Prometrium is a prescription progesterone capsule used primarily for two purposes: preventing dangerous thickening of the uterine lining in postmenopausal women taking estrogen, and treating missed periods (secondary amenorrhea). It’s also widely used off-label to support early pregnancy during fertility treatments. Unlike synthetic progestins, Prometrium contains micronized progesterone that is chemically identical to the progesterone your ovaries naturally produce.
Protecting the Uterine Lining During Menopause
The most common use of Prometrium is as part of hormone replacement therapy for postmenopausal women who still have a uterus. When estrogen is taken alone, it stimulates the uterine lining to grow thicker over time, a condition called endometrial hyperplasia. Left unchecked, this overgrowth can become a precursor to uterine cancer. Prometrium counteracts that risk by triggering the lining to shed periodically, much like a natural menstrual cycle does.
The difference is striking. In a clinical trial following 358 postmenopausal women for up to 36 months, 64 percent of women taking estrogen alone developed endometrial hyperplasia. Among women who added Prometrium to their estrogen regimen, that number dropped to just 6 percent. For this use, the typical schedule is one 200 mg capsule taken at bedtime for 12 days out of every 28-day cycle, alongside daily estrogen.
Restarting Missed Periods
Prometrium is also FDA-approved for treating secondary amenorrhea, which is when periods stop for reasons other than pregnancy or menopause. This can happen due to stress, significant weight changes, hormonal imbalances, or conditions like polycystic ovary syndrome. Taking progesterone for a set number of days mimics the natural hormonal shift that triggers the uterine lining to shed, essentially jump-starting a period.
For this use, the typical course is 400 mg taken at bedtime for 10 days. After you stop taking the capsules, the drop in progesterone signals your body to begin a withdrawal bleed, usually within a few days. This approach helps confirm that the uterus is responsive to hormones and can also be part of a broader evaluation of why periods have stopped.
Fertility Support and Early Pregnancy
Although not an FDA-approved indication, Prometrium is one of the most commonly prescribed medications in fertility treatment. After ovulation, progesterone plays a critical role in preparing the uterine lining for a fertilized egg to implant. It makes the endometrium more receptive and helps regulate immune responses that could otherwise interfere with implantation. If progesterone levels are too low during this window, a pregnancy may not take hold even when fertilization occurs.
Fertility clinics frequently prescribe progesterone during the luteal phase (the two weeks between ovulation and a period) for women undergoing procedures like intrauterine insemination or IVF. In a study of over 1,100 insemination cycles, adding progesterone support increased the live birth rate from 14.5 percent to 19.7 percent. Clinical pregnancy rates and ongoing pregnancy rates were also significantly higher, with no difference in miscarriage rates or effects on newborn health.
For fertility uses, progesterone is often given vaginally rather than orally, since the vaginal route delivers more of the hormone directly to the uterus. Some clinicians do prescribe the oral capsules as well, depending on the treatment plan.
Preterm Birth Prevention
Vaginal progesterone is recommended for preventing spontaneous preterm birth in certain high-risk pregnancies. Clinical guidelines support its use for women with a singleton pregnancy and a short cervix (25 mm or less, measured between 16 and 24 weeks), women with a history of spontaneous preterm birth, and women carrying twins who also have a short cervix. The recommended dose in these cases is 200 mg of vaginal micronized progesterone daily. Studies have not linked this use to an increase in birth defects or negative effects on child development.
How Prometrium Differs From Synthetic Progestins
Prometrium is micronized, meaning the progesterone particles are ground extremely fine so your body can absorb them through the digestive tract. The hormone itself is bioidentical, structurally the same molecule your ovaries produce during the second half of each menstrual cycle. This distinguishes it from synthetic progestins like medroxyprogesterone, which have a different chemical structure and a somewhat different side effect profile. Many women and clinicians prefer bioidentical progesterone for hormone therapy because it more closely replicates the body’s natural hormone activity.
Common and Serious Side Effects
The most frequently reported side effects are drowsiness, dizziness, bloating, breast tenderness, headache, mood swings, and nausea. Drowsiness is common enough that Prometrium is specifically recommended to be taken at bedtime. It can also affect coordination and reaction time, so you should know how it affects you before driving or doing anything that requires sharp focus. Some women notice irregular spotting or swelling in their hands, feet, or ankles.
Serious side effects are less common but important to recognize. These include symptoms of blood clots (leg pain, swelling, or warmth, shortness of breath, chest pain), signs of stroke (sudden numbness, trouble speaking, severe headache, vision changes), and indicators of liver injury (upper right abdominal pain, dark urine, yellowing skin or eyes). Worsening depression or new migraines also warrant prompt medical attention. Gum tenderness or minor bleeding is another lesser-known effect to be aware of.
Who Should Not Take Prometrium
One detail that catches many people off guard: Prometrium capsules contain peanut oil as an inactive ingredient. If you have a peanut allergy, you cannot take this medication. This applies to both the 100 mg and 200 mg capsules.
Beyond the peanut allergy concern, Prometrium is contraindicated for women with undiagnosed abnormal vaginal bleeding, a history of or current breast cancer, active or past blood clots in the legs or lungs, a history of stroke or heart attack, known liver disease, or known or suspected pregnancy (for the oral formulation specifically, since vaginal progesterone is used in pregnancy under clinical supervision). These restrictions exist because progesterone can worsen some of these conditions or mask symptoms that need investigation.