Oral Micronized Progesterone Year-1 Outcomes: What Real Users Report

What do participants report after one year?

The best participant-reported data come from controlled trials, chiefly PEPI.

PEPI randomised 875 healthy postmenopausal women aged 45 to 64 to placebo, conjugated equine estrogen 0.625 mg alone, or one of three estrogen-plus-progestin regimens, one of which was conjugated equine estrogen plus cyclic micronized progesterone 200 mg for 12 days a month [4]. At the one-year symptom checklist, every active treatment reduced vasomotor symptoms compared with placebo (odds ratios 0.17 to 0.28), with no added benefit from the progestin, and only progestin-containing regimens were associated with more breast discomfort (odds ratios 1.92 to 2.27). Anxiety, cognitive and affective symptoms did not differ by treatment assignment [1]. The estrogen used was conjugated equine estrogen, not estradiol; the placebo group received no hormones [4].

What the label's trials reported

In the 3-year placebo-controlled trial described in the Prometrium label, adverse reactions were reported for 178 women assigned cyclic Prometrium 200 mg for 12 days per 28-day cycle plus conjugated estrogens 0.625 mg daily, and 174 assigned placebo with no hormones [3]. Over three years: headache 31% vs 27%, breast tenderness 27% vs 6%, depression 19% vs 12%, dizziness 15% vs 9%, abdominal bloating 12% vs 5%, vaginal discharge 10% vs 3%. Hot flashes (11% vs 35%) and night sweats (7% vs 17%) were less frequent than on placebo [3]. These rates cover the full three years rather than year one, and because the active arm also took estrogen, the figures cannot separate progesterone from conjugated estrogens.

Drowsiness, dizziness and contraindications

The label specifies a single daily dose at bedtime [2]. Its patient leaflet says some women become very drowsy or dizzy, and the label says Prometrium may cause transient dizziness and drowsiness and should be used with caution when driving a motor vehicle or operating machinery [2][3]. During initial therapy, a few women have had extreme dizziness or drowsiness with blurred vision, slurred speech, difficulty walking, loss of consciousness, vertigo, confusion, disorientation, feeling drunk and shortness of breath [3]. In the label's small trial of estrogen-primed postmenopausal women with secondary amenorrhea, dizziness was reported by 24% on Prometrium 400 mg/day (n=25) vs 4% on placebo (n=24) [3].

Peanut allergy is a labeled contraindication because the capsules contain peanut oil. The other five are abnormal genital bleeding of unknown cause; known or suspected breast cancer or a history of it; active or prior deep vein thrombosis or pulmonary embolism; active or prior arterial thromboembolic disease such as stroke or myocardial infarction; and known liver dysfunction or disease [2].