Sex hormones and related compounds, including oral contraceptives

A 10-year double-blind prospective study was undertaken to evaluate the effects of estrogen replacement therapy (ERT). The sample population consisted of 84 pairs of randomly chosen postmenopausal in-patients, matched for age and diagnosis. The treatment group received high-dose conjugated estrogens, cyclically with progesterone. The controls recieved placebos. Results revealed no statistically significant difference in that incidence of thrombophlebitis, myocardial infarction (MI), or uterine cancer. There was a lower incidence of breast cancer in the treated group. Estrogen-treated patients showed a higher incidence of cholelithiasis. Those in the treated group who began the study with elevated beta/alpha lipoprotein ratios showed a reduction in that ratio over the course of the study, while the controls either maintained or increased their ratios. The low number of cases precludes drawing any real significance from the data on diseases of low frequency. The study excludes only a high incidence of complications from estrogens.

Female residents of King and Ierce Counties in the state of Washington in whom endometrial cancer was diagnosed during 1975--77 were interviewed concerning prior use of oral contraceptives. Their responses were compared with those of a random sample of women from the same population. Women who had taken Oracon (0.1 mg of ethinyl estradiol and 25 mg of dimethisterone) were estimated to have a risk of endometrial cancer 7.3 times that of other women (P = 0.007). This elevation in risk was not seen in users of other sequential preparations. Women who had used combined oral contraceptives had only 50 per cent of the incidence of endometrial cancer of nonusers (P = 0.05), although the protective effect was not evident among those who subsequently took menopausal estrogens for more than two years. These associations suggest that development of neoplasia in the endometrium can be extremely sensitive to hormonal factors: if an oral contraceptive, like Oracon, emphasizes the estrogenic component, promotion of cancer can result; if like combined preparations, the contraceptive emphasizes the progestational component, protection against cancer can result.

We used real-time ultrasonography to study gallbladder kinetics in 11 nonpregnant women, 17 women using steroid contraceptives, and 33 pregnant women. Gallbladder volume was determined after an overnight fast and serially for 90 minutes after a standard liquid meal. After the first trimester of pregnancy, gallbladder volume during fasting and residual volume after contraction were twice as large as in control subjects. The rate of emptying and the percentage emptied were reduced. In early pregnancy the only important abnormality was a 30 per cent decrease in emptying rate. Gallbladder function was not affected by contraceptive steroids. Incomplete empyting of the gallbladder in late pregnancy leaves a large residual volume and may cause retention of cholesterol crystals, a prerequisite for cholesterol-gallstone formation. These findings are consistent with the view that pregnancy increases the risk of cholesterol gallstones. The increased incidence of gallstones associated with contraceptive steroids does not involve abnormal gallbladder kinetics.