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 17beta-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 17beta-estradiol (0.05 mg/d), 17beta-estradiol (0.05 mg/d) + norethindrone acetate (NETA, 0.14 mg/d), and placebo. Flow-mediated dilation (FMD) and response to 400 microg 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.