A randomized, placebo-controlled trial of the effects of continuous combined hormone replacement therapy on coagulation and fibrinolytic systems in healthy postmenopausal women

Abstract

Objective To investigate the effects of combined hormone replacement therapy (HRT) on various parameters of coagulation and fibrinolysis that may contribute to increased risk for venous thromboembolic events. Design Prospective, randomized, double-blind, placebo-controlled study. Setting Academic hospital. Patient(s) Sixty-one healthy postmenopausal women with intact uterus. Intervention(s) Patients were randomized to receive continuous combined HRT (estradiol, 2 mg/d, and norethisterone acetate, 1 mg/d) or placebo for 6 months. Main outcome measure(s) Markers of coagulation and fibrinolysis were measured before therapy and after 3 and 6 months of therapy. Result(s) The groups did not differ significantly in levels of prothrombin fragments 1 and 2 and thrombin–antithrombin III complex after 3 and 6 months of therapy. After 6 months of HRT, significant decreases in activity of antithrombin III and protein C and levels of plasminogen activator inhibitor-1 antigen, tissue-type plasminogen activator antigen, and euglobulin clot lysis time and a significant increase in d-dimer level were found compared with placebo. Conclusion(s) Continuous combined HRT for several months produced no net activation of coagulation but improved fibrinolysis in healthy postmenopausal women with no risk factors for venous thromboembolic events.