Hormone Replacement Therapy (HRT) Side Effects Side effects that can occur with all forms of estrogen but are more frequent with oral estrogen include: Headaches. Nausea. Vaginal discharge. Fluid retention. Weight gain. Breast tenderness. Spotting or darkening of the skin, particularly on the face. Deep venous thrombosis. Pulmonary emboli. Rarely, an increased growth of preexisting uterine fibroids or a worsening of endometriosis. Some of these side effects, such as headaches, nausea, fluid retention, weight gain, and breast tenderness, may go away after a few weeks of use. The estrogen patch (transdermal estrogen) may cause skin irritation. An estrogen ring must be replaced every 3 months. If the ring falls out at any time during the 3-month treatment period, you may rinse it with lukewarm water and reinsert it. Vaginal cream may be used by women with liver or gallbladder disease. See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.) What to Think About Recent studies are recommending that hormone replacement therapy using estrogen and progestin (HRT) be used only for short-term treatment of menopausal symptoms. Studies involving women taking estrogen without progestin (ERT) are still in progress. While ERT alone increases the risk of endometrial cancer, estrogen taken in combination with progestin (HRT) does not increase the risk. Women who have had a hysterectomy do not have an increased risk of uterine cancer. A woman who has a uterus and is unable to tolerate the side effects of progestin in hormone replacement therapy (HRT) may consider estrogen-only replacement therapy (ERT) if testing shows no abnormalities of the endometrium. Close observation for precancerous changes of the endometrium is required, including an annual pelvic exam and an annual endometrial biopsy. No studies have compared different types estrogens to see whether there is a difference in their effects. Some women prefer estrogens that do not come from animal products.