What is the dosing of transdermal estrogen (Estraderm) and cyclic progesterone (Provera) (medroxyprogesterone acetate) after progesterone therapy fails to induce menstruation?

Dosing of Transdermal Estrogen and Cyclic Progesterone After Progesterone Therapy Failure

For patients who have failed progesterone therapy alone, the recommended dosing is transdermal estradiol patches delivering 50-100 μg daily combined with oral medroxyprogesterone acetate (Provera) 10 mg daily for 12-14 days per month in a sequential regimen. 1, 2, 3

Transdermal Estrogen (Estraderm) Dosing

• Start with transdermal estradiol patches delivering 50 μg daily (to be changed twice weekly or weekly according to specific product instructions) 1
• May increase to 100 μg daily if needed for symptom control 1, 3
• Apply patches to clean, dry, intact skin on the lower abdomen, upper buttocks, back, or upper arms 3
• Transdermal delivery is preferred over oral administration as it:
  • Avoids first-pass hepatic metabolism 1, 3
  • Provides more stable hormone levels 3
  • Has better profile for bone mass accrual 1
  • Has lower risk of venous thromboembolism 3

Cyclic Progesterone (Provera) Dosing

• Medroxyprogesterone acetate (MPA) 10 mg daily for 12-14 days every 28 days 1, 2
• Administer during the last two weeks of each 28-day cycle 1
• This dosing is sufficient for endometrial protection when combined with the recommended estrogen dose 2

Alternative Progesterone Options

• Micronized progesterone 200 mg daily for 12-14 days per month (first choice due to better cardiovascular and thrombotic risk profile) 1, 2
• Dydrogesterone 10 mg daily for 12-14 days per month 2
• Vaginal progesterone 200 mg daily for 12-14 days per month (alternative route with good endometrial protection) 2

Monitoring and Follow-up

• Evaluate treatment effect after 3-6 months 3
• Conduct annual clinical reviews to assess compliance and side effects 2, 3
• No routine laboratory monitoring is required unless prompted by specific symptoms 3

Important Considerations

• If withdrawal bleeding is not desired, consider continuous combined regimens using lower progesterone doses (2.5 mg MPA daily or 5 mg dydrogesterone daily) 1, 2
• For women requiring contraception, consider 17β-estradiol-based combined oral contraceptives 1, 2
• Use the lowest effective dose for the shortest duration consistent with treatment goals 4
• Reevaluate periodically (every 3-6 months) to determine if treatment is still necessary 4

Caution

• Previous studies have shown that transdermal progesterone cream alone may not provide adequate endometrial protection, highlighting the importance of proper oral or vaginal progesterone dosing 5, 6
• Low-dose oral progesterone (100 mg/day) given for 25 days can effectively protect the endometrium and induce amenorrhea in most postmenopausal women 7
• Combined transdermal patches containing both estrogen and progestin are available in some countries and may improve compliance 1, 8