Raloxifene, conjugated oestrogen and endothelial function in postmenopausal women

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 = 15) or 150 mg day(-1) (n = 13), conjugated equine oestrogen( CEE) 0.625 mg day(-1) (n = 15), or placebo (n = 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 endothelium-dependent 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.