Estrogen replacement therapy and coagulation: Relationship to lipid and lipoprotein changes

Objective: To examine the relationship of estrogen-induced changes in lipids and lipoproteins with alterations in the coagulation system. Methods: Coagulation and lipid indices were measured in 31 postmenopausal women, ages 40-60 years, after a 3-month course of 0.625-mg conjugated equine estrogen. We analyzed changes in variables from baseline to 3 months using t tests for paired samples or the Wilcoxon matched-pairs signed-rank test. Results: Unopposed estrogen replacement therapy produced statistically significant decreases in antithrombin-III antigen (P = .006) and activity (P = .001) and total protein S (P = .003) and a significant increase in protein C antigen (P = .017). C4b-binding protein also decreased significantly from baseline to 3 months (P < .001). Mean fibrinogen level decreased by 18.2 mg/dL, not a statistically significant change (P = .213). Estrogen produced the expected statistically significant changes in lipids and lipoproteins. Several correlations between changes in lipids and lipoproteins and coagulation indices were statistically significant. Protein C antigen and activity changes correlated directly with high-density lipoprotein cholesterol changes (r = .52, P less than or equal to .005; r = .38, P less than or equal to .05; respectively), and protein C antigen also correlated directly with increases in apoprotein A-I (r = .54, P less than or equal to .005). Triglyceride changes correlated directly with changes in protein C antigen (r = .36, P less than or equal to .05) and activity (I = .49, P less than or equal to .005) and inversely with C4b-binding protein (r = -.58, P less than or equal to .01). Apoprotein B was correlated with free protein S (r = .48, P less than or equal to .01). Conclusions: Although several estrogen-induced changes may decrease atherosclerotic potential and hypercoagulability, others may promote coagulability. These divergent effects may be manipulated pharmacologically by other estrogen compounds or by the addition of various progestins. Copyright (C) 1997 by The American College of Obstetricians and Gynecologists.