Postmenopausal hormone replacement therapy increases coagulation activity and fibrinolysis

Hormone replacement therapy (HRT) appears to be cardioprotective in postmen opausal women; however, concerns exist over its thrombogenic effects. To ad dress the effects of combined HRT on coagulation and fibrinolysis, we have measured circulating markers of these processes in a double-blind placebo-c ontrolled trial. Forty-two healthy postmenopausal women aged 50 to 75 years received continuous combined HRT with 2 mg estradiol+1 mg norethisterone o r placebo for 6 weeks. Hormone profiles were measured at baseline, and lipi d and hemostatic parameters were measured at baseline and after 6 weeks of therapy. Baseline characteristics were similar in the 2 groups. With change from baseline the main outcome measure, HRT increased the markers of coagu lation (prothrombin fragments 1+2, 0.20+/-0.06 versus 0.06+/-0.04 nmol/L, P =0.0005; soluble fibrin, 2.3+/-0.4 versus 0.25+/-0.3 mu g/mL, P=0.0004), re duced plasma fibrinolytic inhibitory activity (plasminogen activator inhibi tor-1, -0.67+/-0.16 versus 0.24+/-0.21 U/mL, P=0.002), and increased fibrin olysis (D-dimer, 24+/-12 versus -6+/-8 ng/mL, P=0.04) compared with placebo . Increases in soluble fibrin and D-dimer were positively correlated (r=0.5 9, P=0.02), but changes in plasminogen activator inhibitor-1 and D-dimer we re unrelated. Although baseline hemostatic and lipid parameters were correl ated, there were no associations between changes in hemostatic markers and lipids after treatment. Short-term oral combined continuous HRT (estradiol and norethisterone) increased thrombin and fibrin generation, reduced plasm a fibrinolytic inhibitory activity, and increased fibrinolysis. Enhanced fi brinolysis was related to increased fibrin generation but not reduced plasm a fibrinolytic inhibitory activity. Coagulation activation may partly expla in the increases in venous thrombosis and cardiovascular events reported wi th the use of combined HRT.