Post-menopausal women are at increased risk for arterial disease and coronary events. However, further information is needed regarding the effects of estrogen and progesterone on the biology of atherosclerosis. The investigators will apply recent concepts regarding vascular biology to examine the effects of sex hormones on the vessel wall in a series of clinical studies. Abnormalities of endothelium- dependent vasodilation occur in atherosclerosis. The investigators hypothesize that estrogen replacement will improve the abnormal endothelium-dependent vasodilation in atherosclerotic arteries of post menopausal women. In particular, the long term effects of both estrogen and estrogen with progesterone on the loss of endothelium- dependent arterial function in atherosclerotic epicardial coronary arteries in postmenopausal women will be examined during sequential cardiac catheterizations. Since vasodilator dysfunction also occurs in limb arteries in patients with coronary artery disease, they will extend these studies to include studies of the mechanisms of action of both estrogen and estrogen with progesterone on vasodilator function in the brachial artery using ultrasonography and plethysmography. They will pharmacologically probe the EDRF (nitric oxide) pathway in the forearm circulation with acetylcholine and 1-monomethyl arginine, the role of vasoactive prostanoids with aspirin and vasoconstrictor responsiveness with phenylephrine and angiotensin II. Since estrogen appears to reduce coronary events in post menopausal women and preliminary evidence shows improvement in endothelium dependent vasodilation, they propose to test the hypothesis that hormone replacement therapy in post menopausal women with obstructive coronary disease and active ischemia can significantly reduce the ischemic burden as measured by ambulatory monitoring. These studies are designed to provide a better understanding of the mechanisms of the beneficial effects of sex hormones on local arterial functions in atherosclerosis in women and to develop knowledge of the use of sex hormones that will provide vascular protection at safe doses in women with coronary artery disease.
| Hamburg, Naomi M; Charbonneau, Francois; Gerhard-Herman, Marie et al. (2004) Comparison of endothelial function in young men and women with a family history of premature coronary artery disease. Am J Cardiol 94:783-5 |
| Seely, E W; Walsh, B W; Gerhard, M D et al. (1999) Estradiol with or without progesterone and ambulatory blood pressure in postmenopausal women. Hypertension 33:1190-4 |
| Gerhard, M; Walsh, B W; Tawakol, A et al. (1998) Estradiol therapy combined with progesterone and endothelium-dependent vasodilation in postmenopausal women. Circulation 98:1158-63 |
