What are the available estrogen pills for hormone replacement therapy (HRT) and gender affirmation therapy?

Available Estrogen Pills for Hormone Replacement Therapy

For hormone replacement therapy (HRT) and gender affirmation therapy, the primary available estrogen pills include conjugated equine estrogens (0.3-1.25 mg) and oral estradiol (0.5-2 mg), with transdermal estradiol being preferred due to its more favorable risk profile, particularly regarding venous thrombosis. 1

Available Oral Estrogen Formulations

Conjugated Equine Estrogens (Premarin)

• Available in multiple strengths: 0.3 mg, 0.45 mg, 0.625 mg, 0.9 mg, and 1.25 mg tablets 2
• Derived from pregnant mares' urine
• Contains a mixture of sodium estrone sulfate and sodium equilin sulfate

Oral Estradiol

• Available in three strengths: 0.5 mg, 1 mg, and 2 mg tablets 3
• Synthetic estrogen that is bioidentical to human estradiol

Dosing Considerations

For Menopausal HRT

• Initial recommended doses:
  • Conjugated equine estrogen: 0.625 mg/day
  • Oral estradiol: 0.5-1 mg daily 1
• The American College of Obstetricians and Gynecologists recommends using the lowest effective dose for the shortest duration consistent with treatment goals 1

For Gender Affirmation Therapy

• Typically follows a gradual dose escalation approach:
  • Starting dose: 0.5 mg estradiol every other day
  • Intermediate dose: 0.5-1 mg estradiol daily
  • Maintenance dose: 1-2 mg estradiol daily 4

Route of Administration Considerations

While this question focuses on pills, it's important to note that transdermal estradiol (patches) is often preferred over oral formulations due to:

• More favorable risk profile regarding venous thrombosis
• Avoidance of first-pass liver metabolism
• More stable hormone levels 1

Recommended transdermal dosing: 0.025-0.0375 mg/day patch 1

Risk Considerations

When prescribing estrogen pills, be aware of these risks:

• Estrogen plus progestin therapy increases risk of:

  • Breast cancer
  • Stroke (9 more per 10,000 woman-years)
  • Deep venous thrombosis (12 more per 10,000 woman-years)
  • Pulmonary embolism (9 more per 10,000 woman-years) 1

• Estrogen alone increases risk of:

  • Stroke (11 more per 10,000 woman-years)
  • Deep venous thrombosis (7 more per 10,000 woman-years)
  • Gallbladder disease (33 more per 10,000 woman-years) 1

Special Considerations

For Patients with Intact Uterus

• Estrogen must be combined with a progestin (typically medroxyprogesterone acetate 2.5 mg/day) to prevent endometrial hyperplasia 1, 5

For Patients Post-Hysterectomy

• Estrogen-only therapy is appropriate 6

For Younger Patients (Pubertal Induction)

• Lower starting doses with gradual escalation:
  • Initial: 0.5 mg estradiol every other day
  • 12-18 months: 0.5 mg daily
  • 18-24 months: alternating 0.5 mg and 1 mg

  • 24 months: 1 mg daily 4

For Gender Affirmation

• Injectable estrogen has historically been preferred by many transgender individuals, but supply interruptions have occurred 7
• Oral estradiol remains a reliable alternative when injectables are unavailable

Monitoring

• Evaluate estradiol, FSH, LH levels 8-10 weeks after dose adjustment
• Target estradiol levels within normal postmenopausal range for HRT
• Regular reassessment every 3-6 months to evaluate continued need for treatment 1