MECHANISMS OF HORMONE THERAPY IN POSTMENOPAUSAL WOMEN

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The use of unopposed estrogen of combined estrogen/progestin therapy for primary and secondary prevention of coronary disease events in post- menopausal women is gaining favor in the United States. Support for this practice is based largely on epidemiological association of a reduction in the risk of death and non-fatal myocardial infarction in populations of women mostly without prior coronary artery disease who took estrogen for a variety of reasons. The effects of adding a progestin to estrogen are less well studied. Because the potential public health impact from treatment of post-menopausal women with hormone replacement therapy for prevention of coronary artery disease events is enormous, it is imperative to establish a fund of knowledge that supports and aids in the interpretation of clinical trials data to help establish the group or groups for whom treatment should be recommended and when it should be initiated. To accomplish these goals we propose: 1. Using non-invasive measurement of vascular reactivity, to quantify the effect on vascular endothelial function of the addition of progesterone to estrogen therapy in post-menopausal women with and without coronary artery disease. 2. To study the effect of various combinations of post-menopausal hormone therapy on the coagulation system. 3. To use accumulated clinical trials databases to study clinical factors that may influence the efficacy of hormone replacement therapy for secondary prevention of coronary artery disease in post-menopausal women. The propose work will provide additional understanding of the mechanism of estrogen action on endothelial function (which is postulated to be the major mechanism of the beneficial effects of estrogen) and the effects of adding progestins to estrogen replacement regimens.