Motor unit discharge properties are modestly influenced by menstrual cycle-related fluctuations in sex hormone concentrations.

Oestradiol (E2) and progesterone (P4) fluctuate across the menstrual cycle and potentially influence motor function, which can be estimated from motor unit discharge patterns. To address the methodological limitations of prior menstrual cycle research, we established the motor units and sex hormones (MUSH) collaboration. This multisite investigation aimed to move beyond characterization of motor unit firing across the menstrual cycle and determine whether fluctuations in E2 and P4 influence motor unit activity. We hypothesized that discharge rates and persistent inward current (PIC)-related contributions to discharge would be greatest during the late follicular (LF) phase, when E2 concentrations were highest. Fifty women completed a comprehensive protocol involving menstrual cycle and ovulation tracking, serum hormone measurement and high-density surface electromyographic recordings from the tibialis anterior during isometric contractions to quantify motor unit activity in the early follicular, LF and mid-luteal phases. After 10 women with atypical hormone concentration profiles or insufficient motor unit yield were excluded, 40 remained for analysis. There were significant changes in several motor unit discharge variables between menstrual cycle phases and significant associations with hormone concentrations. Increased E2 was associated with higher peak discharge rates and ascending discharge rate non-linearity, whereas increased P4 was associated with higher peak discharge rates, more discharge rate hysteresis and ascending discharge rate non-linearity. Despite reaching statistical significance, the magnitudes of these effects (i.e. effect sizes) were small. Overall, these findings indicate that fluctuations in sex hormones influence motor unit behaviour, but the effects are subtle, highlighting the need for well-powered and methodologically rigorous menstrual cycle research. KEY POINTS: There are small but detectable differences in motor unit discharge rates between menstrual cycle phases, which are predicted by within-participant fluctuations in oestradiol (E2) and progesterone (P4). Discharge rate patterns that provide estimates of neuromodulatory and inhibitory input suggest that E2 and P4 can influence spinal cord circuitry differently than has previously been documented in the brain, highlighting an understudied aspect of female neurophysiology. Variability in menstrual cycles and associate hormones makes large-scale, rigorous studies especially valuable in female neuromuscular research.