Estrogen--a cause of gynecologic cancer?

For many years before the first case-control studies showing an increased risk of endometrial cancer among menopausal estrogen users were published, a considerable body of circumstantial evidence accumulated suggesting a tumor-promoting role for estrogens in specific target organs. In regard to endometrial cancer, an "estrogen hypothesis" has evolved based on observations such as an increased incidence of endometrial cancer in patients with chronic anovulation and in patients with estrogen-secreting ovarian tumors; development of endometrial cancer in certain estrogen treated animals; and successful treatment of some metastatic endometrial cancer with progesterone. Since 1975, a number of case-control studies have appeared relating estrogen treatment of menopausal women to a rising incidence of endometrial cancer. The same cannot be said, with a few exceptions, of studies of breast and ovarian cancer. An understanding of the physiology of the estrogens, particularly in obese women, aids in understanding the possible role of estrogen in promoting endometrial neoplasia. Although the case for estrogens promoting some forms of endometrial cancer is strong, at the present time it cannot unequivocally be stated that estrogens cause any form of cancer in humans.