BackgroundAlthough hormone replacement therapy has been associated with reduction of cardiovascular events in postmenopausal women, the mechanisms that mediate this apparent benefit are unclear. Because improvement in vaso-motor function may represent one of the beneficial effects of estrogen administration, we investigated the acute effects of physiological levels of estrogen on the vascular responses of estrogen-deficient postmenopausal women.Methods and ResultsThe study included 40 postmeno-pausal women 60±8 years old (mean±SD), 20 of whom had one or more conditions associated with vascular dysfunction (hypertension, hypercholesterolemia, diabetes, or coronary artery disease). The forearm vascular responses to the endo-thelium-dependent vasodilator acetylcholine were studied before and during infusion of 17β-estradiol into the ipsilateral brachial artery. In 31 subjects, the effect of estradiol on the responses to the endothelium-independent vasodilator sodium nitroprusside was also studied. Women with risk factors for vascular dysfunction had significantly reduced vasodilator responses to acetylcholine (P=.01) and to sodium nitroprusside (P<.001) compared with healthy subjects. Intra-arterial infusion of 17β-estradiol increased the forearm venous estradiol concentration from 16±10 to 318±188 pg/mL, levels typical of reproductive-age women at midcycle, but caused no vasodilation. However, estradiol potentiated the forearm vasodilation induced by acetylcholine by 18±30% (P<.001) in women with risk factors for vascular dysfunction and by 14±23% (P=.03) in healthy women. Estradiol also potentiated the forearm vasodilation induced by sodium nitroprusside in women with risk factors for vascular dysfunction by 14±21% (P<.001) but not in healthy women.ConclusionsPhysiological levels of 17,3-estradiol selectively potentiate endothelium-dependent vasodilation in healthy postmenopausal women and potentiate both endothelium-dependent and endothelium-independent vasodilation in post-menopausal women with risk factors for atherosclerosis and evidence of impaired vascular function. These vascular effects may be partly responsible for the long-term benefit of estrogen therapy on cardiovascular events in postmenopausal women.