Short answer: Both treat vaginal symptoms of menopause.12 Osphena (ospemifene), an estrogen agonist/antagonist, is a 60 mg tablet taken daily with food for painful sex and vaginal dryness. Vagifem is a 10 mcg estradiol insert placed in the vagina daily for 2 weeks, then twice a week, for atrophic vaginitis. Both have boxed warnings on endometrial cancer and stroke or clot risk. Neither label reports a trial against the other.
| Osphena | Vagifem | |
|---|---|---|
| Drug and form | Ospemifene 60 mg tablet, by mouth1 | Estradiol 10 mcg vaginal insert in a single-use applicator2 |
| Approved for | Moderate to severe painful sex and moderate to severe vaginal dryness from menopause1 | Atrophic vaginitis due to menopause2 |
| How used | One tablet daily with food1 | One insert daily for 2 weeks, then twice a week, for example Tuesday and Friday2 |
| Side effects in label trials | 12 weeks: hot flush 6.5% vs 2.6% on placebo, vaginal discharge 3.8% vs 0.4%, muscle spasms 1.8% vs 0.6%1 | 12 months: vaginal yeast infection 8% vs 3% on placebo, vulvovaginal itching 8% vs 2%, back pain 7% vs 2%, diarrhea 5% vs 0%2 |
| Use with other estrogen | Not used with estrogens or other estrogen agonist/antagonists1 | Is an estrogen; some is absorbed into the body2 |
| Missed dose | No instruction in the label1 | No instruction in the label2 |
| Boxed warning | Endometrial cancer and cardiovascular disorders1 | Endometrial cancer, cardiovascular disorders, probable dementia and breast cancer2 |
Osphena acts like estrogen on the lining of the uterus. In its trials of up to 15 months, thromboembolic and hemorrhagic stroke rates were 1.13 and 3.39 per thousand women-years on Osphena vs 3.15 and 0 on placebo. Up to 52 weeks, no endometrial cancer was seen on Osphena, and using a progestin with it was not studied. It is not used in women with known, suspected or past breast cancer, or with severe liver impairment.1
Vagifem is for vaginal use, but the label says some estradiol is absorbed into the body, so the warnings for estrogen taken by mouth apply. In its 12-month trial, endometrial biopsies in 172 women on Vagifem found one adenocarcinoma and one complex hyperplasia without atypia.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: Osphena side effects, Vagifem side effects, the Osphena and Vagifem dosing schedules, Osphena vs Intrarosa: how do the pill and the vaginal insert differ? and Imvexxy vs Vagifem: how do the two vaginal estradiol inserts differ?.