Oral Micronized Progesterone 200 mg Nightly for Endometrial Protection
Yes, oral micronized progesterone 200 mg taken nightly for 12-14 consecutive days per 28-day cycle provides proven endometrial protection in women with an intact uterus on hormone replacement therapy. 1
Evidence-Based Dosing Regimen
The FDA-approved regimen demonstrates clear efficacy:
Oral micronized progesterone 200 mg daily for 12-14 days per 28-day cycle combined with conjugated estrogens 0.625 mg daily reduced endometrial hyperplasia to 6% compared to 64% with estrogen alone over 36 months of treatment 1
This sequential dosing schedule (12-14 days of progesterone per month) is the minimum duration required for adequate endometrial protection—shorter durations provide insufficient protection 2
Bedtime administration is specifically recommended because progesterone causes mild, transient drowsiness that is minimized when taken at night 3, 4
Why This Regimen Works
The nightly dosing pattern addresses both efficacy and tolerability:
Peak plasma progesterone concentrations occur 2 hours after oral administration, reaching 47.7 nmol/L after a 200 mg dose 5
The biologically active metabolite 20α-dihydroprogesterone remains elevated at approximately 20 nmol/L for at least 12 hours after administration, providing sustained progestational effects on the endometrium 5
Administering the dose at bedtime allows patients to sleep through the peak drowsiness period, which is the only specific side effect of oral micronized progesterone 3, 4
Pairing with Estrogen
When prescribing progesterone for endometrial protection, the estrogen component matters:
Transdermal 17β-estradiol 50-100 μg daily is the preferred estrogen to pair with oral micronized progesterone 200 mg nightly for 12-14 days per month 6, 2
Transdermal delivery avoids first-pass hepatic metabolism, resulting in lower cardiovascular and thrombotic risk compared to oral estrogen formulations 6, 2
Oral 17β-estradiol 1-2 mg daily is an acceptable alternative if transdermal delivery is not feasible 2
Expected Bleeding Pattern
Withdrawal bleeding occurs after each 12-14 day progesterone cycle, typically within 7 days of the last progesterone dose 7, 1
This predictable bleeding pattern is a normal consequence of sequential dosing and should be explained to patients before starting therapy 7
Critical Pitfall to Avoid
Never prescribe progesterone for fewer than 12 days per cycle—this provides inadequate endometrial protection and increases the risk of endometrial hyperplasia 2. The 12-14 day duration is not negotiable; it is based on the minimum exposure needed to induce complete secretory transformation of estrogen-primed endometrium 1, 3.
Alternative Formulations
If oral micronized progesterone is not tolerated:
Vaginal micronized progesterone 200 mg daily for 12-14 days per month provides equivalent endometrial protection with potentially fewer systemic side effects 2, 7
Medroxyprogesterone acetate 10 mg daily for 12-14 days per month is a third-line option, though it has less favorable cardiovascular and metabolic effects compared to micronized progesterone 2, 3
Monitoring
Perform annual clinical review focusing on bleeding patterns, symptom control, and compliance 2
No routine laboratory monitoring is required unless specific symptoms arise 2
Consider baseline transvaginal ultrasound to document endometrial thickness before initiating therapy 7
Safety Profile
Oral micronized progesterone has the most favorable safety profile among progestogen options:
Lowest thrombotic risk among all progestogen formulations 2
Neutral or beneficial effects on blood pressure and cardiovascular endothelial function 2, 8
Does not cause depression and improves deep sleep quality when taken at bedtime 4, 8
Lower breast cancer risk compared to synthetic progestins, based on the E3N cohort study of over 80,000 menopausal women 8