Age moderates the short-term effects of transdermal 17β-estradiol on endothelium-dependent vascular function in postmenopausal women

Objective - We evaluated age and coronary heart disease ( CHD) as potential moderators of the effects of 17 beta-estradiol on vascular endothelial function in postmenopausal women. Methods and Results - In a double-blind crossover design, 100 postmenopausal women aged 50 to 80 years were randomized to each of 3 transdermal patches, releasing 17 beta-estradiol ( 0.05 mg/d), 17 beta-estradiol ( 0.05 mg/d)+ norethindrone acetate (NETA, 0.14 mg/d), and placebo. Flow-mediated dilation ( FMD) and response to 400 mu g sublingual glyceryl trinitrate (GTN-D) were assessed approximately 18 hours after patch placement. Age, but not CHD, moderated the FMD response to treatment ( P = 0.01). For women in their fifties, the estradiol patch was associated with improved FMD ( 7.69 +/- 4.79%) compared with placebo ( 4.81 +/- 5.97%, P < 0.05), but the estradiol + norethindrone patch response ( 5.81 +/- 4.85%) was not significantly different from placebo. Women in their sixties and seventies showed no alterations in FMD response to either active patch. GTN-D response declined with advancing age ( P < 0.01), with women in their seventies exhibiting blunted GTN-D response compared with younger women. Conclusions - The cardiovascular benefits of natural estrogen supplementation on vascular endothelial function may be dependent on postmenopausal age, with improved vascular function evident only in the early postmenopausal years. Short-term FMD response to estradiol might help stratify individual differences in risks versus benefits of HRT.