Short answer: Both combine an estrogen and a progestin for women with a uterus.12 Climara Pro is a weekly skin patch with estradiol and levonorgestrel. Prempro is a daily tablet with conjugated estrogens and medroxyprogesterone acetate, in four strengths. The WHI risk numbers in both boxed warnings come from daily conjugated estrogens 0.625 mg plus MPA 2.5 mg. Neither label compares them.
| Climara Pro | Prempro | |
|---|---|---|
| What is in it | Estradiol 0.045 mg plus levonorgestrel 0.015 mg per day1 | Conjugated estrogens 0.3 to 0.625 mg plus MPA 1.5 to 5 mg2 |
| How used | One patch once weekly, lower abdomen or upper buttock1 | One tablet by mouth once daily2 |
| Approved for | Hot flashes; preventing postmenopausal osteoporosis1 | Hot flashes; vaginal atrophy; preventing postmenopausal osteoporosis2 |
| Endometrial hyperplasia, 1 year | 0 of 102 (0%) vs 17.3% on an estradiol-only patch1 | 2 of 279 (<1%) on 0.625/2.5 vs 20% on Premarin 0.625 mg alone2 |
| Breast pain | 18.9% vs 9.8% on estradiol alone1 | 26% on 0.625/2.5 vs 8% on placebo2 |
| Vaginal bleeding | 36.8% vs 21.6% on estradiol alone1 | 5% on 0.625/2.5 vs 0 on placebo2 |
| Skin reactions | Application site reactions 40.6%1 | Not applicable2 |
| Missed dose | Apply a new patch as soon as possible1 | Take it as soon as possible, unless it is almost time for the next one2 |
| Boxed warning | WARNING: CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, BREAST CANCER, and ENDOMETRIAL CANCER1 | WARNING: CARDIOVASCULAR DISORDERS, BREAST CANCER, ENDOMETRIAL CANCER and PROBABLE DEMENTIA2 |
Both boxed warnings rest on the Women's Health Initiative, which tested daily oral conjugated estrogens 0.625 mg plus MPA 2.5 mg, the ingredients and dose of Prempro 0.625/2.5. In it, stroke was 33 vs 25 and blood clots 35 vs 17 per 10,000 women-years compared with placebo.2 The Climara Pro label says only those oral doses were studied, so the relevance to other doses, routes or products is not known and the risks cannot be definitively excluded.1 The Prempro label says to assume the risks are similar for other doses.
Climara Pro was compared for 1 year with "a continuous estradiol-only transdermal system": endometrial hyperplasia was 0 of 102 vs 19 of 110 (17.3%). Prempro was compared for 1 year with Premarin 0.625 mg alone: 2 of 279 on Prempro 0.625/2.5 vs 57 of 283 (20%).12 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: Climara Pro side effects, Prempro side effects, the Climara Pro and Prempro dosing schedules, the Prempro missed-dose page, how to store Prempro and Prempro vs Activella: how do the two combined HRT tablets differ?.