Menstrual cycle and the protective effects of remote ischemic preconditioning against endothelial ischemia/reperfusion injury: comparison with postmenopausal women

The aim of this study was to determine whether the capacity of remote ischemic preconditioning (IPC) against endothelial ischemia/reperfusion (I/R) injury changes across the menstrual cycle in premenopausal women and to compare IPC responses to postmenopausal women. Thirty-five women were studied (22 premenopausal/13 postmenopausal). Changes in endothelial function were determined during the early follicular vs. the late follicular phase (after positive urine ovulation test; ), vs. the mid-luteal phase (after positive urine progesterone test; ), and vs. estrogen-deficient postmenopausal women; Endothelium-dependent vasodilation was assessed by the forearm blood flow (FBF) to reactive hyperemia with/without I/R injury with remote IPC (3 × 5 min cycles of upper arm ischemia). In the premenopausal women, peak FBF responses during the early follicular phase were blunted 20% ( < 0.0001) with I/R injury (from baseline: 23.4 ± 6.2 to 19.5 ± 4.9 mL/100 mL tissue/min) compared with the late follicular/mid-luteal phases despite IPC. In postmenopausal women, peak FBF was diminished (from: 21.1 ± 5.1 to 17.2 ± 4.4 mL/100 mL tissue/min), and total FBF (area under the curve) was decreased a third (-32%; < 0.001) with I/R injury. Protection from I/R injury was preserved during the late follicular (from baseline: 21.7 ± 5.3 to 24.8 ± 5.9 mL/100 mL tissue/min; = 0.109) and mid-luteal phases (from: 25.1 ± 3.9 to 27.2 ± 5.7 mL/100 mL tissue/min; = 0.267). Reduced estrogen during the early follicular phase and the rise in estrogen associated with ovulation and the mid-luteal phase may contribute to changes in IPC-mediated protection in premenopausal women and shed light on how cardioprotection may change with ovarian hormone deficiency with the menopause transition. The capacity of remote ischemic preconditioning to protect against vascular endothelial ischemia/reperfusion injury varies widely across the phases of the menstrual cycle in healthy premenopausal women. Robust protection was afforded during the late follicular and mid-luteal phases. In contrast, weakened protection was demonstrated during the early follicular phase, with a level of impairment similar to estrogen-deficient postmenopausal women.