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

ABSTRACT Concentrations of estradiol (E2) and progesterone (P4), the main female sex hormones, exhibit large fluctuations across the menstrual cycle. Due to their receptors throughout the central nervous system, both hormones have the potential to influence motor function by influencing ionotropic and metabotropic inputs to motor pools, which can be estimated through the neural codes extracted from motor unit discharge patterns. To address key methodological limitations in prior menstrual cycle research on motor output, we established the Motor Units and Sex Hormones (MUSH) collaboration. The objective of this multi-site investigation was to determine whether endogenous fluctuations in estradiol and progesterone influence human motor unit activity. We hypothesized that motor unit discharge rates and persistent inward current (PIC)–related contributions to discharge would be greatest during the late follicular phase, when estradiol concentrations were highest. Fifty females completed a comprehensive protocol involving menstrual cycle and ovulation tracking, serum hormone measurement, and high-density surface electromyographic recordings during isometric contractions to quantify motor unit activity in the early follicular, late follicular, and mid luteal phases. After exclusion of 10 females with either atypical hormone concentration profiles or insufficient motor unit yield, 40 remained in the final analysis. There were significant changes in several motor unit discharge variables between menstrual cycle phases and significant associations with hormone concentrations. Increased estradiol was associated with higher peak discharge rates and ascending discharge rate nonlinearity, while increased progesterone was associated with higher peak discharge rates, more discharge rate hysteresis and ascending discharge rate nonlinearity. 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 behavior, but the effects are subtle, highlighting the need for well-powered and methodologically rigorous menstrual cycle research. Graphical Abstract 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 estradiol and progesterone. Discharge rate patterns that provide estimates of neuromodulatory and inhibitory input suggest that estradiol and progesterone 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.