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
Divigel
Prometrium vs. Divigel Dosage
Prometrium
Divigel
| 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 |
| 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
| 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
| 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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