Can oral micronized progesterone be given at a dose of 200 mg daily as part of menopausal hormone therapy in postmenopausal women with an intact uterus?

Oral Micronized Progesterone 200 mg Daily for Menopausal Hormone Therapy

Yes, oral micronized progesterone 200 mg daily provides adequate endometrial protection in postmenopausal women with an intact uterus when given for 12-14 days per month in a sequential regimen, and this is the FDA-approved dosing for this indication. 1

FDA-Approved Dosing for Endometrial Protection

The FDA label explicitly states that progesterone capsules should be given as 200 mg orally at bedtime for 12 days sequentially per 28-day cycle to postmenopausal women with a uterus who are receiving daily conjugated estrogens. 1 This is the standard approved regimen for prevention of endometrial hyperplasia. 1

Evidence Supporting 200 mg Daily Dosing

Sequential regimen (12-14 days per month):

• Oral micronized progesterone 200 mg daily for 12-14 days per month provides proven endometrial protection when combined with estradiol, with no cases of endometrial hyperplasia documented in systematic reviews. 2, 3
• This dosing has been validated for up to 5 years of continuous use with maintained endometrial safety. 3
• The 12-14 day duration is critical—shorter durations provide inadequate endometrial protection. 2

Alternative continuous regimen:

• For women preferring amenorrhea, a lower dose of 100 mg daily given continuously (without interruption) also provides adequate endometrial protection. 2, 4
• Continuous dosing at 100 mg daily for 25 days per month achieved 91.6% amenorrhea rates with complete endometrial protection (no hyperplasia found). 4

Optimal Estrogen Pairing

Micronized progesterone should be paired with transdermal 17β-estradiol 50-100 μg daily rather than oral estrogens, as this combination has significantly lower cardiovascular and thrombotic risk. 2 Transdermal delivery avoids first-pass hepatic metabolism, reducing risks of stroke, venous thromboembolism, and coronary events that occur within the first 1-2 years of hormone therapy. 2

Administration Guidelines

• Take at bedtime due to sedative effects—some women experience drowsiness, dizziness, or rarely blurred vision within hours of dosing. 1
• Take with a glass of water while standing if difficulty swallowing occurs. 1
• The medication contains peanut oil and is contraindicated in peanut allergy. 1

Advantages Over Synthetic Progestins

Micronized progesterone is preferred over synthetic progestins (medroxyprogesterone acetate, norethisterone) because:

• Lower cardiovascular risk: Does not suppress the vasodilating effects of estrogens, unlike synthetic progestins. 5
• Lower breast cancer risk: Does not increase breast cancer risk for up to 5 years of use, whereas synthetic progestins show increased risk. 6
• Better metabolic profile: No adverse effects on lipid profiles or glucose metabolism compared to medroxyprogesterone acetate. 7, 5

Critical Monitoring and Safety Considerations

Annual clinical review is required, focusing on:

• Compliance with the regimen 2
• Bleeding patterns (any unscheduled bleeding warrants endometrial evaluation) 1
• Symptom control and tolerability 2
• Reassessment of risks versus benefits 2

No routine laboratory monitoring is needed unless specific symptoms arise. 2

Common Pitfall to Avoid

Never use progesterone for fewer than 12 days per cycle in sequential regimens—this provides inadequate endometrial protection and increases endometrial cancer risk. 2 The minimum duration of 12-14 days mimics the natural luteal phase and is essential for complete secretory transformation of the endometrium. 2

Contraindications

Do not prescribe if the patient has:

• Current or history of breast cancer or hormone-sensitive malignancies 1
• Active liver disease 1
• Unexplained vaginal bleeding (must be evaluated first) 1
• Current or history of blood clots, stroke, or heart attack 1
• Peanut allergy 1

Alternative Dosing Regimens

If the patient cannot tolerate the sequential regimen or prefers amenorrhea:

• Continuous combined: 100 mg daily without interruption provides full endometrial protection long-term. 2, 4
• Vaginal route (off-label): 200 mg micronized progesterone vaginally daily for 12-14 days per month may provide endometrial protection, though this requires closer monitoring with baseline and annual endometrial ultrasound. 2, 3