Prometrium Month-by-Month: What to Expect in the First 3 Months

What does the label schedule for the first three months?

Prometrium is oral micronized progesterone in 100 mg and 200 mg capsules [1]. For endometrial protection in a postmenopausal woman with a uterus taking daily conjugated estrogens tablets, the label directs 200 mg at bedtime for 12 days per 28-day cycle; secondary amenorrhea is treated with 400 mg at bedtime for 10 days [1]. Over three 28-day cycles, the endometrial-protection schedule consists of three 12-day courses [1]. The label gives a cycle schedule rather than a week-by-week course. For endometrial protection, its regimen pairs Prometrium with conjugated estrogens tablets, and the label does not describe use with estradiol [1].

The first days: peak levels and the drowsiness warning

Maximum serum concentration is reached within 3 hours of an oral dose [2]. After five daily doses in postmenopausal women, mean peak was 17.3 ng/mL at 100 mg per day and 38.1 ng/mL at 200 mg per day, with standard deviations often exceeding the means [2].

The label says Prometrium 'may cause transient dizziness and drowsiness and should be used with caution when driving a motor vehicle or operating machinery,' and directs a single daily dose at bedtime [1][2]. During initial therapy a few women have had extreme dizziness or drowsiness, blurred vision, slurred speech, difficulty walking, confusion and loss of consciousness [2].

What the reaction tables and trials cover

The label's reaction tables are not broken down month by month. Its 3-year table compares cyclic Prometrium 200 mg plus conjugated estrogens 0.625 mg (178 women) with placebo (174): breast tenderness 27% vs 6%, abdominal bloating 12% vs 5%, dizziness 15% vs 9%, depression 19% vs 12% [2]. The active arm also took estrogen, so these rates cannot be assigned to progesterone alone [2].

In a label trial of 49 estrogen-primed postmenopausal women with secondary amenorrhea, Prometrium 400 mg/day (25 women) versus placebo (24) gave dizziness 24% vs 4% and abdominal cramping 20% vs 13% [2].

A separate 12-week trial randomized 133 healthy women, 1 to 10 years past their final period, to oral micronized progesterone 300 mg at bedtime or placebo. Among the 114 included in the symptom-score analysis (68 progesterone, 46 placebo), vasomotor symptom scores fell by 10.0 points with progesterone versus 4.4 with placebo, an adjusted difference of -4.3 (95% CI -6.6 to -1.9) [5].

What the label says to watch for

The label lists six contraindications, including peanut allergy because the capsules contain peanut oil, known or suspected breast cancer or a history of it, active or past deep vein thrombosis or pulmonary embolism, and known liver disease [1]. The label says Prometrium should be discontinued immediately if a pulmonary embolism, deep vein thrombosis, stroke or heart attack occurs or is suspected, and that progesterone may cause some degree of fluid retention [1][2].

The current Prometrium label, Revision 02/2026, has no boxed warning [1][2]. FDA approved removal of the cardiovascular, breast cancer and probable dementia boxed-warning language from six menopausal hormone products, including Prometrium, on February 12, 2026 [3][4].