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The use of estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluationAll women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinationsIn additionmammography examinations should be scheduled based on patient agerisk factorsand prior mammogram results.

Safety and effectiveness in pediatric patients have not been establishedLarge and repeated doses of estrogen over an extended period of time have been shown to accelerate epiphyseal closureresulting in short adult stature if treatment is initiated before the completion of physiologic puberty in normally developing childrenIn patients in whom bone growth is not completeperiodic monitoring of bone maturation and effects on epiphyseal centers is recommended.

There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogensAdding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasiawhich may be a precursor to endometrial cancerAdequate diagnostic measuresincluding directed or random endometrial sampling when indicatedshould be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

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