Time since menopause influences the acute and chronic effect of estrogens on endothelial function.

OBJECTIVE We evaluated whether time since menopause influences the acute and chronic effect of Estradiol (E) on vascular endothelial function. METHODS AND RESULTS We studied flow-mediated dilatation (FMD) in 134 postmenopausal women (PMW) before and after acute and chronic E administration. At baseline FMD was inversely associated to time from menopause (r=-0.67, P<0.001) and age (r=-0.43, P<0.05), in exogenous estrogen naïve but not in previous users. Acute and chronic E improved endothelial function in all women. E administration improved FMD more in women within 5 years since menopause than in those with more than 5 years since menopause (76% and 74% versus 45% and 48%, acute and chronic E, respectively; P<0.05). Among women with more than 5 years since menopause acute and chronic E increased FMD more in previous E users than in nonusers (59% and 63% versus 31% and 38%, acute and chronic E, respectively; P<0.01). Multivariate analysis showed that time from menopause was a predictor of impaired FMD and of its improvement after acute and chronic E. CONCLUSIONS Time from menopause influences FMD in PMW. The acute and chronic effect of E on FMD is time dependent and is reduced by a longer time since menopause.