What is a safe dose of progesterone (a steroid hormone) for a postmenopausal female?

Safe Progesterone Dosing for Postmenopausal Women in Their Late 50s

For a postmenopausal woman in her late 50s with an intact uterus requiring progesterone for endometrial protection, the safe and recommended dose is oral micronized progesterone 200 mg daily at bedtime for 12-14 days per month in a sequential regimen, or 100 mg daily continuously if amenorrhea is preferred. 1, 2

Primary Dosing Recommendations

Sequential Regimen (Induces Monthly Withdrawal Bleeding)

• Oral micronized progesterone 200 mg daily at bedtime for 12-14 consecutive days per 28-day cycle provides proven endometrial protection when combined with continuous estrogen therapy 1, 3
• This regimen is the first-line choice due to micronized progesterone's superior cardiovascular and thrombotic safety profile compared to synthetic progestins 1
• The 12-14 day duration is critical—shorter durations provide inadequate endometrial protection and should never be used 1

Continuous Combined Regimen (Avoids Withdrawal Bleeding)

• Oral micronized progesterone 100 mg daily continuously without interruption when combined with continuous estrogen for women who prefer amenorrhea 1, 4
• This lower continuous dose (100 mg/day for 25 days per month) efficiently protects the endometrium by fully inhibiting mitoses and induces amenorrhea in over 90% of postmenopausal women 4

Alternative Progestin Options (Second-Line)

If micronized progesterone is unavailable or not tolerated, alternative options include:

• Medroxyprogesterone acetate (MPA) 2.5 mg daily continuously for continuous regimens 1
• MPA 10 mg daily for 12-14 days per month for sequential regimens 1
• Dydrogesterone 5 mg daily continuously or 10 mg daily for 12-14 days per month 1
• Norethisterone 1 mg daily continuously 1

Critical Administration Guidelines

Timing and Route

• Always administer progesterone at bedtime due to common side effects of drowsiness, dizziness, and in rare cases blurred vision or difficulty walking 2
• Take with a full glass of water while standing to prevent swallowing difficulties 2
• Oral route is preferred; vaginal administration (200 mg daily for 10+ days) is an alternative but represents off-label use 1, 3

Estrogen Pairing Requirements

• All women with an intact uterus must receive progesterone when taking estrogen to prevent endometrial hyperplasia and cancer 1, 2
• Pair with transdermal 17β-estradiol 50-100 μg daily as first choice due to lower cardiovascular and thrombotic risk 1, 5
• Oral 17β-estradiol 1-2 mg daily is an acceptable alternative 1

Safety Considerations and Contraindications

Absolute Contraindications

• Peanut allergy (progesterone capsules contain peanut oil) 2
• Current or history of breast cancer or hormone-sensitive malignancies 2
• Active liver disease 5
• Unusual vaginal bleeding of unknown cause 2
• Current or history of blood clots, stroke, or heart attack 2
• Pregnancy 2

Monitoring Requirements

• Annual clinical review focusing on compliance, bleeding patterns, and symptom control 1
• No routine laboratory monitoring required unless specific symptoms arise 1
• Immediate evaluation required for unusual vaginal bleeding, severe headaches, chest pain, leg pain, vision changes, or shortness of breath 2

Evidence-Based Duration Principles

• Use the lowest effective dose for the shortest duration consistent with treatment goals 5
• Risks including venous thromboembolism, coronary heart disease, and stroke occur within the first 1-2 years of therapy 5
• For every 10,000 women taking estrogen-progestin therapy for 1 year, expect 8 additional invasive breast cancers, 9 more strokes, and 12 more deep venous thromboses 5
• Reassess necessity every 3-6 months and attempt to discontinue or taper at regular intervals 5

Common Pitfalls to Avoid

• Never use progesterone for fewer than 12 days per cycle in sequential regimens—this provides inadequate endometrial protection 1
• Never prescribe progesterone alone without estrogen in postmenopausal women—it is used for endometrial protection when estrogen is given 2
• Never start with high doses—evidence shows no additional benefit and increased harm 5
• Never use transdermal progesterone—it does not provide adequate endometrial protection 3

Special Population Considerations

For women with premature ovarian insufficiency in their late 50s (rare but possible if diagnosed earlier), treatment should continue until the average age of natural menopause (45-55 years), though most women in their late 50s would have already reached this threshold 1