Abstract-Currently raloxifene, a selective estrogen receptor modulator, is being investigated as a potential alternative for postmenopausal hormone replacement to prevent osteoporosis and cardiovascular disease. We compared the 2-year effects of raloxifene on a wide range of cardiovascular risk factors with those of placebo and conjugated equine estrogens (CEEs). Analyses were based on 56 hysterectomized but otherwise healthy postmenopausal women aged 54.8Ϯ3.5 (meanϮSD) years who entered this double-blind study and who were randomly assigned to raloxifene hydrochloride 60 mg/d (nϭ15)

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Objectives. To study the long-term effects of raloxifene, a potential designer oestrogen, and oestrogen monotherapy on endothelial function in healthy postmenopausal women. Design. A 2-year double-blind, randomized and placebo-controlled study in an Academic Medical Center. Fifty-six hysterectomized but otherwise healthy postmenopausal women randomly received raloxifene hydrochloride 60 mg day )1 (n ¼ 15) or 150 mg day )1 (n ¼ 13), conjugated equine oestrogen (CEE) 0.625 mg day )1 (n ¼ 15), or placebo (n ¼ 13). Main outcome measures. Endothelial function as estimated from brachial artery flow-mediated, endothelium-dependent vasodilation and nitroglycerine-induced endothelium-independent vasodilation, and plasma levels of the endothelium-derived regulatory proteins, von Willebrand factor (vWF) and endothelin (ET). Results. Raloxifene 60 mg did not significantly affect endothelial function. As compared with placebo, at 6 months of therapy, raloxifene 150 mg and CEE were associated with a mean increase in vWF of 25.5% point (95% CI 3.6-47.3) and 26.6% point (95% CI 6.9-46.3), respectively. At 24 months of therapy, raloxifene 150 mg was associated with a mean decrease in ET of 0.96 pg mL )1 (95% CI )1.57 to )0.36). Raloxifene nor CEE significantly affected endotheliumdependent and/or -independent vasodilation. Conclusions. Our results suggest that long-term therapy with raloxifene or oral CEE does not affect endothelium-dependent vasodilation in healthy postmenopausal women. Raloxifene 150 mg day )1 might have both positive and negative effects on endothelium. The clinical significance of these findings remains to be investigated.

Background: Hyperhomocysteinemia is an independent cardiovascular risk factor, possibly through the induction of endothelial dysfunction. The postmenopausal state is associated with increased plasma homocysteine. We examined whether increased homocysteine is associated with impaired endothelial function. Methods: Sixty-three hysterectomized but otherwise healthy postmenopausal women (54.8 ± 3.5 years) participated in this study. Fasting total plasma homocysteine (tHcy) was measured as free plus protein-bound homocysteine. Endothelial function was assessed by measuring plasma concentrations of the endothelium-derived proteins endothelin (ET), von Willebrand factor (vWF), and plasminogen activator inhibitor type 1 (PAI-1) as well as brachial artery flow-mediated, endothelium-dependent vasodilatation (FMD). Results: Plasma tHcy was 9.6 ± 2.5 μmol/L. After adjustment for possible confounders, a 1 μmol/L increase in tHcy was associated with an increase in ET of 0.08 ng/L (P = 0.045) and an increase in vWF of 4.2% (P = 0.05). No statistically significant association was present between tHcy and PAI-1 or FMD. Conclusions: Increased fasting homocysteine in postmenopausal women may impair some aspects of endothelial function. It is of clinical interest to study whether homocysteine lowering can improve endothelial function and thus cardiovascular morbidity and mortality in postmenopausal women.