Relation of Hormone-Replacement Therapy to Measures of Plasma Fibrinolytic Activity

BACKGROUND: The mechanisms by which replacement hormones may reduce the risk of coronary heart disease are not fully understood. Of specific interest is a potential effect of replacement hormones on plasma fibrinolytic activity, a putative determinant of thrombotic events. METHODS AND RESULTS: We investigated the relation of current use of replacement hormones to three measures of plasma fibrinolytic activity: tissue-type plasminogen activator (TPA) antigen, plasminogen activator inhibitor-1 (PAI-1) antigen, and D-dimer. The sample was composed of 288 women, free of clinical cardiovascular disease, who were selected for a case-control study of atherosclerosis: 142 women with ultrasonographic evidence of carotid intimal-medial thickening (cases) and 146 control subjects. Twenty percent (59 women) reported current use of replacement hormones. TPA antigen and PAI-1 antigen were highly correlated with each other (r = .67), whereas D-dimer correlated only weakly with TPA or PAI-1. Compared with nonusers, current users of replacement hormones had lower mean levels of TPA and PAI-1 antigens, suggesting enhanced fibrinolytic potential. In the entire sample, the multivariate-adjusted geometric mean values of TPA antigen were 6.3 and 7.3 ng/mL among current users and nonusers, respectively (P = .01); the corresponding values for PAI-1 antigen were 6.1 and 7.5 ng/mL (P = .13). These results were generally consistent for both atherosclerosis cases and their control subjects. D-dimer levels were lower in current hormone users than in nonusers, but the difference was not statistically significant (P > .15) in any of the analyses. CONCLUSIONS: The use of replacement hormones appears to be associated with enhancement of endogenous fibrinolytic potential. Enhanced plasma fibrinolytic activity among hormone users may explain, in part, the inverse association between hormone replacement therapy and coronary heart disease.