Short answer: In the label's 3-year trial of Prometrium 200 mg with conjugated estrogens, side effects more common than on placebo included breast tenderness (27% vs 6%), headache (31% vs 27%), depression (19% vs 12%), dizziness (15% vs 9%), abdominal bloating (12% vs 5%) and vaginal discharge (10% vs 3%). The current label has no boxed warning; it warns about blood clots, stroke and breast cancer with estrogen plus progestin.
What Prometrium is approved for: Prometrium is approved to prevent endometrial hyperplasia (overgrowth of the uterine lining) in postmenopausal women with a uterus who take conjugated estrogens tablets, and to treat secondary amenorrhea, meaning periods that have stopped in women who previously had them (Indications and Usage). The capsules contain peanut oil.
Source
PROMETRIUM (progesterone, USP) Capsules 100 mg and 200 mg, prescribing information and Patient Information. Acertis Pharmaceuticals. DailyMed, version published July 27, 2026. DailyMed setid 1cf237ff-c4f8-4faa-a7aa-77599c856889
No. The current Prometrium label has no boxed warning.
These are the label's own numbers from the Adverse Reactions section. Where the label compares with placebo (a dummy treatment), both columns are shown, so you can see how much more often a reaction happened on Prometrium.
| Adverse reaction | PROMETRIUM 200 mg with Conjugated Estrogens 0.625 mg (n=178) | Placebo (n=174) |
|---|---|---|
| Headache | 31 | 27 |
| Breast Tenderness | 27 | 6 |
| Joint Pain | 20 | 29 |
| Depression | 19 | 12 |
| Dizziness | 15 | 9 |
| Abdominal Bloating | 12 | 5 |
| Hot Flashes | 11 | 35 |
| Urinary Problems | 11 | 9 |
| Abdominal Pain | 10 | 10 |
| Vaginal Discharge | 10 | 3 |
| Nausea / Vomiting | 8 | 7 |
| Worry | 8 | 4 |
| Chest Pain | 7 | 5 |
| Diarrhea | 7 | 4 |
| Night Sweats | 7 | 17 |
| Breast Pain | 6 | 2 |
| Swelling of Hands and Feet | 6 | 9 |
| Vaginal Dryness | 6 | 10 |
| Constipation | 3 | 2 |
| Breast Carcinoma | 2 | <1 |
| Breast Excisional Biopsy | 2 | <1 |
| Cholecystectomy | 2 | <1 |
Postmenopausal women taking cyclic Prometrium 200 mg daily (12 days per calendar month) with conjugated estrogens 0.625 mg, compared with placebo. Note that this compares the combination with placebo, not Prometrium alone. Hot flashes and night sweats were less common on the combination.
| Adverse experience | PROMETRIUM 400 mg (n=25) | Placebo (n=24) |
|---|---|---|
| Fatigue | 8 | 4 |
| Headache | 16 | 8 |
| Dizziness | 24 | 4 |
| Abdominal Distention (Bloating) | 8 | 8 |
| Abdominal Pain (Cramping) | 20 | 13 |
| Diarrhea | 8 | 4 |
| Nausea | 8 | 0 |
| Back Pain | 8 | 8 |
| Musculoskeletal Pain | 12 | 4 |
| Irritability | 8 | 4 |
| Breast Pain | 16 | 8 |
| Infection Viral | 12 | 0 |
| Coughing | 8 | 0 |
A small trial of 49 estrogen-primed postmenopausal women; values are percentage of patients.
During initial therapy, a few women had many or all of: extreme dizziness or drowsiness, blurred vision, slurred speech, difficulty walking, loss of consciousness, vertigo, confusion, disorientation, feeling drunk and shortness of breath.
Over 36 months, endometrial hyperplasia occurred in 6% on conjugated estrogens plus Prometrium 200 mg (cyclical) vs 64% on conjugated estrogens alone and 3% on placebo (Table 3).
WHI estrogen plus progestin trial (oral CE 0.625 mg plus MPA 2.5 mg), women 50 to 79, per 10,000 women-years: stroke 33 vs 24, deep vein thrombosis 25 vs 14, pulmonary embolism 18 vs 9, CHD events 41 vs 35.
WHI invasive breast cancer: relative risk 1.24, 43 vs 35 per 10,000 women-years. A meta-analysis of 24 studies found a relative risk of 2.08 with 5 to 14 years of current estrogen plus progestin use vs never use.
In a 220-woman dosing study of 300 or 400 mg for 10 days per cycle, reactions in 5% or more included nausea, fatigue, vaginal yeast infection, colds, headache, dizziness, breast tenderness, bloating, acne, painful periods, mood swings and urinary tract infection.
The Warnings and Precautions part of the label lists these. Each line gives the label's heading and what it means in plain words.
Who should not take it. People allergic to its ingredients, including peanut allergy (the capsules contain peanut oil), and women with unexplained abnormal genital bleeding, current or past breast cancer, active or past blood clots in the legs or lungs, active or past stroke or heart attack, or known liver problems.
Blood clots, stroke and heart attack. Prometrium is stopped immediately if a blood clot, stroke or heart attack occurs or is suspected, and if feasible 4 to 6 weeks before surgery linked to clots or during long immobilization. WHI found higher risks of these with oral CE plus MPA; whether that applies to other products and routes is not known.
Breast and ovarian cancer. Prometrium is stopped if a hormone-sensitive cancer is diagnosed. Estrogen plus progestin raised invasive breast cancer risk in WHI and increased abnormal mammograms. A meta-analysis linked estrogen plus progestin to ovarian cancer (relative risk 1.37).
Vision problems. Blood clots in the retina have been reported with estrogen. Therapy is stopped pending exam for sudden vision loss, bulging eyes, double vision or migraine, and permanently if retinal lesions are found.
Dizziness and drowsiness. Prometrium may cause short-lived dizziness and drowsiness, so it is taken at bedtime and caution is advised when driving or operating machinery.
Fluid retention. Progesterone may cause some fluid retention, so women with heart or kidney problems are watched carefully.
From the Patient Information that comes with Prometrium:
Dose Track has a side-effect log. Each entry records the symptom, a severity (none, mild, moderate, severe or life-threatening), the date and an optional note, and can be tied to a specific dose or logged on its own. The history screen shows what you logged over time, which makes it easier to tell your prescriber when a reaction started and whether it is easing. The app records what you enter; it does not judge whether a symptom is serious. For anything on the label's call-your-doctor list, call your doctor.
This page is what the FDA label says, in plain words. It is not medical advice. Follow your prescriber, and ask them or your pharmacist about anything here.