What the label lists and what reports show
Estradiol and norethindrone side effects
Estradiol and norethindrone's FDA label: “The most common adverse reactions (incidence ≥ 5 percent) with Lopreeza are: back pain, headache, pain in the extremity, nausea, diarrhea, gastroenteritis, insomnia, emotional lability, upper respiratory tract infection, sinusitis, nasopharyngitis, weight …” FAERS holds 2,291 reports naming it through July 30, 2026; the reaction reported most often, leaving out the conditions it is used for, product-use terms and outcomes, is breast cancer (292 reports).
- Generic listed
- Boxed warning
Check it at the source: the estradiol and norethindrone FDA label on DailyMed (effective January 16, 2025, Amneal Pharmaceuticals NY LLC); the FDA FAERS public dashboard.
What does the patient leaflet say about side effects?
From the patient leaflet: What is the most important information I should know about Lopreeza (a combination of estrogen and progestin)?Do not use estrogens with progestins to prevent heart disease, heart attacks, strokes, or dementia (decline of brain function). Taking estrogens with progestins may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots. Taking estrogens with progestins may increase your chance of getting dementia, based on a study of women 65 years of age or older. Do not use estrogen-alone to prevent heart disease, heart attacks, strokes or dementia. Taking estrogen-alone may increase your chance of getting cancer of the uterus (womb). Taking estrogen-alone may increase your chances of getting strokes or blood clots. Taking estrogen-alone may increase your chance of getting dementia, based on a study of women 65 years of age or older. You and your healthcare provider should talk regularly about whether you still need treatment with Lopreeza.
Source: FDA drug label (Lopreeza), Amneal Pharmaceuticals NY LLC, effective November 30, 2017 (SPL set bf0e39cb-95e7-4831-92d2-0b3f071aeaae), via openFDA; the full label on DailyMed
What does the label list?
From the label: adverse reactionsThe most common adverse reactions (incidence ≥ 5 percent) with Lopreeza are: back pain, headache, pain in the extremity, nausea, diarrhea, gastroenteritis, insomnia, emotional lability, upper respiratory tract infection, sinusitis, nasopharyngitis, weight increase, breast pain, post-menopausal bleeding, uterine fibroid vaginal hemorrhage, ovarian cyst, endometrial thickening, viral infection, moniliasis genital, and accidental injury.
A table the label prints in its adverse reactions section without a title; its column headings name the groups compared
| Reaction | Endometrial Hyperplasia Study Lopreeza 1 mg/0.5 mg (n=295) | (12-Months) 1 mg E 2 (n=296) | Vasomotor Symptoms Study Lopreeza 1 mg/0.5 mg (n=29) | (3-Months) Placebo (n=34) | Osteoporosis Study Lopreeza 1 mg/0.5 mg (n=47) | (2-Years) Placebo (n=48) |
|---|---|---|---|---|---|---|
| Back Pain | 6% | 5% | 3% | 3% | 6% | 4% |
| Headache | 16% | 16% | 17% | 18% | 11% | 6% |
| Nausea | 3% | 5% | 10% | 0% | 11% | 0% |
| Gastroenteritis | 2% | 2% | 0% | 0% | 6% | 4% |
| Insomnia | 6% | 4% | 3% | 3% | 0% | 8% |
| Emotional Lability | 1% | 1% | 0% | 0% | 6% | 0% |
| Upper Respiratory | 18% | 15% | 10% | 6% | 15% | 19% |
| Sinusitis | 7% | 11% | 7% | 0% | 15% | 10% |
| Weight Increase | 0% | 0% | 0% | 0% | 9% | 6% |
| Breast Pain | 24% | 10% | 21% | 0% | 17% | 8% |
| Post-Menopausal Bleeding | 5% | 15% | 10% | 3% | 11% | 0% |
| Uterine Fibroid | 5% | 4% | 0% | 0% | 4% | 8% |
| Ovarian Cyst | 3% | 2% | 7% | 0% | 0% | 8% |
| Infection Viral | 4% | 6% | 0% | 3% | 6% | 6% |
| Moniliasis Genital | 4% | 7% | 0% | 0% | 6% | 0% |
| Injury Accidental | 4% | 3% | 3% | 0% | 17%* | 4%* |
| Other Events | 2% | 3% | 3% | 0% | 6% | 4% |
Rows and numbers as the label prints them, under its own column headings (the first rows of a longer table where it runs on). A reaction in a trial table is not necessarily caused by the medicine, and trials differ from everyday use.
From the label: adverse reactions, continuedThe following serious adverse reactions are discussed elsewhere in the labeling: Cardiovascular Disorders [see Boxed Warning, Warnings and Precautions ( 5.1 ) ] Malignant Neoplasms [see Boxed Warning, Warnings and Precautions ( 5.2 ) ] The most common adverse reactions (incidence ≥ 5 percent) with Lopreeza are: back pain, headache, pain in the extremity, nausea, diarrhea, gastroenteritis, insomnia, emotional lability, upper respiratory tract infection, sinusitis, nasopharyngitis, weight increase, breast pain, post-menopausal bleeding, uterine fibroid vaginal hemorrhage, ovarian cyst, endometrial thickening, viral infection, moniliasis genital, and accidental injury. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions reported with Lopreeza 1 mg/0.5 mg by investigators during clinical trials regardless of causality assessment are shown in Table 1.
Source: FDA drug label, Amneal Pharmaceuticals NY LLC, effective January 16, 2025 (SPL set 966ac064-9eb7-4d15-b271-a7880ed1e79a), via openFDA; the full label on DailyMed
What do FAERS reports show?
2,291 reports list estradiol and norethindrone among the medicines taken, each a report of something that happened, not proof the medicine caused it; 43 are coded as a death and 464 as a hospital stay. Counts follow how widely a medicine is used and watched, and they are not a measure of how risky it is. Of the 23 reactions below, 13 are named by the same term (in US spelling) in the label's adverse reactions, warnings or patient leaflet; a reaction the label does not name may still be there under another word, and a report does not show that the medicine caused it.
Reports received each year
The 25 most reported reactions
Source: FDA Adverse Event Reporting System (FAERS) via openFDA, reports through July 30, 2026; reactions as MedDRA preferred terms
What next?
- Estradiol and norethindrone: the full record
- label, generics, price, shortages, recalls
- Report a side effect to the FDA
- MedWatch
- Side effects hub
- the most reported medicines and reactions