Effect of menstrual cycle phase and sex on wave reflections and wasted pressure effort in healthy young adults

Early return of arterial wave reflections can increase aortic systolic pressure, left ventricular wasted pressure effort (WPE), and cardiovascular disease risk and mortality. Naturally menstruating premenopausal women experience cyclic fluctuations in female sex hormones that have known cardioprotective effects. Whether these cycle-dependent hormonal fluctuations alter wave reflections and WPE in women or contribute to sex differences is largely unknown. PURPOSE To determine the effect of menstrual cycle phase and biological sex on wave reflection indices and WPE in healthy young adults. HYPOTHESIS Premenopausal women would have favorable changes in wave reflection indices and reduced WPE during high-hormone menstrual cycle phases compared to the low-hormone phase and to men. METHODS Thirteen naturally menstruating women (27±6 yrs; cycle length, 30±6 days) and 7 age-matched men (28±4 yrs), underwent repeated vascular testing. Women were tested during the low-hormone early follicular phase (Visit 1, cycle day 4±2), high-estrogen late follicular phase (Visit 2, cycle day 13±3) and high-progesterone mid-luteal phase (Visit 3, cycle day 23±4). Men’s visits were time-matched to women’s visits. Aortic pressure waves were generated using a generalized transfer function applied to tonometry-derived radial pressure waves. Left ventricular outflow tract diameter and aortic flow velocities were recorded using echocardiography. Pressure-flow alignment and wave separation analyses were performed offline and used to compute maximal forward (Pf) and backward (Pb) pulse wave amplitudes, reflection magnitude (RM=Pb/Pf), reflected wave transit time (RWTT, apparent return of Pb), and WPE. Carotid-femoral pulse wave velocity (PWV) was measured as an index of arterial stiffness. RESULTS Sex by visit interactions were observed for Pb (p=0.02), RM (p=0.04), and WPE (p=0.003). Premenopausal women showed reductions from the early follicular phase to the mid-luteal phase (i.e., Visit 1 vs. Visit 3) in Pb (11±1 vs. 10±1 mmHg, p=0.03), RM (45±7 vs. 42±6%, p=0.05), and WPE (2644 vs. 1984 mmHg·ms, p=0.002) but there were no differences across visits in men (p>0.05 for all). No significant interactions or main effects were observed for Pf, RWTT, or PWV (p>0.05 for all). CONCLUSION Wave reflection indices Pb and RM and left ventricular WPE show favorable reductions in the high-progesterone mid-luteal phase of a natural menstrual cycle. Importantly, these reductions in premenopausal women were not mirrored in men, implicating the role of female sex hormones. Studies of wave reflections and WPE in naturally menstruating premenopausal women should control for menstrual cycle phase. Supported by American Heart Association Grant 826955 and National Institutes of Health grant P20GM113125 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.