Estrogen Improves Endothelium-Dependent, Flow-Mediated Vasodilation in Postmenopausal Women

OBJECTIVE: To assess the effect of estrogen replacement therapy on endothelium-dependent vasodilation in postmenopausal women. DESIGN: Double-blind, placebo-controlled, crossover trial. SETTING: University medical center. PATIENTS: 13 postmenopausal women aged 44 to 69 years (average age, 55 +/- 7 years). INTERVENTION: Patients were randomly assigned to receive placebo, oral estradiol at a dose of 1 mg/d, and oral estradiol at a dose of 2 mg/d. Each treatment phase lasted 9 weeks. MEASUREMENTS: High-resolution ultrasonography was used to measure vascular reactivity in a peripheral conduit vessel, the brachial artery. Endothelium-dependent vasodilation was determined by measuring the change in brachial artery diameter during increases in flow induced by reactive hyperemia. Endothelium-independent vasodilation was measured after sublingual nitroglycerin was administered. RESULTS: Flow-mediated, endothelium-dependent vasodilation of the brachial artery was greater when patients received estradiol (13.5% and 11.6% for 1-mg and 2-mg doses, respectively) than when patients received placebo (6.8%; P < 0.05 for each dose compared with placebo). In contrast, estrogen administration had no effect on endothelium-independent vasodilation as assessed by sublingual nitroglycerin. CONCLUSION: Short-term estrogen replacement therapy improves flow-mediated endothelium-dependent vasodilation in postmenopausal women. This improvement may be mediated by a direct effect of estrogen on vascular function or may be induced through modification of lipoprotein metabolism.