Short answer: Both contain conjugated estrogens.12 Prempro adds medroxyprogesterone acetate in the same daily tablet and is for women with a uterus. In the Prempro label's 1-year trial, endometrial hyperplasia was under 1% on Prempro vs 20% on Premarin 0.625 mg alone, counting focal cases. Both carry boxed warnings on endometrial cancer, heart and clot risks, breast cancer and probable dementia.
| Premarin | Prempro | |
|---|---|---|
| What is in it | Conjugated estrogens1 | Conjugated estrogens plus medroxyprogesterone acetate2 |
| Approved for | Hot flashes and vaginal atrophy from menopause; low estrogen from hypogonadism, castration or ovarian failure; palliation of some cancers; osteoporosis prevention1 | For a woman with a uterus: hot flashes and vaginal atrophy from menopause; osteoporosis prevention2 |
| Strengths | 0.3, 0.45, 0.625, 0.9 and 1.25 mg1 | 0.3/1.5, 0.45/1.5, 0.625/2.5 and 0.625/5 mg; Premphase is a 28-day sequence2 |
| Schedule | Daily, or cycles such as 25 days on and 5 off; usual start 0.3 mg1 | One tablet once daily2 |
| Hyperplasia at 1 year, all focal and non-focal | Premarin 0.625 mg alone: 57 of 283 (20%)2 | Prempro 0.625/2.5 mg: 2 of 279 (under 1%)2 |
| Hyperplasia or cancer at 1 year, HOPE study | Premarin 0.625 mg alone: 20 of 249 (8%)2 | Prempro 0.625/2.5 mg: 0 of 2782 |
| Breast pain, first year | 11% on 0.625 mg vs 8% on placebo1 | 26% on 0.625/2.5 mg vs 8% on placebo2 |
| Missed dose | Take as soon as possible; skip if the next dose is near; never 2 at once1 | Take as soon as possible; skip if the next dose is near; never 2 at once2 |
| Boxed warning | WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER and PROBABLE DEMENTIA1 | WARNING: CARDIOVASCULAR DISORDERS, BREAST CANCER, ENDOMETRIAL CANCER and PROBABLE DEMENTIA2 |
In a 1-year trial of 1,376 women, endometrial hyperplasia was under 1% on both Prempro groups and 1% on Premphase, vs 20% on Premarin 0.625 mg alone, or 8% when focal cystic hyperplasia was left out. In the first year of the HOPE study, hyperplasia or cancer was lower on each Prempro dose than on the matching Premarin dose, except at the lowest dose, where each group had 1 case.2 The Premarin label says a progestin should generally be considered for a postmenopausal woman with a uterus.1
Both boxed warnings cover estrogen alone and estrogen plus progestin. In the WHI, conjugated estrogens alone raised the risk of stroke and deep vein clots; with medroxyprogesterone, they also raised the risk of lung clots, heart attack and invasive breast cancer, and both raised probable dementia in women 65 and older.12 Both labels say to use the lowest effective dose for the shortest time that meets treatment goals. Because the breast pain rows come from each label's own table, they are not lined up as a head-to-head comparison.
Which, if either, fits is for your prescriber. More detail: Premarin side effects, Prempro side effects, the Premarin and Prempro dosing schedules, the Premarin and Prempro missed-dose pages, the conjugated estrogens and medroxyprogesterone guides, and Duavee vs Prempro: how do the two menopause tablets differ?.