Ethynodiol diacetate/mestranol

Both animal experimental work and epidemiological clinical and laboratory research on the effects of endogenous hormones in the human have made it clear that some influence of administered female sex hormones on the risk of certain cancers would be anticipated and this has turned out to be the case. This review focuses on the administration of hormones during pregnancy around the time of the menopause and to prevent pregnancy. In the daughters who were exposed in utero to stilbestrol during the 1950s and 1960s the most important effect is the development of clear cell adenocarcinoma of the vagina or cervix. Few cases of this disease have been reported before puberty but the cumulative risk thereafter up to the age of 24 years is estimated to be between 1.4 and 4/10000 exposed. Much less attention has been paid to the mothers who actually took the stilbestrol than to their daughters but the published data fail to provide any convincing evidence of an increased risk of either breast or reporductive cancer among them. Regarding the administration of hormones around the time of menopause it is well established that unopposed estrogen therapy in menopausal women can cause endometrial cancer. This has been demonstrated in a large number of case control studies reported since 1975. Most of these studies were conducted in the US and most concern the drup Premarin (conjugated equine estrogens). Some cohort studies also have been reported and they largely support the results of the case control studies. There is now little doubt that combined oral contraceptives (OCs) protect against both epithelial ovarian cancer and endometrial cancer. Preliminary findings in the major cohort studies concerned with the longterm effects of OC use also are encouraging. A series of large case control studies conducted during the 1970s showed clearly that there is no general association between oral contraceptive use and breast cancer risk but these large studies included few women with appreciable OC use at an early age and accordingly the publication by Pike et al. in 1981 caused much concern. Pikes study involved 163 women in Los Angeles County in whom breast cancer has been diagnosed at age 32 or less together with a like number of neighborhood controls. Vessey et al. (1982) and the Centers for Disease control subsequently published results which did not support the California findings. Preliminary results from a new case control study conducted in Oxford and in London since 1980 suggest an increased risk of breast cancer in young women who have prolonged OC use before 1st pregnancy. The situation is very confusing and it may be some time before there is a conclusive answer. In a large cohort study conducted in Los Angeles rates of progression from cervical dysplasia to carcinoma in situ were much higher in women using Ovulen than in women using IUDs.