The influence of biological sex on the metabolic basis of skeletal muscle fatigue in vivo

This study in humans was designed to evaluate: (1) the overall relationships between muscle fatigue and inorganic phosphate (Pi) and hydrogen ions (H+) in women and men, and (2) whether the decline in contractile function for a given change in these intramuscular metabolites differs between sexes (i.e. muscle fatigue sensitivity). Sixteen healthy, young individuals (eight women) performed two consecutive (interspersed by 5 min of rest) intermittent isometric single-leg knee-extensor trials (60 maximal voluntary contractions; 3 s contraction, 2 s relaxation). Throughout both trials, intramuscular quadriceps [Pi] and [H+] were quantified using phosphorus magnetic resonance spectroscopy, and quadriceps twitch force (Q(tw)) was measured using electrical femoral nerve stimulation. The exercise-induced reduction in Q(tw) was greater in men than in women in both trials (both P < 0.048). In both sexes, the Q(tw)-[Pi] relationship was unchanged across trials, while the Q(tw)-[H+] relationship shifted downwards. The decline in Q(tw) for a given increase in [Pi] or [H+] was not different between men and women. The exercise-induced reduction in Q(tw) was strongly associated only with Pi accumulation (r = 0.761, P < 0.001). These results show that, in both sexes, Q(tw) is more consistently related to Pi than to H+, and that the decrease in Q(tw) for a given increase in [Pi] and [H+] does not differ between women and men. This supports that the in vivo metabolic basis of muscle fatigue is similar across sexes, and that differences in the exercise-induced reduction in contractile function relate to the extent of metabolic disturbance, rather than to an inherent fatigue resistance.