Increased arterial wave reflections can increase left ventricular wasted pressure effort (WPE) and cardiovascular disease risk. Naturally menstruating women experience fluctuations in sex hormones with known cardioprotective effects. We sought to determine whether hormonal fluctuations alter arterial hemodynamics or wave reflections, and thereby WPE, or contribute to sex differences. We hypothesized that premenopausal women would have favorable wave reflection changes and reduced WPE during high- versus low-hormone cycle phases and compared with men. We tested 13 women (28 +/- 7 yr) during the early follicular (EF, cycle days 3 +/- 1), late follicular (LF, cycle days 12 +/- 2), and mid-luteal (ML, cycle days 22 +/- 3) phases. Eleven men (28 +/- 3 yr) underwent time-matched visits. Sex hormones and arterial hemodynamics were measured at all visits. Wave reflection indices and WPE were assessed via aortic pressure-flow analyses. We observed sex-by-visit interactions for WPE and total peripheral resistance (TPR; both P < 0.01). Women showed favorable reductions in WPE (EF: 2,758 +/- 966 and LF: 2,489 +/- 1,230 vs. ML: 1,954 +/- 1,085 mmHg<middle dot>ms, both P < 0.05) and TPR (EF: 1,885 +/- 271 vs. ML: 1,699 +/- 255 dyn<middle dot>s<middle dot>cm(-5), P = 0.01) from low- to high-hormone phases. These reductions were not observed in men and were not paralleled in classic wave reflection indices (P > 0.05). Increased estradiol predicted a reduction in TPR (R-2 = 0.45, P < 0.001), whereas TPR, reflected wave amplitude, and timing of wave reflection predicted reductions in WPE (R-2 = 0.71, P < 0.001). These data implicate a role of estradiol on the peripheral vasculature, leading to reduced left ventricular WPE, suggesting a need to consider cycle phases when assessing ventricular load in naturally menstruating women.