The contribution of age and sex hormones to female neuromuscular function across the adult lifespan.

Neuromuscular ageing is characterized by neural and/or skeletal muscle degeneration that decreases maximal force and power. Female neuromuscular ageing occurs earlier in life compared to males, potentially due to sex hormone changes during the menopausal transition. We quantified neuromuscular function in 88 females represented equally over each decade from 18 to 80 years of age and investigated the role of decreased ovarian hormone concentrations following menopause. Neuromuscular assessment included quadriceps maximal voluntary and evoked isometric torque and surface electromyography measurements, plus one-repetition maximum leg press. Voluntary and evoked torques and one-repetition maximum decreased non-linearly with age, with accelerated reductions starting during the fourth decade. An absence of changes in volitional recruitment of existing quadriceps motor units and Ia afferent facilitation of spinal motoneurons suggests that functional decline was largely mediated by impairment in intrinsic peripheral muscle function and/or neuromuscular transmission. Maximal muscle compound action potential amplitude decreased with increasing age for rectus femoris muscle only, indicating increased vulnerability to neuromuscular degeneration compared to vastus lateralis and medialis. In postmenopausal females, some variance was explained by inter-individual differences in quadriceps tissue composition and lifestyle factors, but changes in total or free concentrations of oestradiol, progesterone and/or testosterone were included in all correlations with age-related decreases in isometric voluntary and evoked torques. We demonstrate an accelerated onset of neuromuscular degeneration of peripheral muscular origin around menopause onset associated with changes in sex hormone concentrations. Interventions aimed at mitigating declines in ovarian hormones and their subsequent effects on neuromuscular function after menopause should be further explored. KEY POINTS: Neuromuscular deterioration with age is associated with poor physical function and quality of life in older adults, but female-specific trajectories and mechanisms remain unclear. This study is the first to map neuromuscular function across each decade of the adult lifespan in 88 females from 18 to 80 years old and to examine the potential role of hormonal changes after menopause. We show an accelerated reduction in neuromuscular function, primarily of peripheral muscular origin, that occurs during the fourth decade and coincides with menopause onset. In postmenopausal females, age-related reductions in neuromuscular function can in part be explained by quadriceps lean and intramuscular fat composition, physical activity and protein intake, and sex hormone concentrations. These findings help us better understand the factors that contribute to the loss of neuromuscular function with age in females, enabling the identification of potential therapeutic interventions to prolong female health span.