Prometrium Seasonal Use Considerations: A Clinical Guide to Micronized Progesterone Year-Round

Does the season change how Prometrium works?

The label's dosing section lists the same regimen for each indication and does not mention season. Prometrium is an oral soft-gelatin capsule, and the label says micronization increases the oral bioavailability of progesterone [2]. The label reports peak serum concentrations within 3 hours, mean peak times of 1.5 hours after 100 mg and 2.3 hours after 200 mg, and dose-proportional levels from 100 to 300 mg per day, with between-person variability so wide that the standard deviation often exceeded the mean [2].

What varies night to night: timing and food

The label directs a single daily dose at bedtime. It says Prometrium may cause transient dizziness and drowsiness and should be used with caution when driving a motor vehicle or operating machinery [1][2]. During initial therapy a few women have had extreme dizziness or drowsiness, blurred vision, slurred speech, difficulty walking, loss of consciousness, vertigo, confusion and shortness of breath [2]. Food is the other documented input: the label says food increased progesterone bioavailability versus fasting at a 200 mg dose, gives no size for that increase, and states that absolute bioavailability is not known [2].

Endometrial protection: what the trials showed

In a label-reported trial of 358 postmenopausal women with a uterus, participants received cyclic Prometrium 200 mg with conjugated estrogens, conjugated estrogens alone, or placebo [1]. Hyperplasia had appeared by 36 months in 6% of the combination group (7 of 117), 64% of the estrogen-only group (74 of 115) and 3% of the placebo group (3 of 116); atypical hyperplasia occurred in 1%, 12% and 0% [1].

In the PEPI trial, 596 women had endometrial biopsies during three years of treatment [4]. The estrogen was conjugated equine estrogen. Every estrogen-plus-progestin arm, including conjugated equine estrogen plus cyclic micronized progesterone 200 mg, had hyperplasia rates similar to placebo (P=.16), while unopposed estrogen raised simple (27.7% vs 0.8%), complex (22.7% vs 0.8%) and atypical (11.8% vs 0%) hyperplasia [4].

Safety items that do not change with the season

Peanut allergy is a labeled contraindication because the capsules contain peanut oil. The other contraindications are abnormal genital bleeding of unknown cause, known, suspected or past breast cancer, active or past deep vein thrombosis or pulmonary embolism, active or past arterial thromboembolic disease, and known liver dysfunction or disease [1]. The label says to discontinue Prometrium immediately if a PE, DVT, stroke or MI occurs or is suspected [2]. Progesterone may cause some fluid retention, and the label says the capsules should not be used during pregnancy [1][2].