Short answer: In the label's two 12-week trials, the most common EstroGel side effects were breast pain (10.7% vs 8.2% on placebo), headache (9.5% vs 2.7%) and flatulence (5.4% vs 4.1%). Application site reactions were reported by 0.6%. EstroGel carries the estrogen boxed warning on endometrial cancer, stroke and blood clots, probable dementia and, with a progestin, breast cancer.
What EstroGel is approved for: EstroGel is an estrogen gel approved to treat moderate to severe hot flashes (vasomotor symptoms) and moderate to severe symptoms of vulvar and vaginal atrophy due to menopause (section 1). For vaginal symptoms alone, the label says topical vaginal products are considered first.
Source
ESTROGEL 0.06% (estradiol gel) for topical use, prescribing information, Patient Information and Instructions for Use. Ascend Therapeutics US. DailyMed, version published June 1, 2026. DailyMed setid 762ac371-bb8b-47e7-b48f-e80d452c9dd4
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 the WHI Memory Study found a higher risk of probable dementia in women 65 and older over 5.2 years. Estrogen plus progestin therapy: daily CE 0.625 mg plus medroxyprogesterone acetate (MPA) 2.5 mg raised the risk of pulmonary embolism, deep vein thrombosis, stroke, heart attack and invasive breast cancer, and of 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 whether the findings apply to other doses, routes such as a gel, or products is not known. Estrogens, with or without progestogens, 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 EstroGel.
| Adverse drug reaction | EstroGel 0.06% 1.25 g/day (n=168) | Placebo (n=73) |
|---|---|---|
| Headache | 9.5 | 2.7 |
| Flatulence | 5.4 | 4.1 |
| Breast pain | 10.7 | 8.2 |
Two well-controlled 12-week trials of EstroGel 1.25 g per day against placebo gel. Headache is listed under Body as a Whole, flatulence under Digestive System and breast pain under Urogenital System.
Application site reactions were reported by 0.6% of women on 1.25 g of EstroGel in the 2 controlled trials. Other skin reactions, such as itching and rash, were also noted.
WHI, estrogen alone (oral CE 0.625 mg): stroke 45 vs 33 per 10,000 women-years on placebo; blood clots (VTE) 30 vs 22, with deep vein thrombosis 23 vs 15. With a progestin (CE plus MPA): stroke 33 vs 25; VTE 35 vs 17; pulmonary embolism 18 vs 8.
Endometrial cancer risk with estrogen alone in a woman with a uterus is about 2 to 12 times that of non-users, and 15 to 24 times with 5 to 10 years or more of use, persisting at least 8 to 15 years after stopping.
WHI estrogen plus progestin: invasive breast cancer 41 vs 33 per 10,000 women-years (relative risk 1.24). Estrogen alone was not linked to more invasive breast cancer in WHI (relative risk 0.8).
WHIMS, women 65 to 79: probable dementia 37 vs 25 per 10,000 women-years with estrogen alone, and 45 vs 22 with estrogen plus progestin. It is unknown whether this applies to younger women.
Washing the application site 1 hour after use lowered average 24-hour estradiol levels by 22%. Moisturizer lotion applied 1 hour after the gel raised estradiol exposure (AUC) by 38% and peak level by 73%; sunscreen lowered both by 16%.
Reported after approval: breast pain, tenderness and breast cancer, endometrial cancer, deep vein thrombosis, nausea, bloating, hair loss, rash, application site dryness, pain or discoloration, retinal vein occlusion, dizziness, insomnia, meningioma, weight gain and angioedema, among others.
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 blood clots, stroke or heart attack, liver impairment or disease, protein C, protein S or antithrombin deficiency or other inherited clotting disorders, or a known allergic reaction to EstroGel.
Stroke, blood clots and heart attack. Estrogen is stopped right away if a stroke, blood clot or heart attack occurs or is suspected. If feasible, it is stopped 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. Estrogen plus progestin raised breast cancer risk in WHI, and observational studies show a smaller rise with estrogen alone. A meta-analysis linked current hormone therapy to ovarian cancer (relative risk 1.41). Yearly breast exams by a provider and monthly self-exams are advised.
Probable dementia. WHIMS found a higher risk of probable dementia in women 65 to 79 on oral estrogen with or without a progestin.
Gallbladder disease. A 2- to 4-fold rise in gallbladder disease needing surgery has been reported in postmenopausal women taking estrogens.
Vision problems. Blood clots in the retina have been reported. EstroGel is stopped pending exam for sudden vision loss, bulging eyes, double vision or migraine, and permanently if papilledema or retinal vessel lesions are found.
Triglycerides, liver and calcium. In women with high triglycerides, estrogen can raise them and cause pancreatitis (5.9). EstroGel is stopped if jaundice from bile blockage returns (5.10). Estrogen can cause severe high calcium in breast cancer that has spread to bone (5.5) and low calcium in hypoparathyroidism (5.13).
Thyroid, fluid and other conditions. Women on thyroid hormone may need higher doses. Estrogen can cause fluid retention and may worsen asthma, diabetes, epilepsy, migraine, porphyria, lupus, liver hemangiomas, endometriosis and hereditary angioedema (sections 5.11 to 5.16).
Flammable gel and lotions. EstroGel contains alcohol, so fire, flame and smoking are avoided until it has dried. Moisturizer lotion applied one hour after EstroGel significantly increased estradiol absorption (section 5.18).
From the Patient Information that comes with EstroGel:
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.