Short answer: In pooled trials, the most common Angeliq side effects were breast pain or discomfort (17.9% on the 1 mg estradiol strength, 6.2% on 0.5 mg), genital tract bleeding (14.0% and 2.5%), abdominal pain and headache. In a placebo-controlled trial of the low strength, yeast infections were 5.5% vs 0.6%. Angeliq can raise potassium, and carries a boxed warning on blood clots, stroke, breast cancer, dementia and endometrial cancer.
What Angeliq is approved for: Angeliq combines estradiol (E2) with the progestin drospirenone (DRSP), for a woman with a uterus. Both strengths treat moderate to severe hot flashes due to menopause, and the 0.5 mg DRSP/1 mg E2 strength also treats moderate to severe vulvar and vaginal atrophy symptoms due to menopause (sections 1.1, 1.2). Drospirenone has antialdosterone activity, which can raise potassium (section 5.2).
Source
ANGELIQ (drospirenone and estradiol) tablets, prescribing information and Patient Information. Bayer HealthCare Pharmaceuticals. DailyMed, version published March 3, 2026. DailyMed setid 761834c2-6b61-4583-84c2-f1ca4a97c4f2
WARNING: CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, BREAST CANCER, and ENDOMETRIAL CANCER
Estrogen plus progestin therapy: in the Women's Health Initiative (WHI), daily oral conjugated estrogens (CE) 0.625 mg plus medroxyprogesterone acetate (MPA) 2.5 mg raised the risk of deep vein thrombosis, pulmonary embolism, stroke and heart attack in women 50 to 79 over 5.6 years, and of invasive breast cancer; the WHI Memory Study found a higher risk of probable dementia in women 65 and older. Estrogen-alone therapy: a woman with a uterus who uses estrogen without a progestogen has a higher risk of endometrial cancer, and CE alone raised the risk of stroke, DVT and probable dementia. Neither is to be used to prevent heart disease or dementia. Only those oral doses were studied, so the label says the relevance to other doses, routes or products is not known and the risks cannot be definitively excluded. 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 Angeliq.
| Adverse reaction | Angeliq 0.25 mg DRSP/0.5 mg E2 (N=183) | Placebo (N=180) |
|---|---|---|
| Gastrointestinal and abdominal pains | 11 (6.0) | 5 (2.8) |
| Headache | 11 (6.0) | 9 (5.0) |
| Vulvovaginal fungal infections | 10 (5.5) | 1 (0.6) |
| Breast pain | 6 (3.3) | 1 (0.6) |
| Nausea | 6 (3.3) | 2 (1.1) |
| Diarrhea | 4 (2.2) | 1 (0.6) |
| Peripheral edema | 4 (2.2) | 2 (1.1) |
12-week placebo-controlled trial (3 cycles of 28 days); 183 women took Angeliq 0.25 mg/0.5 mg and 180 took placebo. Over half had had a hysterectomy. Values are number of women (percent). Breast pain includes breast tenderness and nipple pain.
| Adverse reaction | Angeliq with 1 mg E2 (N=2842) | Angeliq with 0.5 mg E2 (N=853) |
|---|---|---|
| Breast pain or discomfort | 508 (17.9) | 53 (6.2) |
| Female genital tract bleeding | 397 (14.0) | 21 (2.5) |
| Gastrointestinal and abdominal pain | 186 (6.5) | 31 (3.6) |
| Cervical polyp | 34 (1.2) | 3 (0.4) |
| Emotional lability | 35 (1.2) | 11 (1.3) |
| Migraine | 28 (1.0) | 5 (0.6) |
Pooled data: 13 trials of formulations with 1 mg E2 (0.5 to 3.0 mg DRSP) and 2 trials with 0.5 mg E2 (0.25 to 0.5 mg DRSP). No placebo column. Values are number of women (percent).
The most common reasons for stopping in controlled trials were abdominal pain, headache, postmenopausal bleeding, breast tenderness and weight increase. Common reactions were generally more frequent on the 1 mg E2 strength than on 0.5 mg E2.
After up to 12 months, endometrial hyperplasia was 0 of 489 women on Angeliq 0.25 mg/0.5 mg and 0 of 227 on 0.5 mg/1 mg, vs 8 of 226 (4%) on 1 mg estradiol alone (Table 5).
At one year, about 22% of women on 0.5 mg/1 mg and 15% on 0.25 mg/0.5 mg had any uterine bleeding or spotting; the proportion fell over time.
Reported after approval: hypersensitivity reactions (rash, itching, hives), breast cancer, and venous and arterial blood clots including pulmonary embolism, heart attack and stroke.
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 DVT, pulmonary embolism, stroke or heart attack, kidney impairment, liver impairment or disease, adrenal insufficiency, protein C, protein S or antithrombin deficiency or other clotting disorders, or a known anaphylactic reaction or angioedema to Angeliq.
High potassium. Drospirenone has antialdosterone activity and can raise potassium in high-risk patients. The label urges caution with other drugs that raise potassium, such as NSAIDs, potassium-sparing diuretics, potassium supplements, ACE inhibitors, ARBs, heparin and aldosterone antagonists, and suggests considering potassium checks in the first month with long-term strong CYP3A4 inhibitors.
Blood clots, stroke and heart attack. Estrogen plus progestin raised the risk of pulmonary embolism, DVT, stroke and heart attack in the WHI. Treatment is stopped right away if one occurs or is suspected and, if feasible, 4 to 6 weeks before surgery linked to clots or during long immobilization.
Breast, endometrial and ovarian cancer. The WHI found more invasive breast cancer on CE plus MPA, and hormone therapy has been linked to more abnormal mammograms. Estrogen alone raises endometrial cancer risk in women with a uterus; adding a progestogen lowers hyperplasia risk. Hormone therapy has also been linked to ovarian cancer.
Probable dementia. In WHIMS studies of women 65 to 79, probable dementia was more common on CE plus MPA and on CE alone than on placebo. Whether this applies to younger women is unknown.
Low sodium. As an aldosterone antagonist, drospirenone may increase the possibility of hyponatremia (low sodium) in high-risk women.
Other estrogen risks. Estrogens are linked to gallbladder disease, high calcium in breast cancer spread to bone, retinal blood clots, raised blood pressure, high triglycerides with pancreatitis, thyroid changes and fluid retention, and can worsen endometriosis, hereditary angioedema and other conditions (sections 5.5 to 5.17).
From the Patient Information that comes with Angeliq:
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.