Side effects of estropipate include vaginal bleeding, lack of periods, prolonged periods, breast pain, or changes in libido. The medication can also produce gallstones, which may result in blockage of the gallbladder resulting in abdominal pain. Estrogen therapy in general can lead to increased migraines, excessive sodium levels, and general fluid retention resulting in leg swelling. Other side effects include tan patches on the face and increased curvature of the cornea.
More serious side effects include the development of blood clots, especially in smokers, and an increased risk of uterine cancer. According to the FDA, estropipate may have a small increase in the risk of breast cancer.