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In premenopausal women, ovarian steroids are felt to play a role in the prevention of cardiovascular disease. We aimed to assess whether menstrual cycle variations in estrogen can modify the response to ischemia-reperfusion (IR) injury in humans. In an investigator-blinded crossover study, 10 healthy premenopausal women with regular menstrual cycles were studied. They had flow-mediated dilatation (FMD) measured by ultrasound in the radial artery before and after IR (15 min of brachial artery ischemia, 15 min of reperfusion) during both the early and late follicular phases of the menstrual cycle. The order of these visits was not randomized. IR significantly blunted FMD in the early follicular phase (pre-IR: 7.1% ± 1.0%; post-IR: 3.6% ± 1.0%, P = 0.01) when estradiol levels were low (148.4 ± 19.8 pmol/L). Conversely, FMD was preserved after IR during the late follicular phase (pre-IR: 7.2% ± 0.9%; post-IR: 7.0% ± 0.8%, P = NS, P = 0.03 compared with early follicular) when estradiol levels were high (825.7 ± 85.8 pmol/L, P &lt; 0.001 compared with early follicular). There was a significant inverse relationship between estradiol concentration and IR-induced endothelial dysfunction (i.e., change in FMD after IR) (r = 0.59, r 2 = 0.36, P &lt; 0.01). These findings demonstrate, for the first time in humans, a clear relationship between the cyclical changes in serum concentrations of estradiol and the endothelium's response to IR.

Effects of estradiol on measurements of conduit artery endothelial function after ischemia and reperfusion in premenopausal women