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

To examine the relationship of estrogen-induced changes in lipids and lipoproteins with alterations in the coagulation system.

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.

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 < or = .005; r = .38, P < or = .05; respectively), and protein C antigen also correlated directly with increases in apoprotein A-I (r = .54, P < or = .005). Triglyceride changes correlated directly with changes in protein C antigen (r = .36, P < or = .05) and activity (r = .49, P < or = .005) and inversely with C4b-binding protein (r = -.58, P < or = .01). Apoprotein B was correlated with free protein S (r = .48, P < or = .01).

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.