Common side effects of vaginal estrogen can include: breast pain or tenderness, nausea and vomiting, heartburn, dizziness, nervousness, depression, irritability, difficulty sleeping, changes in sexual desire, hair loss or unwanted hair growth, spotty darkening on the face, sudden feelings of heat or sweating, leg cramps, painful or difficult urination, back pain, cold or flu symptoms, and swelling, redness, burning, itching or irritation of the vagina. You should contact your doctor if these side effects seem especially persistent or severe.
Other side effects may require immediate medical attention, including: bulging eyes; loss of appetite; stomach pain, swelling or tenderness; yellowing of the skin or eyes; joint pain; movements that are difficult to control; rash or blisters; weakness; hives; hoarseness; difficulty breathing or swallowing; and swelling of the eyes, face, tongue, throat, hands, arms, feet, ankles or lower legs.
In addition, taking estrogen increases the chance of developing endometrial cancer—and the more estrogen you take, the greater the risk. For that reason, many doctors also prescribe a progestin for women who have not reached menopause. While this medication may reduce the risk of endometrial cancer, it may increase the risk of other conditions, including breast cancer; women who take both estrogen and progestin have a higher risk of developing heart attacks, strokes, blood clots in the lungs or legs, breast cancer and dementia. Estrogen may also increase the risk of ovarian or gallbladder cancer; vaginal estrogen that is given to a child may affect the speed and timing of her sexual development, and girls who receive large doses may have slower or stopped growth.