Short answer: In the label's 12-week placebo-controlled trial, the only side effect seen in at least 3% of women on Imvexxy and more often than on placebo was headache (3.7% on 4 mcg and 2.6% on 10 mcg vs 3.1% on placebo). Vaginal discharge has been reported after approval. Imvexxy carries the estrogen boxed warning on endometrial cancer, heart and clot risks, probable dementia and breast cancer.
What Imvexxy is approved for: Imvexxy is a small, light pink, tear-shaped vaginal insert holding 4 mcg or 10 mcg of estradiol. It is approved to treat moderate to severe dyspareunia (pain with sex), a symptom of vulvar and vaginal atrophy, due to menopause (section 1.1).
Source
IMVEXXY (estradiol vaginal inserts) prescribing information, Patient Information and Instructions for Use. Mayne Pharma. DailyMed, version published October 1, 2026. DailyMed setid 6ce645c0-a550-4ae9-8dbd-3853ee8b7d26
WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, AND BREAST CANCER
Estrogen-alone therapy: a woman with a uterus who uses estrogen without a progestogen has a higher risk of endometrial cancer; adding a progestogen lowers the risk of endometrial hyperplasia, a possible precursor. Undiagnosed persistent or recurring abnormal genital bleeding after menopause is checked, including with endometrial sampling when indicated. In the Women's Health Initiative (WHI), daily oral conjugated estrogens (CE) 0.625 mg alone raised the risk of stroke and deep vein thrombosis in women 50 to 79 over 7.1 years, and probable dementia in women 65 and older over 5.2 years. Estrogen plus progestin therapy: CE 0.625 mg plus medroxyprogesterone acetate 2.5 mg raised the risk of deep vein thrombosis, pulmonary embolism, stroke, heart attack, invasive breast cancer, and probable dementia in women 65 and older. Neither is to be used to prevent heart disease or dementia. Only those oral doses were studied, so the label says the relevance to lower doses, other routes such as vaginal, or other products is not known, and the risks cannot be definitively excluded. Estrogens are prescribed at the lowest effective dose for the shortest duration consistent with treatment goals and risks.
These are the label's own numbers from the Adverse Reactions section. Where the label compares with placebo (a dummy treatment), both columns are shown, so you can see how much more often a reaction happened on Imvexxy.
| Adverse reaction | Imvexxy 4 mcg (N=191) | Imvexxy 10 mcg (N=191) | Placebo (N=192) |
|---|---|---|---|
| Headache | 7 (3.7) | 5 (2.6) | 6 (3.1) |
12-week placebo-controlled trial (N = 382 in the safety assessment); inserts daily for 14 days, then twice weekly. Headache is the only row in the table. Values are number of women (percent).
Reported after approval of the 4 mcg and 10 mcg inserts: vaginal discharge.
After 14 daily doses, mean estradiol Cavg (0-24) was 3.6 pg/mL on 4 mcg, 4.6 pg/mL on 10 mcg and 4.3 pg/mL on placebo. At Day 84, estradiol vs baseline was 4.3 vs 3.9 pg/mL on 4 mcg, 4.8 vs 5.0 on 10 mcg and 4.4 vs 4.5 on placebo.
In the 12-week trial, dyspareunia severity fell by a least-squares mean of 1.52 on 4 mcg (p = 0.0149 vs placebo) and 1.69 on 10 mcg (p < 0.0001), vs 1.28 on placebo, from group baselines of 2.6 to 2.7 (Table 3).
WHI CE alone vs placebo, women 50 to 79, per 10,000 women-years: stroke 45 vs 33; DVT 23 vs 15. CE plus MPA: stroke 33 vs 25; DVT 26 vs 13; pulmonary embolism 18 vs 8.
WHIMS, women 65 to 79: probable dementia relative risk 1.49 on CE alone (37 vs 25 cases per 10,000 women-years) and 2.05 on CE plus MPA (45 vs 22).
The Warnings and Precautions part of the label lists these. Each line gives the label's heading and what it means in plain words.
Who should not use it. Women with undiagnosed abnormal genital bleeding, current or past breast cancer, estrogen-dependent cancer, current or past DVT, pulmonary embolism, stroke or heart attack, a known anaphylactic reaction, angioedema or allergy to Imvexxy, liver impairment or disease, or protein C, protein S or antithrombin deficiency or other clotting disorders.
Systemic absorption. Imvexxy is only for vaginal use, but some estradiol may be absorbed into the body, so the warnings for systemic estrogen-alone therapy are taken into account.
Blood clots, stroke and heart attack. Estrogen alone raised stroke and DVT risk; estrogen plus progestin raised pulmonary embolism, DVT, stroke and heart attack risk. Treatment is stopped right away if one occurs or is suspected and, if feasible, at least 4 to 6 weeks before surgery linked to clots or during long immobilization.
Endometrial, breast and ovarian cancer. Estrogen alone raises endometrial cancer risk in women with a uterus, about 2- to 12-fold, and 15- to 24-fold with 5 to 10 years or more of use. CE plus MPA raised invasive breast cancer risk (relative risk 1.24). Hormone therapy has been linked to more abnormal mammograms and to ovarian cancer.
Probable dementia. In WHIMS studies of women 65 to 79, probable dementia was more common on CE alone and on CE plus MPA than on placebo. Whether this applies to younger women is unknown.
Gallbladder, calcium and vision. Estrogens are linked to gallbladder disease needing surgery (5.5), severe high calcium in breast cancer spread to bone (5.6), and blood clots in the retina, with treatment stopped pending exam for sudden vision changes (5.7).
Blood pressure, triglycerides, thyroid and other conditions. Estrogens can raise blood pressure in rare reactions, raise triglycerides with a risk of pancreatitis, raise thyroid hormone needs, cause fluid retention, and worsen endometriosis, hereditary angioedema, asthma, diabetes, epilepsy, migraine, porphyria, lupus and liver hemangiomas (sections 5.9 to 5.17).
From the Patient Information that comes with Imvexxy:
Dose Track has a side-effect log. Each entry records the symptom, a severity (none, mild, moderate, severe or life-threatening), the date and an optional note, and can be tied to a specific dose or logged on its own. The history screen shows what you logged over time, which makes it easier to tell your prescriber when a reaction started and whether it is easing. The app records what you enter; it does not judge whether a symptom is serious. For anything on the label's call-your-doctor list, call your doctor.
This page is what the FDA label says, in plain words. It is not medical advice. Follow your prescriber, and ask them or your pharmacist about anything here.