Prospective randomized study of effects of unopposed estrogen replacement therapy on markers of coagulation and inflammation in postmenopausal women

Estrogen replacement therapy decreases the risk of arterial disease while at the same time increases the risk for venous thrombosis. Whether a common mechanism(s) of coagulation and inflammation contributes to both responses is unclear. This study determined simultaneous effects of estrogen replacement therapy on regulators of the direct (extrinsic) pathway for activation of coagulation, coagulation, and the acute phase response. Plasma from 26 postmenopausal women without risk factors for cardiovascular disease was collected before (baseline) and after 3 months of treatment with either conjugated equine estrogen (Premarin, 0.625 mg/d) or placebo. Plasma lipids, tissue factor pathway inhibitor antigen and activity, plasminogen, prothrombin, P-selectin, α₁-protease inhibitor, and C-reactive protein were measured. Estrogen replacement therapy significantly reduced mean concentrations of tissue factor pathway inhibitor (antigen and activity; P < 0.001), which were correlated significantly to decreases in low density lipoprotein (r² = 0.71). Plasminogen and C-reactive protein increased significantly. Other parameters were unchanged. The results of this prospective study suggest that 3 months of estrogen replacement therapy in healthy postmenopausal women decreases low density lipoprotein with simultaneous decreases in tissue factor pathway inhibitor, a major inhibitor of the extrinsic coagulation pathway, and increases C-reactive protein, a component of the acute phase response. Concomitant changes in these parameters may reduce the risk for arterial disease while altering the threshold for thrombotic events.