Short answer: Both put estradiol in the vagina for menopause-related vaginal changes.12 Estrace Cream is measured in grams on an applicator, each gram holding 0.1 mg estradiol, used daily at first and then 1 g one to three times a week. Vagifem is a 10 mcg insert, daily for 2 weeks, then twice a week. Both carry the estrogen boxed warning, and neither label reports a trial against the other.
| Estrace Cream | Vagifem | |
|---|---|---|
| Form | Cream, 0.1 mg estradiol per gram, with an applicator marked from 1 to 4 g1 | 10 mcg estradiol insert in a single-use applicator2 |
| Approved for | Moderate to severe symptoms of vulvar and vaginal atrophy due to menopause1 | Atrophic vaginitis due to menopause2 |
| Starting dose | 2 to 4 g daily for one or two weeks, then about half that for a similar period1 | One insert daily for 2 weeks2 |
| Maintenance | 1 g one to three times a week once the vaginal lining has recovered1 | One insert twice a week, for example Tuesday and Friday2 |
| Side effects in the label | No percentages; the Patient Information lists headache, breast pain, spotting, and vaginal burning, irritation and itching among the common ones1 | 12-month trial: vaginal yeast infection 8% vs 3% on placebo, vulvovaginal itching 8% vs 2%, back pain 7% vs 2%2 |
| Missed dose | No rule in the label1 | No rule in the label2 |
| Boxed warning | Endometrial cancer, cardiovascular disorders, breast cancer and probable dementia1 | Endometrial cancer, cardiovascular disorders, probable dementia and breast cancer2 |
Both labels say some estradiol is absorbed into the body, so the warnings for estrogen taken by mouth are taken into account.12 The boxed findings come from Women's Health Initiative studies of oral conjugated estrogens with or without medroxyprogesterone. The Vagifem label says how these apply to lower doses or other routes is not known and the risks cannot be ruled out; the Estrace Cream label says they should be assumed similar for other doses and forms.21 Both say a woman with a uterus generally has a progestin or progestogen considered, to lower the risk of cancer of the uterus.12
Both list who should not use them, including women with undiagnosed genital bleeding, breast cancer, past blood clots, stroke or heart attack, or liver disease.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: Estrace Cream side effects, Vagifem side effects, the Estrace Cream and Vagifem dosing schedules, and Imvexxy vs Vagifem: how do the two vaginal estradiol inserts differ?.