactin, potassium, liver function)
• After Stable: Labs every 6-12 months
• Monitor for blood pressure, weight, mood
• Goal: Testosterone <50 ng/dL, Estradiol 100-200 pg/mL

Long-Term Health:

• Bone Health: Maintain adequate estrogen to prevent osteoporosis; DEXA scan if risk factors
• Cardiovascular Screening: Monitor cholesterol, blood pressure, diabetes risk
• Breast Cancer Screening: Risk similar to cisgender women; follow mammogram guidelines starting age 50 (or earlier if family history)
• Prostate Cancer Screening: Still required; risk reduced but not eliminated

Fertility Preservation:

CRITICAL: Hormone therapy often causes permanent infertility. Discuss options BEFORE starting:

• Sperm Banking: Cryopreservation of sperm
• Testicular Tissue Cryopreservation: Experimental