Short answer: In the label's 12-week placebo-controlled trial, the most common Evamist side effects were headache (9% to 12% across 1 to 3 sprays vs 5% to 9% on placebo), breast tenderness (5% to 7%), nipple pain, back pain and nasopharyngitis. Its boxed warning covers endometrial cancer, stroke, blood clots, probable dementia, breast cancer, and breast changes in children exposed to the spray on a user's skin.
What Evamist is approved for: Evamist is an estradiol spray applied to the inner forearm. It is approved to treat moderate to severe hot flashes (vasomotor symptoms) due to menopause (section 1.1). The label says a woman with a uterus generally also needs a progestogen to reduce the risk of endometrial cancer (section 2).
Source
EVAMIST (estradiol transdermal spray), prescribing information, Patient Information and Instructions for Use. Padagis. DailyMed, version published November 1, 2024. DailyMed setid 9a0aa631-133d-406b-9d32-8a1a99af4e50
WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, BREAST CANCER, and UNINTENTIONAL SECONDARY EXPOSURE TO ESTROGEN
Estrogen-alone therapy: a woman with a uterus who uses estrogen without a progestogen has a higher risk of endometrial cancer. 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, and the WHI Memory Study found a higher risk of probable dementia in women 65 and older. Estrogen plus progestin therapy: CE plus medroxyprogesterone acetate (MPA) raised the risk of pulmonary embolism, DVT, stroke, heart attack, invasive breast cancer and probable dementia. Neither is to be used to prevent heart disease or dementia. Unintentional secondary exposure: breast budding and breast masses in young girls, and breast growth and masses in young boys, have been reported after contact with skin where a woman applied Evamist; most cases resolved once the exposure ended. Women keep children from touching the application site. 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 Evamist.
| Adverse reaction | Placebo, 1 spray (N=77) | Evamist 1 spray (N=76) | Placebo, 2 sprays (N=76) | Evamist 2 sprays (N=74) | Placebo, 3 sprays (N=75) | Evamist 3 sprays (N=76) |
|---|---|---|---|---|---|---|
| Headache | 4 (5) | 7 (9) | 5 (7) | 9 (12) | 7 (9) | 8 (11) |
| Breast tenderness | 0 (0) | 4 (5) | 4 (5) | 5 (7) | 0 (0) | 4 (5) |
| Nipple pain | 0 (0) | 2 (3) | 0 (0) | 5 (7) | 0 (0) | 1 (1) |
| Nausea | 5 (7) | 1 (1) | 1 (1) | 2 (3) | 4 (5) | 2 (3) |
| Nasopharyngitis | 1 (1) | 4 (5) | 2 (3) | 3 (4) | 1 (1) | 1 (1) |
| Back pain | 1 (1) | 2 (3) | 2 (3) | 4 (5) | 1 (1) | 2 (3) |
| Arthralgia | 1 (1) | 1 (1) | 4 (5) | 1 (1) | 0 (0) | 3 (4) |
12-week trial of 454 postmenopausal women. Each spray dose (1, 2 or 3 sprays a day) was compared with its own placebo group. Cells are number of women (percent).
Application site reactions were reported in 3 of 226 women (1.3%) treated with Evamist.
Daily moderate to severe hot flashes fell by 8.10, 8.66 and 8.44 a day at week 12 on 1, 2 and 3 sprays, vs 4.76, 6.19 and 5.32 on the matching placebos (Table 3).
Sunscreen applied about one hour after Evamist lowered estradiol absorption by 11 percent; sunscreen applied about one hour before made no significant change.
After approval, breast budding and masses in young girls and breast growth and masses in young boys were reported after unintentional contact with Evamist; most resolved once exposure ended.
Also reported after approval: nipple and areola darkening, usually on the same side as the forearm used, along with breast swelling, dizziness, taste changes, eye irritation, stomach upset, vaginal bleeding, mood changes, insomnia, cough, rash, hair loss, weight gain and fatigue.
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, active or past DVT, pulmonary embolism, stroke or heart attack, a known anaphylactic reaction, angioedema or hypersensitivity to Evamist, liver impairment or disease, or protein C, protein S or antithrombin deficiency or other clotting disorders.
Exposure of children and others. Children who touch skin where Evamist was sprayed can show early breast development. Women cover the site with clothing if someone may touch it. If a child shows unexpected sexual development, the child is checked by a provider, and Evamist is stopped if safe use cannot be assured.
Blood clots, stroke and heart attack. Estrogen alone raised the risk of stroke and DVT; estrogen plus progestin raised the risk of pulmonary embolism, DVT, stroke and heart attack. Treatment is stopped right away if one occurs or is suspected, and if feasible 4 to 6 weeks before surgery linked to clots.
Endometrial, breast and ovarian cancer. Estrogen without a progestogen raises endometrial cancer risk in women with a uterus. CE plus MPA raised invasive breast cancer risk in the WHI, and hormone therapy has been linked to more abnormal mammograms and to ovarian cancer.
Probable dementia. In women 65 to 79, probable dementia was 37 vs 25 per 10,000 women-years on CE alone and 45 vs 22 on CE plus MPA, compared with placebo. Whether this applies to younger women is unknown.
Gallbladder, calcium, vision and blood pressure. Estrogens are linked to a 2- to 4-fold rise in gallbladder disease needing surgery (5.5), severe high calcium in breast cancer spread to bone (5.6), retinal blood clots (5.7), rare blood pressure rises (5.9) and high triglycerides with pancreatitis (5.10).
Thyroid, fluid and other conditions. Women on thyroid hormone may need higher doses. Estrogens can cause fluid retention, low calcium in hypoparathyroidism, and worsen endometriosis, hereditary angioedema, asthma, diabetes, epilepsy, migraine, porphyria, lupus and liver hemangiomas (sections 5.12 to 5.17). The spray contains alcohol and is flammable until dry (5.18).
From the Patient Information that comes with Evamist:
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.