What is the recommended dosage of micronized progesterone for a postmenopausal woman with a history of endometriosis as part of a sequential hormone replacement therapy (HRT) regimen?

Micronized Progesterone Dosing for Sequential HRT in Postmenopausal Women with Endometriosis History

For a postmenopausal woman with a history of endometriosis on sequential hormone replacement therapy, the recommended dose is micronized progesterone 200 mg orally at bedtime for 12-14 consecutive days per 28-day cycle, combined with continuous estrogen therapy. 1, 2, 3

Specific Dosing Regimen

The FDA-approved dosing for endometrial protection is micronized progesterone 200 mg taken as a single daily dose at bedtime for 12 days sequentially per 28-day cycle. 3 This regimen provides proven endometrial protection when combined with continuous estrogen therapy in postmenopausal women with an intact uterus. 1, 4

Sequential Regimen Details

• Micronized progesterone 200 mg orally at bedtime for 12-14 days per 28-day cycle is the first-line progestin choice due to its superior cardiovascular and breast safety profile compared to synthetic progestins while maintaining adequate endometrial protection. 1, 2

• The 12-14 day duration is critical—shorter durations provide inadequate endometrial protection against estrogen-induced endometrial hyperplasia. 1, 2, 4

• This dose fully inhibits endometrial mitoses and induces amenorrhea in 91-93% of postmenopausal women, allowing better compliance to long-term therapy. 5

Estrogen Component Pairing

• Pair with transdermal 17β-estradiol 50-100 μg daily (applied continuously via patch changed twice weekly) as this route bypasses hepatic first-pass metabolism and has lower cardiovascular and thrombotic risk compared to oral formulations. 1, 2

• 17β-estradiol is explicitly preferred over ethinylestradiol or conjugated equine estrogens for hormone replacement therapy. 1

Special Considerations for Endometriosis History

For women with endometriosis who required oophorectomy, combined estrogen/progestogen therapy can be effective for treating vasomotor symptoms and may reduce the risk of disease reactivation. 1 The addition of progestogen to estrogen is particularly important in this population to minimize potential reactivation of residual endometriotic tissue. 1

Alternative Dosing Options

If the standard 12-14 day sequential regimen is not tolerated or amenorrhea is strongly preferred:

• Micronized progesterone 100 mg orally at bedtime for 25 days per calendar month (continuous-extended regimen) efficiently protects the endometrium and induces amenorrhea in over 90% of women. 2, 5, 6

• Vaginal micronized progesterone 100 mg every other day for at least 10 days per month may provide endometrial protection for up to 3-5 years (off-label use). 2, 4

Why Micronized Progesterone Over Synthetic Progestins

• Micronized progesterone minimizes hormonal-related cardiovascular risks when compared to synthetic progestogens and has a neutral or beneficial effect on blood pressure. 1

• Micronized progesterone shows one of the best safety profiles in terms of thrombotic risk compared to synthetic progestins. 1

• Micronized progesterone does not increase cell proliferation in breast tissue in postmenopausal women compared with synthetic medroxyprogesterone acetate (MPA). 7

• The ESHRE guidelines include micronized progesterone among recommended progestogens due to its demonstrated safer pharmacological profile, though they note that the strongest evidence of endometrial protection remains for oral cyclical combined treatment. 1

Alternative Progestogen Options (Second-Line)

If micronized progesterone is not tolerated or unavailable:

• Medroxyprogesterone acetate (MPA) 10 mg daily for 12-14 days per month is the only progestin with the most extensive evidence demonstrating full effectiveness in inducing secretory endometrium, though it has less favorable cardiovascular effects. 1, 2

• Dydrogesterone 10 mg daily for 12-14 days per month is listed among suggested progestins by ESHRE guidelines. 1, 2

Administration Guidance

• Take micronized progesterone at bedtime as some women experience drowsiness and/or dizziness after taking it. 3

• In rare cases, symptoms may include blurred vision, difficulty speaking, difficulty with walking, and feeling abnormal—if these occur, discuss with healthcare provider immediately. 3

• If difficulty swallowing capsules occurs, take with a glass of water while in the standing position. 3

• This product contains peanut oil and should not be used if allergic to peanuts. 3

Monitoring Requirements

• Annual clinical review focusing on compliance, bleeding patterns, and symptom control is recommended. 1, 2

• No routine laboratory monitoring (estradiol levels, FSH) is required unless specific symptoms or concerns arise. 1, 2

• See healthcare provider right away if unusual vaginal bleeding occurs while taking micronized progesterone. 3

Duration of Therapy

• Use the lowest effective dose for the shortest duration consistent with treatment goals, with annual reassessment of risks versus benefits. 1, 2

• Oral micronized progesterone provides endometrial protection if applied sequentially for 12-14 days/month at 200 mg/day for up to 5 years. 4

Critical Pitfalls to Avoid

• Never use progesterone for fewer than 12 days per cycle in sequential regimens—this provides inadequate endometrial protection and dramatically increases endometrial cancer risk. 2, 4

• Never prescribe estrogen alone to women with an intact uterus—unopposed estrogen increases endometrial cancer risk 10- to 30-fold if continued for 5 years or more. 1

• Do not assume all progestogens have equivalent safety profiles—synthetic progestins like MPA have been associated with metabolic and vascular side effects that can be minimized or eliminated through use of natural micronized progesterone. 6