EFFECTS OF HORMONE-REPLACEMENT THERAPY ON HEMOSTATIC FACTORS, LIPID FACTORS, AND ENDOTHELIAL FUNCTION IN WOMEN UNDERGOING SURGICAL MENOPAUSE - IMPLICATIONS FOR PREVENTION OF ATHEROSCLEROSIS

Women with premature menopause are at high risk for vascular complicat ions associated with thrombogenesis and atherogenesis. The use of horm one-replacement therapy (HRT), however, may protect against these comp lications. Hemostatic abnormalities and endothelial function are close ly related to the processes of thrombogenesis and atherogenesis. The p urpose of the study was to evaluate the effects of premature menopause on markers of hemostasis, platelet function, and endothelial function and the effects of starting HRT. This is a prospective longitudinal s tudy of premenopousal women undergoing surgical menopause in whom estr ogen HRT is started. We measured sequential changes in plasma levels o f the hemostatic factors (fibrinogen, fibrin D-dimer, and plasminogen activiator inhibitor [PAI]), markers of platelet function (soluble leu kocyte adhesion molecule P-selectin) and endothelial function (von Wil lebrand factor [vWf], soluble thrombomodulin [sTM], and tissue plasmin ogen activator [TPA]), and serum lipid levels, including lipoprotein A . Twenty-seven premenopausal women (mean age 43.6 +/- 6.5 years) under going hysterectomy and bilateral salpingo-oophrectomy were studied. In the postsurgical menopausal state (visit 2), there was a significant elevation in sTM levels (paired Wilcoxon test, p = 0.008). There was a lso a trend toward higher median soluble P-selectin, PAI, and mean TPA levels and lower vWf levels. After 6 weeks of HRT (visit 3), there wa s a significant reduction in mean vWf (paired Wilcoxon test, p = 0.002 6), sTM (p = 0.039), and TPA levels (p = 0.02) compared with premenopa usal levels. There were no significant changes in plasma fibrinogen, f ibrin D-dimer, and PAI levels at visit 2 or visit 3 compared with prem enopausol levels. There was a significant increase in serum lipoprotei n A (paired Wilcoxon test p = 0.008), cholesterol, and triglyceride le vels after surgical menopause (paired ttest, p < 0.01). Lipoprotein A and cholesterol levels after HRT (visit 3) were not significantly diff erent from prehysterectomy levels, although triglyceride levels were i ncreased further. HRT results in a significant reduction in vWf, sTM, and TPA levels, suggesting beneficial effects on endothelial function and atherogenesis. Although there was a significant increase in serum lipoprotein A and cholesterol levels after surgical menopause, lipopro tein A and cholesterol levels after HRT were not significantly differe nt from presurgery levels. These observations are consistent with the beneficial effects of HRT in cardiovascular hemodynamics and cardiovas cular disease.