The effects of either moderate alcoholic beverage use or of alcohol abuse in postmenopausal (PMP) women have received scant attention. Because ethanol has been shown in males to increase peripheral conversion of androgens to estrogens as well as to act as an adrenal stimulant, it is possible that alcohol use by PMP women may similarly affect serum levels of androgens and estrogens. Variables which influence estrogen levels in PMP women are important as the risk of such diseases as osteoporosis, cardiovascular disease and cancers of the breast and uterus are reported to be related to estrogenization. Estrogen levels in PMP women reflect adrenal androgen production and the conversion of these androgens to estrogens. The studies to be performed are designed to address specific questions about the effects of both moderate use and abuse of alcoholic beverages on the endocrine status of PMP women. The proposal approaches the questions by using both human and animal studies. The human studies will evaluate the effects of moderate alcohol consumption on levels of estrogens, androgens and gonadotropins in 4 samples of normal PMP women, as well as the effects of chronic alcoholism on endocrine status among PMP women with alcohol-induced cirrhosis as compared to PMP women with other types of liver disease, women with oropharyngeal cancer, and also to moderately drinking normal PMP women. The animal studies will incorporate isocalorically matched triplets of ovariectomized rats fed liquid diets comprising 0, 12 or 36% of total calories as ethanol. The first set of experiments will evaluate the effects of both low and high dose alcohol on hormone levels and bone density using a chronic (daily) exposure model and an intermittent exposure model (4 days of alcohol diet followed by 3 days of control diet, repeatedly). In the second set of experiments, adrenal suppression will be used in both models to assess the contribution of steroid conversion alone to circulating hormone levels. The third animal experiment will assess the effects of shunting of portal venous blood using the partial portal vein ligation model in combination with high dose ethanol administration on hormone levels and femur density of ovariectomized rats. In addition, because consumption of alcoholic beverages entails exposure not only to ethanol but also to beverage congeners, the work of identifying and quantitating estrogenic alcoholic beverage congeners will continue and experiments in ovariectomized rats will examine the endocrine and bone effects of exposure to identified phytoestrogens.
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