What is the normal starting dose of progesterone for a postmenopausal woman with no history of thromboembolic events or breast cancer?

Normal Starting Dose of Progesterone for Postmenopausal Women

For a postmenopausal woman with an intact uterus taking estrogen, start with oral micronized progesterone 200 mg at bedtime for 12 consecutive days per 28-day cycle. 1

FDA-Approved Dosing for Endometrial Protection

The FDA-approved regimen for preventing endometrial hyperplasia in postmenopausal women receiving estrogen is:

• Oral micronized progesterone 200 mg as a single daily dose at bedtime
• Duration: 12 consecutive days per 28-day cycle 1
• This dose must be taken with estrogen therapy in women with an intact uterus 1

Alternative Dosing Regimens Based on Clinical Needs

Sequential Regimens (for women desiring withdrawal bleeding):

• Micronized progesterone 200 mg daily for 12-14 days every 28 days when combined with continuous estrogen 2
• Alternative: 100 mg daily for 12-14 days per month for lower-dose estrogen regimens 2
• Higher dose option: 300 mg daily at bedtime for 10 days per month for women willing to accept regular bleeding 3

Continuous Regimens (for women desiring amenorrhea):

• Micronized progesterone 100 mg daily for 25 days per calendar month induces amenorrhea in >90% of women 4
• This lower continuous dose (100 mg/day for 25 days) efficiently protects the endometrium by fully inhibiting mitoses 4

Why Micronized Progesterone is Preferred

Natural micronized progesterone should be the first-choice progestogen rather than synthetic progestins (like medroxyprogesterone acetate) because:

• The WHI trials used medroxyprogesterone acetate (MPA) 2.5 mg daily, which was associated with increased breast cancer risk 5
• A meta-analysis of 86,881 postmenopausal women showed natural progesterone was associated with significantly lower breast cancer risk compared to synthetic progestins 6
• Micronized progesterone has superior cardiovascular and thromboembolism safety profiles compared to synthetic progestins 2
• Synthetic progestins suppress the vasodilating effects of estrogens, while natural progesterone does not 3

Important Administration Details

Timing and Method:

• Always take at bedtime due to potential drowsiness and dizziness 1
• Take with a glass of water while standing if swallowing difficulty occurs 1
• Some women experience transient drowsiness, blurred vision, difficulty speaking, or difficulty walking after initial doses 1

Critical Safety Considerations:

• This product contains peanut oil and is contraindicated in peanut allergy 1
• Do not use in women with unusual vaginal bleeding, current or prior breast/uterine cancer, history of stroke/heart attack, active blood clots, or liver problems 1
• Not indicated during pregnancy or for women without a uterus (hysterectomy) 1

Common Pitfalls to Avoid

Do not confuse different progesterone formulations:

• Injectable 17-alpha-hydroxyprogesterone caproate (17P) 250 mg IM weekly is specifically for preterm birth prevention in pregnant women with prior spontaneous preterm birth, NOT for menopausal hormone therapy 5, 7, 2
• Vaginal progesterone (90-mg gel or 200-mg suppository) is primarily studied for preterm birth prevention and early pregnancy bleeding, not as first-line for menopausal therapy 7, 8

Do not use synthetic progestins as first-line:

• If micronized progesterone is contraindicated or not tolerated, alternatives include medroxyprogesterone acetate 10 mg daily for 12-14 days per month or dydrogesterone 10 mg daily for 12-14 days per month 2
• However, these carry higher cardiovascular and breast cancer risks 2, 6

Monitoring Requirements

• Annual clinical review focusing on compliance 5
• No routine monitoring tests required unless prompted by specific symptoms 5
• Annual pelvic exam, breast exam, and mammogram 1
• Investigate any unusual vaginal bleeding immediately 1

Duration of Therapy

Continue hormone replacement therapy until the average age of natural menopause (45-55 years), then reassess need for continuation 2