What dose of progesterone (progestin) is recommended for a postmenopausal woman with an intact uterus starting hormone replacement therapy (HRT) with 75mcg of estrogen?

Progesterone Dosing for 75mcg Estrogen HRT

For a postmenopausal woman with an intact uterus taking 75mcg transdermal estrogen, use 200 mg oral micronized progesterone at bedtime for 12-14 consecutive days per 28-day cycle (sequential regimen), or 100 mg daily continuously if amenorrhea is preferred. 1, 2

Primary Recommendation: Micronized Progesterone

Micronized progesterone is the preferred progestogen choice due to its significantly lower cardiovascular and breast cancer risk compared to synthetic progestins. 1, 3

Sequential Regimen (Induces Monthly Withdrawal Bleeding)

• 200 mg oral micronized progesterone at bedtime for 12-14 consecutive days per 28-day cycle 1, 2
• This dose provides proven endometrial protection when paired with any estrogen dose 1, 4
• The 12-14 day duration is critical—shorter durations provide inadequate endometrial protection 1
• Take at bedtime as drowsiness, dizziness, or blurred vision may occur 2

Continuous Combined Regimen (Induces Amenorrhea)

• 100 mg oral micronized progesterone daily without interruption 1, 5
• Induces amenorrhea in 80-93% of women by 3-6 months 5
• Preferred for women who wish to avoid withdrawal bleeding 1
• Studies demonstrate 100 mg daily for 25 days per month fully inhibits endometrial mitoses and prevents hyperplasia 5

Alternative Progestogen Options (Second-Line)

If micronized progesterone is not tolerated or unavailable, consider these FDA-approved alternatives:

Medroxyprogesterone Acetate (MPA)

• Sequential: 10 mg daily for 12-14 days per month 1, 6
• Continuous: 2.5 mg daily without interruption 1, 6
• Extensively studied but less favorable metabolic and cardiovascular profile than micronized progesterone 1, 7

Dydrogesterone

• Sequential: 10 mg daily for 12-14 days per month 1
• Continuous: 5 mg daily without interruption 1
• Lower breast cancer risk than synthetic progestins but higher than micronized progesterone 3

Norethisterone Acetate

• Continuous: 1 mg daily 1
• Higher androgenic activity; reserve for specific indications 1

Critical Dosing Principles

Never use estrogen alone in a woman with an intact uterus—this dramatically increases endometrial cancer risk (RR 2.3). 8, 9

• Unopposed estrogen increases endometrial hyperplasia risk at all doses and durations between 1-3 years 8, 4
• Combined estrogen-progestogen therapy reduces endometrial cancer risk by approximately 90% compared to unopposed estrogen 9, 4
• The progestogen dose and duration must be adequate—inadequate dosing fails to provide endometrial protection 1, 4

Administration and Monitoring

Timing and Administration

• Take micronized progesterone at bedtime with a glass of water while standing to minimize drowsiness and facilitate swallowing 2
• Some women experience extreme dizziness, drowsiness, blurred vision, difficulty speaking, or difficulty walking during initial therapy 2
• If these symptoms occur, discuss with healthcare provider immediately 2

Monitoring Schedule

• Annual clinical review focusing on compliance, bleeding patterns, and symptom control 1, 9
• No routine laboratory monitoring required unless specific symptoms arise 1, 9
• Any unexpected vaginal bleeding requires immediate evaluation with endometrial biopsy 2

Common Pitfalls to Avoid

Do not use progesterone for fewer than 12 days per cycle in sequential regimens—this provides inadequate endometrial protection. 1

• Avoid compounded bioidentical hormones—their safety and efficacy for endometrial protection are unproven 6, 7
• Do not assume all progestogens have equivalent safety profiles—micronized progesterone has the most favorable cardiovascular and breast cancer risk profile 1, 3
• Sequential regimens are preferred over continuous combined for women who can tolerate withdrawal bleeding, as observational data suggest lower breast cancer risk 3

Risk-Benefit Context

For every 10,000 women taking combined estrogen-progestin therapy for 1 year, expect 8 additional invasive breast cancers, 8 more strokes, and 8 more pulmonary emboli, balanced against 6 fewer colorectal cancers and 5 fewer hip fractures. 8, 9 The addition of progestogen does not decrease breast cancer risk but is mandatory for endometrial protection in women with an intact uterus. 8, 3

Contraindications to Progesterone

Absolute contraindications include: 2

• Peanut allergy (micronized progesterone contains peanut oil) 2
• Current or history of breast cancer 2
• Active liver disease 2
• Current or history of venous thromboembolism 2
• Current or history of stroke or heart attack 2
• Unexplained vaginal bleeding 2
• Known or suspected pregnancy 2