EFFECTS OF HORMONE-REPLACEMENT THERAPY ON FIBRINOLYSIS IN POSTMENOPAUSAL WOMEN

Background Plasma levels of plasminogen-activator inhibitor type 1 (PA I-1), an essential inhibitor of fibrinolysis in humans, increase in wo men after menopause, and this may contribute to the risk of cardiovasc ular disease. We studied the effects of hormone-replacement therapy on PAI-1 levels. Methods In a randomized, crossover study, we investigat ed the effects of oral conjugated estrogen (0.625 mg per day) in 30 po stmenopausal women and transdermal estradiol (0.1 mg per day) in 20 po stmenopausal women, either alone or in combination with medroxyprogest erone acetate (2.5 mg daily) for one month, on plasma PAI-1 antigen le vels. Degradation products of cross-linked fibrin (D-dimer) were measu red in serum as an index of fibrinolysis. Results PAI-1 levels were in versely associated with D-dimer levels at base line (r=-0.540, P=0.002 ). Conjugated estrogen, both alone and in combination with medroxyprog esterone 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), res pectively; there was a significant inverse correlation between pretrea tment 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 ass ociated with increases in D-dimer levels both when conjugated estrogen was given alone (r=-0.572, P=0.001) and when combined hormone therapy was given (r=-0.541, P=0.002). Transdermal estradiol caused no signif icant changes in PAI-1 levels from base-line values. Conclusions Conju gated estrogen, alone or combined with progestin therapy, reduced PAI- 1 levels by approximately 50 percent in postmenopausal women and was a ssociated with enhanced systemic fibrinolysis. These findings may part ly explain the protective effect of hormone-replacement therapy with r espect to coronary artery disease. (C) 1997, Massachusetts Medical Soc iety.