Short answer: In the label's 1-year trial of women with a uterus, common Premarin side effects included vaginal bleeding (13% on 0.625 mg vs 0% on placebo), breast pain (11% vs 8%), abdominal pain (11% vs 6%), flatulence, back pain and endometrial hyperplasia (5% vs 0%). Premarin carries a boxed warning on endometrial cancer, stroke and blood clots, breast cancer with a progestin, and probable dementia.
What Premarin is approved for: Premarin is a mixture of estrogens approved to treat moderate to severe hot flashes (vasomotor symptoms) and vulvar and vaginal atrophy due to menopause; low estrogen from hypogonadism, castration or primary ovarian failure; for palliation only, certain metastatic breast cancer and advanced androgen-dependent prostate cancer; and to prevent postmenopausal osteoporosis (section 1). For vaginal symptoms alone, topical vaginal products are considered; for osteoporosis prevention alone, only women at significant risk, with non-estrogen medicines carefully considered.
Source
PREMARIN (conjugated estrogens tablets, USP) for oral administration, prescribing information and Patient Information. Wyeth Pharmaceuticals (Pfizer). DailyMed, version published June 3, 2026. DailyMed setid 258e1602-a3cf-4ccc-ca80-73dbbfb812ff
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 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 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 to be similar for other doses of CE and other forms of estrogen. 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 Premarin.
| Adverse reaction | Premarin 0.625 mg (n=348) | Premarin 0.45 mg (n=338) | Premarin 0.3 mg (n=326) | Placebo (n=332) |
|---|---|---|---|---|
| Abdominal pain | 38 (11) | 28 (8) | 30 (9) | 21 (6) |
| Asthenia | 16 (5) | 8 (2) | 14 (4) | 3 (1) |
| Back pain | 18 (5) | 11 (3) | 13 (4) | 4 (1) |
| Headache | 45 (13) | 47 (14) | 44 (13) | 46 (14) |
| Pain | 17 (5) | 10 (3) | 12 (4) | 14 (4) |
| Flatulence | 22 (6) | 18 (5) | 13 (4) | 8 (2) |
| Nausea | 16 (5) | 10 (3) | 15 (5) | 16 (5) |
| Depression | 17 (5) | 15 (4) | 10 (3) | 17 (5) |
| Insomnia | 16 (5) | 10 (3) | 13 (4) | 14 (4) |
| Breast pain | 37 (11) | 39 (12) | 24 (7) | 26 (8) |
| Endometrial hyperplasia | 16 (5) | 8 (2) | 1 (0) | 0 |
| Leukorrhea | 17 (5) | 17 (5) | 12 (4) | 6 (2) |
| Vaginal hemorrhage | 46 (13) | 13 (4) | 6 (2) | 0 |
| Vaginitis | 18 (5) | 7 (2) | 9 (3) | 1 (0) |
First year of a 2-year trial of 2,333 postmenopausal women with a uterus aged 40 to 65; 1,012 took CE and 332 took placebo. Shown are rows at 5% or more in any group; the full table also lists reactions at 1% to 4%. Cells are number of women (percent). Leukorrhea is vaginal discharge; vaginal hemorrhage is vaginal bleeding.
Other rows in Table 1 (0.625 mg vs placebo): pruritus 11 (3) vs 3 (1); leg cramps 10 (3) vs 4 (1); weight gain 11 (3) vs 14 (4); vaginal moniliasis 14 (4) vs 5 (2); metrorrhagia 11 (3) vs 1 (0); uterine spasm 11 (3) vs 2 (1); dysmenorrhea 12 (3) vs 2 (1).
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.
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 2- to 4-fold increase in gallbladder disease needing surgery has been reported in postmenopausal women taking estrogens.
Reported after approval: abnormal uterine bleeding, larger fibroids, breast tenderness, enlargement and discharge, blood clots, gallbladder disease, pancreatitis, melasma that may persist after stopping, loss of scalp hair, contact lens intolerance, mood changes, weight changes, changes in libido and hives, 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. People with undiagnosed abnormal genital bleeding, current or past breast cancer (except selected patients treated for metastatic disease), estrogen-dependent cancer, current or past blood clots, stroke or heart attack, a known anaphylactic reaction or angioedema with Premarin, liver impairment or disease, or protein C, protein S or antithrombin deficiency or other inherited clotting disorders.
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. 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 CE with or without MPA.
Anaphylaxis and angioedema. Anaphylaxis needing emergency care, within minutes to hours of a dose, and angioedema of the tongue, larynx, face, hands and feet have been reported after approval. Anyone who has such a reaction does not take Premarin again.
Vision problems. Blood clots in the retina have been reported. The medicine 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 (5.10). It is stopped if jaundice from bile blockage returns (5.11). Estrogen can cause severe high calcium in breast cancer that has spread to bone (5.5) and low calcium in hypoparathyroidism (5.14).
Thyroid, fluid and other conditions. Women on thyroid hormone may need higher doses. Estrogen can cause fluid retention and may worsen hereditary angioedema, endometriosis, asthma, diabetes, epilepsy, migraine, porphyria, lupus and liver hemangiomas (sections 5.12 to 5.17).
From the Patient Information that comes with Premarin:
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.