Short answer: The Patient Information lists headache, breast pain, irregular vaginal bleeding or spotting, stomach cramps or bloating, nausea and vomiting, and hair loss as common estradiol side effects; the prescribing information gives no percentages. The label has a boxed warning: estrogens raise the risk of uterine cancer, and the WHI study of estrogen plus progestin found more heart attacks, strokes, breast cancer, blood clots and dementia.
What Estradiol Tablets is approved for: Oral estradiol tablets are approved to treat moderate to severe menopausal hot flashes and night sweats; moderate to severe vulvar and vaginal atrophy from menopause; low estrogen from hypogonadism, castration or primary ovarian failure; to prevent postmenopausal osteoporosis in women at significant risk who cannot use non-estrogen medicines; and, for palliation only, certain metastatic breast cancer and advanced prostate cancer (Indications and Usage).
Source
Estradiol Tablets, USP 0.5 mg, 1 mg and 2 mg, prescribing information and Patient Information. Epic Pharma. DailyMed, version published October 2, 2026. DailyMed setid 9333d92f-2585-4b99-aaea-87c01c95125e
ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER; CARDIOVASCULAR AND OTHER RISKS
Close clinical surveillance of all women taking estrogens is important, and undiagnosed persistent or recurring abnormal vaginal bleeding is investigated, including endometrial sampling when indicated, to rule out cancer. There is no evidence that "natural" estrogens carry a different endometrial risk than "synthetic" estrogens at equivalent doses. Estrogens with or without progestins should not be used to prevent cardiovascular disease. The Women's Health Initiative (WHI) reported increased risks of heart attack, stroke, invasive breast cancer, pulmonary emboli and deep vein thrombosis in postmenopausal women aged 50 to 79 during 5 years of oral conjugated estrogens (CE 0.625 mg) plus medroxyprogesterone acetate (MPA 2.5 mg) vs placebo. The WHI Memory Study reported an increased risk of probable dementia in women 65 or older during 4 years of CE plus MPA; whether this applies to younger women or estrogen alone is unknown. Other doses, combinations and dosage forms were not studied in WHI and, without comparable data, these risks should be assumed to be similar. Estrogens should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
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 Estradiol Tablets.
| Body system | Reactions the label lists |
|---|---|
| Genitourinary system | Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding, spotting, dysmenorrhea; increase in size of uterine leiomyomata; vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; ovarian cancer; endometrial hyperplasia; endometrial cancer |
| Breasts | Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer |
| Cardiovascular | Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction; stroke; increase in blood pressure |
| Gastrointestinal | Nausea, vomiting; abdominal cramps, bloating; cholestatic jaundice; increased incidence of gallbladder disease; pancreatitis; enlargement of hepatic hemangiomas |
| Skin | Chloasma or melasma that may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism; pruritus, rash |
| Eyes | Retinal vascular thrombosis; steepening of corneal curvature; intolerance to contact lenses |
| Central Nervous System | Headache, migraine, dizziness; mental depression; chorea; nervousness, mood disturbances, irritability; exacerbation of epilepsy; dementia |
| Miscellaneous | Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthralgias; leg cramps; changes in libido; urticaria; angioedema; anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides |
The label says these reactions have been reported with estrogen and/or progestin therapy. It gives no percentages and no placebo comparison.
| Event | Relative Risk CE/MPA vs placebo (95% CI) | Placebo n = 8102 | CE/MPA n = 8506 |
|---|---|---|---|
| CHD events | 1.29 (1.02 to 1.63) | 30 | 37 |
| Invasive breast cancer | 1.26 (1 to 1.59) | 30 | 38 |
| Stroke | 1.41 (1.07 to 1.85) | 21 | 29 |
| Pulmonary embolism | 2.13 (1.39 to 3.25) | 8 | 16 |
| Deep vein thrombosis | 2.07 (1.49 to 2.87) | 13 | 26 |
| Colorectal cancer | 0.63 (0.43 to 0.92) | 16 | 10 |
| Hip fracture | 0.66 (0.45 to 0.98) | 15 | 10 |
| Global Index | 1.15 (1.03 to 1.28) | 151 | 170 |
This trial used oral conjugated estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg daily, not estradiol tablets; the label includes it as class information. 16,608 women aged 50 to 79, average follow-up 5.2 years. Absolute risk is per 10,000 women-years.
Endometrial cancer risk in women with a uterus using estrogen without a progestin is about 2 to 12 times that of non-users, rising to 15 to 24 times with 5 to 10 years or more of use, and the risk lasts 8 to over 15 years after stopping.
WHI estrogen plus progestin: relative risk of invasive breast cancer 1.24, 41 vs 33 cases per 10,000 women-years. WHI estrogen alone (7.1 years): relative risk 0.80.
In women 65 and older, probable dementia was diagnosed in 1.8% on CE/MPA vs 0.9% on placebo over 4 years (45 vs 22 per 10,000 women-years; relative risk 2.05).
A meta-analysis found a relative risk of 1.41 with current hormone therapy use for menopausal symptoms. In WHI, 4 vs 3 cases per 10,000 women-years (not statistically significant).
A 2- to 4-fold increase in gallbladder disease needing surgery has been reported 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 take it. People with undiagnosed abnormal genital bleeding; current, suspected or past breast cancer (except selected metastatic disease being treated); estrogen-dependent cancer; active or past blood clots in the legs or lungs; a stroke or heart attack, active or within about the past year; liver disease; allergy to the ingredients; or known or suspected pregnancy.
Heart attack, stroke and blood clots. Estrogens are stopped immediately if a heart attack, stroke or blood clot occurs or is suspected, and if feasible at least 4 to 6 weeks before surgery linked to clots or during long immobilization. In WHI, clots occurred at 34 vs 16 per 10,000 women-years on CE/MPA vs placebo.
Uterine, breast and ovarian cancer. Estrogen alone raises uterine cancer risk in women with a uterus, and adding a progestin lowers the risk of endometrial hyperplasia. Yearly breast exams and mammograms based on age and risk are part of the label's guidance.
Probable dementia. WHIMS found more probable dementia in women 65 and older on CE/MPA; whether this applies to younger women or estrogen alone is unknown.
Vision problems. Blood clots in the retina have been reported. Estrogens are paused for sudden vision loss, bulging eyes, double vision or migraine, and stopped for good if papilledema or retinal vessel lesions are found.
High calcium in breast cancer. Estrogen may cause severe high calcium in breast cancer that has spread to bone, and is stopped if it occurs.
Blood pressure, triglycerides and other conditions. Blood pressure is checked regularly. Estrogen may raise triglycerides and lead to pancreatitis in people with high triglycerides, and may worsen endometriosis, asthma, diabetes, epilepsy, migraine, porphyria, lupus and liver hemangiomas.
From the Patient Information that comes with Estradiol Tablets:
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.