Short answer: Both are estrogen creams placed in the vagina with an applicator.12 Premarin Vaginal Cream has conjugated estrogens, 0.625 mg per gram, with schedules of 21 days on and 7 off or twice weekly. Estrace Cream has estradiol, 0.1 mg per gram, started daily and then tapered. Only the Premarin label gives side-effect rates. Neither label compares them. Both carry a boxed warning.
| Premarin Vaginal Cream | Estrace Cream | |
|---|---|---|
| Estrogen | Conjugated estrogens 0.625 mg per gram1 | Estradiol 0.1 mg per gram2 |
| Approved for | Atrophic vaginitis and kraurosis vulvae; moderate to severe painful sex from menopause1 | Moderate to severe vulvar and vaginal atrophy from menopause2 |
| Schedule | 0.5 to 2 g daily for 21 days then 7 off; for painful sex, 0.5 g twice weekly or 21/71 | 2 to 4 g daily for 1 to 2 weeks, then half; maintenance 1 g one to three times a week2 |
| Applicator | Marked in 0.5 g steps up to 2 g1 | Marked at 1, 2, 3 and 4 g2 |
| Tube | 30 g1 | 42.5 g (1 ½ oz)2 |
| Side-effect rates | 12-week trial: breast pain 4.9% (21/7) vs 0% on placebo; headache 3.5% vs 1.4%1 | None given; reactions listed without percentages2 |
| Endometrium | No hyperplasia or cancer in a 52-week study (155 biopsies)1 | No study reported in the label2 |
| Missed dose | No instruction in the label1 | No instruction in the label2 |
| Boxed warning | WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER and PROBABLE DEMENTIA1 | WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER and PROBABLE DEMENTIA2 |
The Premarin Vaginal Cream label reports a 12-week placebo-controlled study of two schedules, 0.5 g daily for 21 days then 7 off, and 0.5 g twice weekly. Superficial vaginal cells rose 28% and 26% vs 3% and 1% on placebo, and vaginal pH fell 1.62 and 1.57 vs 0.36 and 0.26. A 52-week study found no endometrial hyperplasia or cancer.1
The Estrace Cream label is an older format with no clinical studies section and no side-effect percentages. It lists reactions reported with estrogen therapy in general.2
Both labels say some estrogen is absorbed into the body, so the warnings for estrogen apply, and both carry the same boxed warning title. Both discuss adding a progestin for a woman with a uterus, use the lowest dose for the shortest time, and talk about the need for treatment regularly, for example every 3 to 6 months.12
Which, if either, fits is for your prescriber. More detail: Premarin Vaginal Cream side effects, Estrace Cream side effects, the Premarin Vaginal Cream and Estrace Cream dosing schedules and Estrace Cream vs Vagifem: how do the two vaginal estradiol products differ?.