Effects of Hormone-Replacement Therapy on Fibrinolysis in Postmenopausal Women

作者：Kwang Kon Koh, Rita Mincemoyer, Minh Bui, György Csákó, Frank Pucino, Victor Guetta, Myron A. Waclawiw, Richard O. Cannon · 发表于：New England Journal of Medicine · 年份：1997 · DOI：10.1056/nejm199703063361002 · 被引用次数：376 · 研究领域：Menopause: Health Impacts and Treatments、Protease and Inhibitor Mechanisms、Phytoestrogen effects and research

BACKGROUND: Plasma levels of plasminogen-activator inhibitor type 1 (PAI-1), an essential inhibitor of fibrinolysis in humans, increase in women after menopause, and this may contribute to the risk of cardiovascular disease. We studied the effects of hormone-replacement therapy on PAI-1 levels. METHODS: In a randomized, crossover study, we investigated the effects of oral conjugated estrogen (0.625 mg per day) in 30 postmenopausal women and transdermal estradiol (0.1 mg per day) in 20 postmenopausal women, either alone or in combination with medroxyprogesterone acetate (2.5 mg daily) for one month, on plasma PAI-1 antigen levels. Degradation products of cross-linked fibrin (D-dimer) were measured in serum as an index of fibrinolysis. RESULTS: PAI-1 levels were inversely associated with D-dimer levels at base line (r= -0.540, P=0.002). Conjugated estrogen, both alone and in combination with medroxyprogesterone acetate, reduced mean (+/-SD) plasma levels of PAI-1 from 32+/-34 ng per milliliter to 14+/-10 ng per milliliter (P<0.001) and from 31+/-29 ng per milliliter to 15+/-11 ng per milliliter (P=0.003), respectively; there was a significant inverse correlation between pretreatment PAI-1 levels and the degree of reduction in these levels during therapy (r= -0.631, P<0.001 for conjugated estrogen; r = -0.507, P=0.004 for combined therapy). The degree of reduction in PAI-1 levels was associated with increases in D-dimer levels both when conjugated estrogen was given alone (r= -0...