Maximum Daily Dose of Micronized Progesterone
The maximum daily dose of micronized progesterone studied and used clinically is 400 mg per day, though doses greater than 300 mg per day have not been formally studied in females. 1
Evidence from FDA Drug Label
The FDA label for oral micronized progesterone provides the most authoritative dosing information:
Pharmacokinetic studies in postmenopausal women evaluated doses of 100 mg, 200 mg, and 300 mg daily, showing linear and dose-proportional serum concentrations across this range. 1
In male volunteers, doses up to 400 mg per day were studied and demonstrated linear, dose-proportional pharmacokinetics consistent with those seen in postmenopausal women. 1
The FDA label explicitly states: "Although doses greater than 300 mg per day were not studied in females, serum concentrations from a study in male volunteers appeared linear and dose proportional between 100 mg per day and 400 mg per day." 1
Clinical Context by Indication
For Preterm Birth Prevention (Short Cervix)
- The most studied formulation is 200 mg micronized progesterone capsules administered vaginally daily. 2
- The American College of Obstetricians and Gynecologists recommends 200 mg vaginal micronized progesterone for singleton pregnancies with cervical length ≤20 mm. 2, 3
- An alternative oral dose of 400 mg daily has been suggested, though vaginal administration has stronger evidence. 3
For Hormone Replacement Therapy
- For endometrial protection in postmenopausal women, doses range from 100 mg daily (for 25 days/month) to 300 mg daily (for 10 days/month). 4
- When given for 12-14 days every 28 days with continuous transdermal estradiol, the recommended dose is 200 mg daily (oral or vaginal). 2
- For women desiring amenorrhea, 100 mg daily for 25 days per month effectively protects the endometrium and induces amenorrhea in >90% of women. 5
- For women accepting withdrawal bleeding, 300 mg daily at bedtime for 10 days per month is used. 4
Practical Dosing Considerations
The 300 mg dose should be taken at bedtime to minimize the mild, transient drowsiness that represents the only specific side effect of micronized progesterone. 4
Concomitant food ingestion increases bioavailability of oral micronized progesterone, particularly at the 200 mg dose. 1
There is considerable intersubject variability in absorption, with maximum serum concentrations after a single 300 mg dose ranging from 15.72 to 625.98 ng/mL in postmenopausal women. 6
Important Caveats
Doses above 300 mg daily in females lack formal pharmacokinetic or safety studies, though the 400 mg dose studied in males suggests this would be tolerated. 1
Ketoconazole and other cytochrome P450 3A4 inhibitors may increase progesterone bioavailability, though the clinical relevance is unknown. 1
Micronized progesterone capsules often contain peanut oil in excipients; patients with severe peanut allergies (anaphylaxis) should not receive these formulations and should use vaginal gel formulations instead. 2
The pharmacokinetics have not been studied in patients with hepatic or renal insufficiency. 1