Blood clots are an occasional but serious adverse effect and are dose-related. (The higher the dose, the more likely the clots.) Cigarette smokers are at a higher risk for clots, and, therefore, patients requiring estrogen therapy are strongly encouraged to quit smoking.

Estrogens can promote a buildup of the uterine lining (endometrial hyperplasia) and increase the risk of endometrial carcinoma. At diagnosis, endometrial cancers in estrogen recipients are generally of an earlier stage and a lower grade. Survival is also is better in women exposed to estrogens than in those not exposed to estrogens. The addition of a progestin to estrogen therapy prevents endometrial carcinoma.

Conflicting data exists on the association between estrogens and breast cancer. There may be a small increase in risk. The effect of concomitant progestin therapy on the risk of estrogen-induced breast carcinoma is unclear.

Reference: FDA Prescribing Information

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