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 endothelialfunction differed between hypercholesterolemic postmenopausalwomen (n = 41) and normocholesterolemic postmenopausal women(n = 37), both generally and in terms of effects of long-termhormone replacement therapy (HRT) on endothelial function. Bothmenopause and hypercholesterolemia are associated with endothelialdysfunction 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 weremeasured in serum. FBF during reactive hyperemia as well asserum nitrite/nitrate concentrations were significantly lowerin hypercholesterolemic than normocholesterolemic subjects.Increases in the FBF induced by NTG were similar in the twogroups. HRT significantly increased estradiol, high-densitylipoprotein cholesterol, and serum nitrite/nitrate, while decreasingcirculating angiotensin-converting enzyme activity in both groups.Reduction in total and low-density lipoprotein cholesterol wasseen only in hypercholesterolemic subjects. After 6 months ofHRT, maximal FBF response during reactive hyperemia increasedin both groups. Augmentation of this response was greater inhypercholesterolemic than in normocholesterolemic subjects (maximalFBF, 55.4 ± 11.2 vs. 25.9 ± 11.5%; P < 0.05).Changes in the FBF with NTG were not altered by HRT in eithergroup. Long-term HRT augments endothelial function in forearmresistance artery. This beneficial effect is greater in patientswith hypercholesterolemia.
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