Essential Role of Estrogen for Improvements in Vascular Endothelial Function With Endurance Exercise in Postmenopausal Women

OBJECTIVE: In contrast to age-matched men, endurance exercise training is not consistently associated with enhanced endothelial function in estrogen-deficient postmenopausal women. We determined whether endurance exercise training improves endothelial function in postmenopausal women treated with estrogen. In a substudy, we determined if oxidative stress is mechanistically linked to endothelial function adaptations to endurance exercise training. PARTICIPANTS AND DESIGN: Brachial artery flow-mediated dilation (FMD) was measured in 36 sedentary, estrogen-deficient postmenopausal women (45-65 y) at study entry (baseline), after 12 weeks of either placebo, oral (1 mg/d) estradiol, or transdermal estradiol (0.05 mg/d) (randomized), and after an additional 12 weeks of continued estradiol or placebo treatment with concurrent endurance exercise training. In subgroups of women, FMD also was measured during the infusion of ascorbic acid at baseline and following estradiol/placebo plus endurance exercise training, and in seven habitually endurance-trained estrogen-deficient controls. RESULTS: FMD increased in the estrogen-treated groups (both P < .01) after 12 weeks and remained unchanged in placebo. FMD further increased following 12 weeks of endurance exercise training in estrogen-treated (both P < .025), but not placebo-treated women (P = .55). In the substudy, baseline FMD was similar between sedentary and endurance-trained controls. Ascorbic acid increased FMD at baseline in sedentary women and endurance-trained controls, and following endurance exercise training in placebo-treated, but not in estrogen-treated women. CONCLUSIONS: Estrogen status appears to play an important modulatory role in improvements in endothelial function with endurance exercise training in postmenopausal women. The restored endurance exercise training adaptation in estrogen-treated postmenopausal women may be related to mitigation of oxidative stress.