Menstrual Cycle Phase Modulates Central but Not Peripheral Neuromuscular Fatigue in Trained Eumenorrheic Women

<title>Abstract</title> <p> Ovarian-hormone fluctuations across the menstrual cycle may influence neuromuscular function, yet their effect on the central and peripheral contributions to fatigue remains unclear. We examined whether menstrual-cycle phase modulates exercise-induced neuromuscular fatigue in trained eumenorrheic women. Thirteen participants completed, in a randomised counterbalanced order, three sessions timed to the early follicular (EFP), late follicular (LFP) and mid-luteal (MLP) phases, verified by menstrual diaries, urinary ovulation testing and serum oestradiol and progesterone. In each session they performed a sustained isometric knee-extensor contraction at 50% of maximal voluntary contraction (MVC) to task failure; MVC, voluntary activation (VA), potentiated twitch amplitude (Q _tw,pot ), surface electromyography and M-wave amplitude were assessed before and immediately after the task and analysed with linear mixed-effects models. Baseline neuromuscular variables did not differ between phases. Exercise reduced MVC, VA and Q _tw,pot in every phase. The relative loss of MVC and VA depended on phase, whereas the ~45% decline in Q _tw,pot , M-wave amplitude and time to task failure did not. MVC loss was greatest in the MLP and did not differ between the follicular phases after correction, whereas VA loss differed between all three phases, being greatest in the MLP and smallest in the LFP. Because peripheral contractile fatigue was comparable across phases, these findings indicate that menstrual-cycle phase modulates the central, rather than the peripheral, component of neuromuscular fatigue. This pattern is consistent with, though not proof of, an influence of the high-progesterone mid-luteal environment on voluntary neural drive. <bold>Trial registration:</bold> the Pan African Clinical Trial Registry (PACTR202607859511123) Registered 17 July 2026. Retrospectively registered. </p>