Oral conjugated equine estrogen increases plasma von Willebrand factor in postmenopausal women

We sought to test whether one month of daily oral conjugated equine estrogen (CEE) or transdermal estradiol alters hemostatic factors in postmenopausal subjects.

Estrogen replacement therapy and hormonal replacement therapy (HRT) effect an early increase in cardiovascular events in postmenopausal women. Circulating plasma von Willebrand factor (vWF) antigen is a marker of generalized endothelial dysfunction and atherothrombosis.

Thirty-eight healthy postmenopausal women (average 59 +/- 7 years) were randomized to receive daily oral CEE, 0.625 mg (n = 21); transdermal estradiol, 0.1 mg/day (n = 7); or oral placebo (n = 10) for one month. Blood samples were collected at baseline and after two weeks and four weeks of therapy for measurement of circulating plasma hormones, lipid concentrations, and hemostatic factors.

Oral CEE decreased total cholesterol (p < 0.01) and low-density lipoprotein cholesterol (p < 0.01), although it increased both triglycerides (p < 0.05) and high-density lipoprotein cholesterol (p < 0.01). Transdermal estradiol had no significant effect on lipids. Plasminogen activator inhibitor-1 antigen declined in both oral CEE and transdermal estradiol users, but did not achieve statistical significance. Fibrin D-dimer antigen did not vary significantly in any group. However, oral CEE users had a significant increase in vWF from baseline to four weeks (p < 0.03) and a decrease in tissue-type plasminogen activator antigen from baseline to four weeks (p < 0.004), which was significantly different from the change observed in the transdermal estradiol group (p < 0.05).

These data suggest that the oral CEE-mediated increase in plasma vWF may have clinical relevance given the early atherothrombotic effects of HRT in postmenopausal women.