Short answer: In the label's controlled studies, the most common side effects of norethindrone acetate and ethinyl estradiol were breast pain (9.0% on 0.5/2.5 and 7.8% on 1/5 vs 3.6% on placebo), abdominal pain (5.3% and 6.8% vs 1.2%), headache and generalized edema. Fyavolv carries a boxed warning on blood clots, stroke, heart attack, breast cancer, probable dementia and endometrial cancer.
What Fyavolv is approved for: Fyavolv combines a progestin (norethindrone acetate) with a low dose of the estrogen ethinyl estradiol in one daily tablet. It is approved for a woman with a uterus to treat moderate to severe hot flashes due to menopause and to prevent postmenopausal osteoporosis (sections 1.1, 1.2). For bone alone, the label says to first consider non-estrogen medicines.
Source
FYAVOLV (norethindrone acetate and ethinyl estradiol tablets USP), prescribing information and Patient Information. Lupin Pharmaceuticals. DailyMed, version published January 13, 2026. DailyMed setid 772c86d7-10a4-48c5-8c19-f8aac68f5ab4
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 pulmonary embolism, deep vein thrombosis, 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 over 4 years. 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 Fyavolv.
| Adverse reaction | Placebo (N=247) | NA/EE 0.5/2.5 (N=244) | NA/EE 1/5 (N=258) |
|---|---|---|---|
| Body as a whole | 23 (12.8) | 30 (16.9) | 30 (15.7) |
| Edema, generalized | 10 (4.0) | 12 (4.9) | 11 (4.3) |
| Headache | 12 (4.9) | 14 (5.7) | 16 (6.2) |
| Digestive system | 8 (4.4) | 17 (9.6) | 25 (13.1) |
| Abdominal pain | 3 (1.2) | 13 (5.3) | 14 (6.8) |
| Urogenital system | 20 (11.1) | 34 (19.2) | 45 (23.6) |
| Breast pain | 9 (3.6) | 22 (9.0) | 20 (7.8) |
Controlled clinical studies of norethindrone acetate and ethinyl estradiol (NA/EE). Cells are number of women (percent). The label notes that the body-system totals may count fewer women than the reactions below them, because one woman may have had more than one reaction.
Endometrial hyperplasia, a possible precursor of endometrial cancer, has been reported at a rate of approximately 1 percent or less with Fyavolv.
In a 2-year study, endometrial hyperplasia at month 24 was 0 on NA/EE 0.5/2.5 and 1/5, 1 on placebo, 0 on ethinyl estradiol 2.5 mcg alone and 2 on ethinyl estradiol 5 mcg alone (Table 5).
Lumbar spine bone density (measured by QCT) rose 3.1 percent from baseline to month 24 on NA/EE 1/5, and fell 6.3 percent on placebo. The label notes QCT shows larger changes than DXA.
WHI CE plus MPA vs placebo, per 10,000 women-years: stroke 33 vs 25; DVT 26 vs 13; pulmonary embolism 18 vs 8; all VTE 35 vs 17. Invasive breast cancer 41 vs 33 (5.2).
WHIMS, women 65 to 79 on CE plus MPA: 40 vs 21 women diagnosed with probable dementia over 4 years; relative risk 2.05, 45 vs 22 cases per 10,000 women-years.
Reported after approval include bleeding pattern changes, breakthrough bleeding and spotting, breast tenderness and enlargement, blood clots, heart attack, stroke, raised blood pressure, nausea, gallbladder disease, melasma, scalp hair loss, migraine, mood changes, weight change, edema and hypersensitivity reactions.
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, active or past DVT, pulmonary embolism, stroke or heart attack, a known anaphylactic reaction, angioedema or hypersensitivity to Fyavolv, liver impairment or disease, or protein C, protein S or antithrombin deficiency or other clotting disorders.
Blood clots, stroke and heart attack. Estrogen plus progestin raised the risk of pulmonary embolism, DVT, stroke and heart attack, and treatment is stopped right away if one occurs or is suspected. If feasible, estrogens are stopped 4 to 6 weeks before surgery linked to clots or during long immobilization.
Breast, endometrial and ovarian cancer. CE plus MPA raised invasive breast cancer risk in the WHI (relative risk 1.24), and hormone therapy has been linked to more abnormal mammograms. Estrogen without a progestogen raises endometrial cancer risk 2 to 12 times in women with a uterus. A meta-analysis linked current hormone therapy to a higher ovarian cancer risk (relative risk 1.41).
Probable dementia. In women 65 to 79, probable dementia was more common on CE plus MPA (relative risk 2.05) and on CE alone (1.49) than on placebo. Whether this applies to younger women is unknown.
Gallbladder, calcium and vision. Estrogens are linked to a 2- to 4-fold rise in gallbladder disease needing surgery (5.4), severe high calcium in breast cancer spread to bone (5.5), and blood clots in the retina, with treatment stopped pending exam for sudden vision changes (5.6).
Blood pressure, triglycerides and liver. Estrogens can raise blood pressure in rare reactions (5.8) and raise triglycerides with a risk of pancreatitis (5.9). Treatment is stopped if cholestatic jaundice comes back (5.10).
Thyroid, fluid and other conditions. Women on thyroid hormone may need higher doses. Estrogens can cause fluid retention, low calcium in hypoparathyroidism, and worsen endometriosis, hereditary angioedema, asthma, diabetes, epilepsy, migraine, porphyria, lupus and liver hemangiomas (sections 5.11 to 5.16).
From the Patient Information that comes with Fyavolv:
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.