Short answer: Both pair conjugated estrogens with a second drug that lowers the risk of endometrial hyperplasia in women with a uterus.12 Duavee adds bazedoxifene, an estrogen agonist/antagonist; Prempro adds the progestin medroxyprogesterone acetate. Both treat moderate to severe hot flashes and help prevent osteoporosis; Prempro also treats vaginal atrophy. Both carry a boxed warning. Neither label reports a trial against the other.
| Duavee | Prempro | |
|---|---|---|
| What it contains | Conjugated estrogens 0.45 mg and bazedoxifene 20 mg; one strength1 | Conjugated estrogens with medroxyprogesterone acetate; four strengths from 0.3 mg/1.5 mg to 0.625 mg/5 mg2 |
| Approved for (women with a uterus) | Moderate to severe hot flashes; preventing postmenopausal osteoporosis1 | Moderate to severe hot flashes; moderate to severe vulvar and vaginal atrophy; preventing postmenopausal osteoporosis2 |
| How taken | One tablet daily, with or without food, swallowed whole; an opened blister pack is used within 60 days1 | One tablet daily; Premphase gives estrogens alone on days 1 to 14 and both drugs on days 15 to 282 |
| Side effects in label trials | Four trials vs placebo: muscle spasms 9% vs 6%, nausea 8% vs 5%, diarrhea 8% vs 5%1 | First year vs placebo: breast pain 26% on 0.625 mg/2.5 mg vs 8%, abdominal pain 11% vs 6%2 |
| Uterine lining | Bazedoxifene lowers the endometrial hyperplasia risk from the estrogen; no progestin is added1 | Hyperplasia under 1% on Prempro at one year vs 20% on conjugated estrogens alone2 |
| Missed dose | Take it when remembered unless the next dose is near; never two at once1 | Take it as soon as possible unless the next dose is near; never two at once2 |
| Boxed warning | Endometrial cancer, cardiovascular disorders and probable dementia1 | Cardiovascular disorders, breast cancer, endometrial cancer and probable dementia2 |
The Prempro box draws on the Women's Health Initiative study of conjugated estrogens plus medroxyprogesterone: more blood clots, stroke, heart attack and invasive breast cancer (41 vs 33 cases per 10,000 women-years), and more probable dementia in women 65 and older.2 The Duavee box draws on the estrogen-alone study and has no breast cancer item; the label says Duavee's own effect on breast cancer risk is unknown, and past or current breast cancer rules it out.1
Women taking Duavee do not also take progestins, extra estrogens or another estrogen agonist/antagonist, and the label does not recommend it over age 75 or with kidney impairment.1 The Prempro label says that when treating only vaginal atrophy, vaginal products should be considered.2 These numbers come from separate trials with different people, lengths and methods, so they are not a head-to-head comparison. Which, if either, fits is for your prescriber. More detail: Duavee side effects, Prempro side effects, the Duavee and Prempro dosing schedules, the Duavee and Prempro missed-dose pages, and Prempro vs Activella: how do the two combined HRT tablets differ?.