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The history of hormone replacement therapy (HRT) dates back to the late 1800s, when animal extracts of ovaries were first used. With the development of synthetic hormones, widespread use in postmenopausal women extended throughout the industrialized world, so that by the late 1900s roughly one-third to one-half of all postmenopausal women in the United States and Europe were taking HRT. Two events changed the course of use of HRT: the association of an increased rate of endometrial carcinoma with estrogen-only HRT and the association of an increased breast cancer rate with combined estrogen and progestin HRT. This review explores the evidence of the effects of HRT on the endometrium and the breast, with emphasis on the pathologic changes.