Is vaginal micronized bioidentical progesterone 200mg daily, including during menstruation, more effective than cyclic or oral administration in reducing hyperplastic endometrium?

Vaginal Micronized Progesterone 200mg Daily Without Break for Endometrial Hyperplasia

For treating endometrial hyperplasia, vaginal micronized progesterone 200mg daily without break (continuous administration) is NOT the optimal strategy—cyclic administration (12-14 days per month) is the evidence-based approach that provides adequate endometrial protection while allowing for withdrawal bleeding and monitoring. 1, 2, 3

Route of Administration: Vaginal vs Oral

Vaginal administration of micronized progesterone at 200mg daily is effective for treating endometrial hyperplasia, with a 90.5% complete regression rate when given cyclically (days 10-25 of menstrual cycle) 1. The vaginal route offers:

• Direct endometrial delivery with lower systemic absorption 1
• Favorable safety profile, particularly for women with metabolic disorders 1
• Equivalent endometrial protection to oral administration at similar doses 4, 5

Cyclic vs Continuous Administration

The evidence strongly supports CYCLIC rather than continuous administration for endometrial hyperplasia treatment:

• Cyclic regimens (12-14 days per month) provide complete endometrial protection while allowing withdrawal bleeding, which enables monitoring for breakthrough bleeding that could signal inadequate treatment 6, 3
• The landmark PEPI trial demonstrated that cyclic micronized progesterone 200mg daily for 12 days per cycle completely prevented hyperplasia when combined with estrogen, with rates similar to placebo 3
• In premenopausal women with existing hyperplasia, cyclic vaginal progesterone 100mg (days 10-25) achieved 90.5% regression, with most responses occurring within 3 months 1

Optimal Dosing Strategy

For endometrial hyperplasia treatment, the evidence supports:

• 200mg daily is the most effective dose for both simple and complex non-atypical hyperplasia, with a 97.5% remission rate for simple hyperplasia and 92.4% for complex hyperplasia 2
• 100mg daily shows lower efficacy (81.8% for simple, only 60% for complex hyperplasia) 2
• 300mg daily offers no additional benefit over 200mg 2

Continuous Administration Concerns

Administering progesterone continuously without breaks (including during menstruation) deviates from established protocols:

• Guideline recommendations for hormone replacement therapy specify either sequential (cyclic) or continuous combined regimens, but continuous regimens are designed to prevent withdrawal bleeding in postmenopausal women, not to treat existing hyperplasia 6, 3
• The advantage of cyclic administration is early pregnancy recognition in women of reproductive age, as absence of withdrawal bleeding prompts pregnancy testing 6
• Continuous administration prevents the endometrial shedding that allows clinical monitoring of treatment response 1

Recommended Treatment Protocol

For endometrial hyperplasia in premenopausal women:

1. Micronized progesterone 200mg daily, administered vaginally or orally 1, 2
2. Cyclic regimen: Days 10-25 of menstrual cycle (or 12-14 days per 28-day cycle) 1, 6
3. Duration: 3-6 months with endometrial biopsy at 3 months to assess response 1
4. Continue during menstruation: NO—stop to allow withdrawal bleeding 1

Important Caveats

• Simple hyperplasia responds significantly better than complex hyperplasia (97.5% vs 92.4% regression at 200mg dose) 2
• Recurrence rates are low (1.7% at 3 months, 6.1% at 6 months) with cyclic administration 1
• Medroxyprogesterone acetate (MPA) is the only progestin with definitive evidence for inducing secretory endometrium, though micronized progesterone is recommended by ESHRE guidelines for its superior safety profile 6
• For postmenopausal women on estrogen therapy, continuous combined regimens offer better protection than cyclic regimens, but this applies to prevention, not treatment of existing hyperplasia 4

The proposed strategy of 200mg vaginal progesterone daily without break (including during periods) lacks evidence support and removes the clinical benefit of monitoring withdrawal bleeding patterns.