The influence of biological sex on the metabolic basis of skeletal muscle fatigue <i>in vivo</i>

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. KEY POINTS: The decline in muscle contractile function during high-intensity exercise (i.e. muscle fatigue) is generally less in women than in men. Sex-related differences in the intrinsic resistance to intramuscular metabolites may explain this divergence. We evaluated (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 intramuscular metabolites differs between sexes. In both sexes, intramuscular Pi was more consistently related to muscle fatigue compared with H⁺. For each metabolite (Pi or H⁺), the decrease in contractile function for a given intramuscular accumulation was similar in women and men. In conclusion, in vivo the metabolic basis of muscle fatigue is similar between sexes. Sex differences in the magnitude of fatigue are therefore probably not due to an intrinsic resistance to intramuscular metabolites.