Oral Micronized Progesterone Dosing for Menopausal Hormone Therapy
For postmenopausal women with an intact uterus receiving estradiol therapy, the standard dose is oral micronized progesterone 200 mg daily for 12-14 days per 28-day cycle (sequential regimen), taken at bedtime. 1, 2
Standard Sequential Regimen
The FDA-approved dose is 200 mg orally once daily at bedtime for 12 days sequentially per 28-day cycle when combined with conjugated estrogens or estradiol 2
This 200 mg dose for 12-14 days provides proven endometrial protection, reducing hyperplasia rates from 64% (estrogen alone) to 6% (estrogen plus progesterone) over 36 months of treatment 2
The 12-14 day duration is critical—shorter durations provide inadequate endometrial protection and should never be used 1
Micronized progesterone is preferred over synthetic progestins (medroxyprogesterone acetate, norethisterone) due to significantly lower cardiovascular and thrombotic risk 1
Alternative Continuous Regimen
For women who wish to avoid withdrawal bleeding, 100 mg daily continuously (every day without interruption) is an alternative option 1, 3
This continuous low-dose regimen (100 mg for 25 days per month) efficiently protects the endometrium by fully inhibiting mitoses and induces amenorrhea in 91-93% of women 4
The continuous approach may improve long-term compliance by eliminating monthly bleeding episodes 4
Pairing with Estradiol
Progesterone should be paired with transdermal 17β-estradiol 50-100 μg daily as the preferred estrogen formulation due to lower cardiovascular and thrombotic risk compared to oral estrogen 1, 5
Oral 17β-estradiol 1-2 mg daily is an acceptable alternative if transdermal delivery is not feasible 1
Administration Considerations
Take progesterone at bedtime to minimize the mild, transient drowsiness that can occur 2, 3
Some women may experience difficulty swallowing the capsules; these should be taken with a full glass of water while standing 2
Vaginal administration of 200 mg micronized progesterone is an alternative route, though the ELITE trial demonstrated that vaginal progesterone 45 mg/day for 10 days was insufficient for complete endometrial protection 1, 6
Critical Pitfalls to Avoid
Never use progesterone for fewer than 12 days per cycle in sequential regimens—this provides inadequate endometrial protection and increases endometrial hyperplasia risk 1
Do not use vaginal progesterone at doses lower than 200 mg daily, as 45 mg/day for 10 days resulted in progressive endometrial thickening and higher hyperplasia rates 6
Avoid synthetic progestins (medroxyprogesterone acetate 10 mg or dydrogesterone 10 mg) as first-line options, as they carry higher cardiovascular risk than micronized progesterone 1
Monitoring
Annual clinical review focusing on compliance, bleeding patterns, and symptom control is recommended 1
No routine laboratory monitoring is required unless specific symptoms or concerns arise 1
Endometrial biopsy is indicated if breakthrough bleeding occurs or endometrial thickness exceeds expected parameters on ultrasound 2