Both exercise and postmenopausal estrogen therapy augment endothelial function. We hypothesized that their interaction would be additive. The study objectives were to determine in postmenopausal women (1) the effects of an acute bout of exercise on brachial artery endothelium-dependent flow-mediated vasodilation (FMD), (2) whether these responses to exercise are augmented by concurrent estrogen treatment, and (3) whether these 2 interventions, independently or together, achieve FMD values observed in premenopausal women.

In postmenopausal women (n = 13; age 54 ± 2 [mean ± SE] years), FMD was quantified during supine rest and again 60 minutes after treadmill exercise for 45 minutes at 60% V˙o₂max. Subjects were studied twice: before and after 4 weeks of oral estradiol. To obtain reference normal values, FMD was determined concurrently in 14 premenopausal (28 ± 1 years) women under identical basal conditions.

Flow-mediated vasodilation in postmenopausal women, markedly impaired when compared with premenopausal women (5.3% ± 0.5% vs 12.1% ± 1.5%, P < .01), was significantly increased by exercise (to 9.9% ± 0.6%, P < .01). In contrast, after estrogen, FMD was augmented at rest (P < .01) but was not further enhanced after exercise (11.5% ± 0.6% vs 9.9% ± 0.5%, P = .3). Both interventions increased, independently, FMD to values in premenopausal women (P > .05).

In postmenopausal women, both acute exercise and estrogen therapy normalize FMD. However, their effects are not additive, possibly because of redundancy of nitric oxide signaling pathways activated by these 2 interventions. When considered in the context of recent trials with adverse cardiovascular outcomes, these results reinforce the therapeutic potential of exercise as an alternative nonpharmacological intervention to estrogen in postmenopausal women with endothelial dysfunction.