Short answer: The Estrace Cream label gives no side effect percentages. Its Patient Information lists headache, breast pain, irregular vaginal bleeding or spotting, stomach cramps and bloating, nausea, hair loss, fluid retention, vaginal yeast infection and vaginal burning, irritation and itching as less serious but common. Estrace Cream carries the estrogen boxed warning on endometrial cancer, stroke and blood clots, breast cancer and probable dementia.
What Estrace Cream is approved for: Estrace Cream is an estrogen cream approved to treat moderate to severe symptoms of vulvar and vaginal atrophy due to menopause (Indications and Usage). Each gram contains 0.1 mg estradiol (Description). The label says some estrogen is absorbed into the body, so the warnings for oral estrogen are taken into account (Warnings).
Source
ESTRACE (estradiol vaginal cream USP 0.01%), prescribing information and Patient Information. Allergan (AbbVie). DailyMed, version published November 5, 2024. DailyMed setid dfc41fcd-c5ba-4b25-b647-cf04d3988b3e
WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER and PROBABLE DEMENTIA
Estrogen-alone therapy: a woman with a uterus who uses estrogen without a progestin has a higher risk of endometrial cancer; adding a progestin lowers the risk of endometrial hyperplasia, a possible precursor. Undiagnosed persistent or recurring abnormal genital bleeding after menopause is checked, including 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 deep vein thrombosis, pulmonary embolism, 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. Without comparable data, the label says these risks should be assumed similar for other doses and dosage forms of estrogens. Estrogens, with or without progestins, 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 Estrace Cream.
| Body system | Reactions the label lists |
|---|---|
| Genitourinary system | Abnormal uterine bleeding or spotting; dysmenorrhea or pelvic pain; increase in size of uterine leiomyomata; vaginitis, including vaginal candidiasis; change in cervical secretion; cystitis-like syndrome; application site reactions of vulvovaginal discomfort including burning and irritation; genital pruritus; ovarian cancer; endometrial hyperplasia; endometrial cancer |
| Breasts | Tenderness, enlargement, pain, nipple discharge, fibrocystic breast changes; breast cancer |
| Cardiovascular | Deep and superficial venous thrombosis; pulmonary embolism; myocardial infarction; stroke; increase in blood pressure |
| Gastrointestinal | Nausea, vomiting; abdominal cramps, bloating; increased incidence of gallbladder disease |
| Skin | Chloasma that may persist when drug is discontinued; loss of scalp hair; hirsutism; rash |
| Eyes | Retinal vascular thrombosis, intolerance to contact lenses |
| Central nervous system | Headache; migraine; dizziness; mental depression; nervousness; mood disturbances; irritability; dementia |
| Miscellaneous | Increase or decrease in weight; glucose intolerance; edema; arthralgias; leg cramps; changes in libido; urticaria; exacerbation of asthma; increased triglycerides; hypersensitivity |
The label lists these as reactions reported with estrogen and/or progestin therapy. It gives no percentages and no placebo comparison.
WHI, estrogen alone (oral CE 0.625 mg): stroke 45 vs 33 per 10,000 women-years on placebo; deep vein thrombosis 23 vs 15. With a progestin (CE plus MPA): stroke 33 vs 25; blood clots (VTE) 35 vs 17; pulmonary embolism 18 vs 8.
Endometrial cancer risk with unopposed estrogen in a woman with a uterus is about 2 to 12 times that of non-users, and 15 to 24 times with five to ten 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 0.80).
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.
A meta-analysis linked current hormone therapy for menopause symptoms to ovarian cancer (relative risk 1.41). Gallbladder disease needing surgery was reported 2 to 4 times more often in postmenopausal women taking estrogens.
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 dysfunction or disease, inherited clotting disorders, a known anaphylactic reaction or angioedema to Estrace Cream, or known or suspected pregnancy.
Absorbed into the body. Some estradiol may be absorbed from the vagina into the bloodstream, so the label says the warnings, precautions and side effects of oral estrogen are taken into account.
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. 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 and older on oral estrogen with or without a progestin.
Calcium, vision and allergic reactions. Estrogen can cause severe high calcium in women with breast cancer that has spread to bone. Blood clots in the retina have been reported; the medicine is stopped pending exam for sudden vision loss, bulging eyes, double vision or migraine. Anaphylaxis and angioedema have been reported with oral estrogen, and estrogen may worsen hereditary angioedema.
Other conditions. Estrogen may raise triglycerides and cause pancreatitis in women with high triglycerides, may require higher thyroid hormone doses, can cause fluid retention, and may worsen asthma, diabetes, epilepsy, migraine, porphyria, lupus, liver hemangiomas and endometriosis.
From the Patient Information that comes with Estrace Cream:
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.