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Hormone Replacement Effects on Endothelial Function Measured in the Forearm Resistance Artery in Normocholesterolemic and Hypercholesterolemic Postmenopausal Women

Department of Obstetrics and Gynecology (M.S., M.T., I.K., K.O.) and First Department of Internal Medicine (Y.H., K.N., M.K., K.C.), Faculty of Medicine, Hiroshima University, Hiroshima 734-8551, Japan

Address all correspondence and requests for reprints to: Mitsuhiro Sanada, M.D., Ph.D., Department of Obstetrics and Gynecology, Faculty of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. E-mail: msanada64{at}hotmail.com.

Abstract

We investigated whether forearm resistance artery endothelial function differed between hypercholesterolemic postmenopausal women (n = 41) and normocholesterolemic postmenopausal women (n = 37), both generally and in terms of effects of long-term hormone replacement therapy (HRT) on endothelial function. Both menopause and hypercholesterolemia are associated with endothelial dysfunction and increased coronary risk. Forearm blood flow (FBF) during reactive hyperemia and after sublingual nitroglycerin (NTG) administration was measured by strain-gauge plethysmography. Treated women received conjugated equine estrogen (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) daily for 6 months. Nitrite/nitrate, angiotensin-converting enzyme, and lipids were measured in serum. FBF during reactive hyperemia as well as serum nitrite/nitrate concentrations were significantly lower in hypercholesterolemic than normocholesterolemic subjects. Increases in the FBF induced by NTG were similar in the two groups. HRT significantly increased estradiol, high-density lipoprotein cholesterol, and serum nitrite/nitrate, while decreasing circulating angiotensin-converting enzyme activity in both groups. Reduction in total and low-density lipoprotein cholesterol was seen only in hypercholesterolemic subjects. After 6 months of HRT, maximal FBF response during reactive hyperemia increased in both groups. Augmentation of this response was greater in hypercholesterolemic than in normocholesterolemic subjects (maximal FBF, 55.4 ± 11.2 vs. 25.9 ± 11.5%; P < 0.05). Changes in the FBF with NTG were not altered by HRT in either group. Long-term HRT augments endothelial function in forearm resistance artery. This beneficial effect is greater in patients with hypercholesterolemia.

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