Progestin Timing in the Menstrual Cycle for Perimenopausal Women
For perimenopausal women with an intact uterus requiring endometrial protection, progestin should be administered for 12-14 consecutive days each month in a sequential regimen, typically during the latter half of the cycle (analogous to days 15-28 or days 17-28). 1, 2
Sequential Regimen Timing
The standard approach involves continuous estrogen administration throughout the month with progestin added for 12-14 days per 28-day cycle. 1 This mimics the natural luteal phase duration and provides adequate endometrial protection. 3
Specific Dosing Schedules
- Medroxyprogesterone acetate (MPA): 10 mg daily for 12-14 days every 28 days 1, 2
- Micronized progesterone: 200 mg daily for 12-14 days per month (preferred first-line option due to superior cardiovascular and thrombotic safety profile) 1, 2
- Dydrogesterone: 10 mg daily for 12-14 days per month 1
Critical Duration Requirements
Progestin exposure must be at least 12 days per cycle—shorter durations are unsafe. 3, 4 The duration of progestin administration is more important than the dose for endometrial protection. 5
- Progestin use <10 days per cycle carries a relative risk of 1.8 for endometrial cancer 5
- Sequential regimens with ≥10 days of progestin per cycle decrease endometrial cancer incidence to that of non-users 5
- The 12-14 day duration requirement is based on the natural luteal phase length needed for adequate endometrial protection 1, 3
Alternative: Continuous Combined Regimen
For women who prefer to avoid withdrawal bleeding, continuous daily progestin administration is an alternative. 1 This involves:
- MPA 2.5 mg daily continuously 2
- Dydrogesterone 5 mg daily continuously 2
- Norethisterone 1 mg daily continuously 1
Continuous combined regimens provide the most effective endometrial protection. 4
Administration Timing Within the Day
Progesterone capsules should be taken at bedtime as a single daily dose 6 because some women experience extreme dizziness, drowsiness, blurred vision, difficulty speaking, or difficulty walking after taking progesterone. 6
Common Pitfalls to Avoid
- Never use progestin for less than 12 days per cycle in sequential regimens—this significantly increases endometrial hyperplasia and cancer risk 3, 5
- Do not confuse sequential timing with the Standard Days Method (days 8-19 for fertility awareness), which is unrelated to hormone replacement therapy 7
- Shorter durations and lower doses are associated with increased breakthrough bleeding, endometrial hyperplasia, and endometrial cancer 3
Monitoring
Clinical review should occur after 3 months to assess symptom improvement, side effects, and compliance, with annual reviews thereafter. 1, 2 No routine laboratory monitoring is required unless prompted by specific symptoms. 2