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CLINICAL STUDY

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

^* Cardiology Division and Center for Women’s Health, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA

Manuscript received May 2, 2002; revised manuscript received July 1, 2002, accepted August 19, 2002.

^* Reprint requests and correspondence: Dr. Elsa-Grace V. Giardina, Cardiology Division, Columbia University College of Physicians and Surgeons, 630 West 168th Street, PH 3-346, New York, New York 10032, USA.
evg1{at}columbia.edu

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

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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.

Abbreviations and Acronyms   CEE   conjugated equine estrogen   CRP   C-reactive protein   ERT   estrogen replacement therapy   HDL   high-density lipoprotein cholesterol   HRT   hormone replacement therapy   LDL   low-density lipoprotein cholesterol   MPA   medroxyprogesterone acetate   PAI-1   plasminogen activator inhibitor-1   t-PA   tissue-type plasminogen activator   vWF   von Willebrand factor

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