Short answer: Both are taken by mouth for part of a cycle: to protect the uterine lining in postmenopausal women taking conjugated estrogens, and to bring on a period after secondary amenorrhea.12 Provera (medroxyprogesterone) is 5 or 10 mg daily for 12 to 14 days a month; Prometrium (progesterone) is 200 mg at bedtime for 12 days. Only Provera's label carries a boxed warning.
| Provera | Prometrium | |
|---|---|---|
| Drug and form | Medroxyprogesterone acetate tablets, 2.5, 5 and 10 mg1 | Progesterone capsules, 100 and 200 mg, in peanut oil2 |
| Approved for | Secondary amenorrhea; abnormal uterine bleeding from hormonal imbalance; preventing endometrial hyperplasia with conjugated estrogens 0.625 mg1 | Preventing endometrial hyperplasia with conjugated estrogens; secondary amenorrhea2 |
| With estrogen after menopause | 5 or 10 mg daily for 12 to 14 days in a row each month1 | 200 mg at bedtime for 12 days in a row per 28-day cycle2 |
| Secondary amenorrhea | 5 or 10 mg daily for 5 to 10 days1 | 400 mg at bedtime for 10 days2 |
| Time of day | Not set in the label1 | Bedtime, because it can cause dizziness and drowsiness2 |
| Uterine lining in a 3-year label trial | No hyperplasia (normal lining) in 95% on 10 mg for 12 days plus conjugated estrogens vs 38% on estrogens alone1 | Hyperplasia in 6% with conjugated estrogens vs 64% on estrogens alone2 |
| Peanut allergy | Not listed1 | Not used; capsules contain peanut oil2 |
| Missed dose | No rule in the label1 | No rule in the label2 |
| Boxed warning | WARNING: CARDIOVASCULAR DISORDERS, BREAST CANCER AND PROBABLE DEMENTIA FOR ESTROGEN PLUS PROGESTIN THERAPY1 | None in the current label2 |
Provera's boxed warning comes from the Women's Health Initiative, where daily conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg, the drug in Provera, raised the risk of blood clots, stroke, heart attack and invasive breast cancer, and of probable dementia in women 65 and older.1 The current Prometrium label has no boxed warning section, but its Warnings section reports the same WHI results and says that only that estrogen and medroxyprogesterone combination was studied, so how the findings apply to other estrogen plus progestogen products is not known.2
Provera's label lists side effects for Provera alone without percentages, including bleeding changes, breast tenderness, nausea, depression, dizziness, headache and weight change.1 Prometrium's 3-year trial with conjugated estrogens reported breast tenderness in 27% vs 6% on placebo, depression 19% vs 12% and dizziness 15% vs 9%; a few women had severe dizziness, drowsiness or blurred vision early in treatment.2
Which, if either, fits is for your prescriber. More detail: Provera side effects, Prometrium side effects, the Provera and Prometrium dosing schedules, the Prometrium missed-dose page, the medroxyprogesterone and progesterone guides, and Bijuva vs Prometrium: how do the two progesterone capsules differ?.