Prometrium vs. Divigel

See how Prometrium and Divigel compare on approved uses, dosing, side effects, and cost.

Key Takeaways

  • Prometrium is a progesterone capsule used to protect the uterus during estrogen therapy, while Divigel is an estrogen gel used to treat hot flashes.

  • Because Divigel is estrogen without added progesterone, women with a uterus usually need Prometrium or another progestin alongside it.

  • Both carry boxed warnings for cardiovascular disease, dementia, and breast cancer risk, but Prometrium also warns against use in people with a peanut allergy.

Prometrium vs. Divigel Drug Summary

Prometrium

Prometrium is an oral progesterone capsule, chemically identical to the hormone the body makes, used to protect the uterine lining in postmenopausal women taking estrogen and to treat secondary amenorrhea. It's taken once daily at bedtime for a set number of days each cycle, depending on the dose.

Divigel

Divigel is a topical estrogen gel applied once daily to the thigh, used to treat moderate to severe hot flashes associated with menopause. It comes in four strengths so the dose can be adjusted to the lowest amount that controls symptoms.

Prometrium vs. Divigel Side Effects

Prometrium

Most common
Dizziness (up to 16%)
Breast pain (up to 11%)
Headache (up to 10%)
Abdominal pain (up to 10%)

Divigel

Most common
Breast tenderness (>5%)
Metrorrhagia (>5%)
Vaginal mycosis (>5%)
Nasopharyngitis (>5%)

Prometrium vs. Divigel Dosage

Prometrium

Dosage
Dosage Table
STAGE DOSE WHEN
Starting dose 200 mg once daily At the start
Maximum dose 400 mg once daily If needed
Dose changes 1 increase As tolerated

Divigel

Dosage
Dosage Table
STAGE DOSE WHEN
Starting dose 0.25 g once daily At the start
Maximum dose 1.0 g once daily If needed
Dose changes 3 increases As tolerated

Prometrium vs. Divigel Indications

Prometrium

Prometrium is FDA-approved to prevent endometrial hyperplasia in postmenopausal women using estrogen therapy and to treat secondary amenorrhea. Doctors also prescribe it off-label for fertility support, preterm birth prevention, and PMS or PMDD, though these uses aren't FDA-approved.

  • Prevents endometrial hyperplasia with estrogen use

  • Treats secondary amenorrhea

  • Off-label: luteal phase support in IVF

Divigel

Divigel is FDA-approved to treat moderate to severe hot flashes caused by menopause. It's also used off-label for vaginal dryness and as part of gender-affirming hormone therapy, though these aren't its approved indications.

  • Treats moderate to severe hot flashes

  • Off-label: vaginal dryness and atrophy

  • Off-label: gender-affirming hormone therapy

Prometrium vs. Divigel Pros and Cons

Prometrium

Prometrium offers the closest match to the body's own progesterone and is essential for protecting the uterus in women using estrogen therapy. Its capsule form and cyclic dosing schedule require consistent timing, and it isn't suitable for anyone with a peanut allergy.

Pros

  • Bioidentical to the body's natural progesterone

  • Protects the uterine lining during estrogen therapy

  • Also FDA-approved to treat secondary amenorrhea

  • Oral capsule, no skin application required

Cons

  • Contains peanut oil, unsafe for peanut allergy

  • Requires precise cyclic dosing schedule

  • Carries boxed warnings for CV disease and dementia

  • Does not relieve hot flashes on its own

Divigel

Divigel directly targets hot flashes with a flexible, once-daily gel that can be titrated across four doses. Because it's estrogen alone, women with a uterus typically need an added progestin like Prometrium to protect against endometrial cancer.

Pros

  • Four dose strengths allow individualized titration

  • Directly treats moderate to severe hot flashes

  • Topical gel avoids swallowing a daily capsule

  • Absorbed through skin, bypassing the digestive tract

Cons

  • No endometrial protection without added progestin

  • Boxed warning for endometrial cancer risk

  • Risk of secondary exposure to children and pets

  • Requires careful application to avoid transfer

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