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Background Ovarian hormones fluctuate across the menstrual cycle (MC) and differ between oral contraceptive users (OC) and naturally menstruating (NM) individuals. Hormones may affect cortical drive to peripheral muscles through excitatory effects of estradiol and inhibitory effects of progesterone on the central nervous system. The impact of hormones on cortical drive is poorly understood. This study aimed to 1) determine the effects of MC phase and OC use on cortical drive and quadriceps performance and 2) determine the relationship between ovarian hormones and these outcomes. Hypothesis Cortical drive will differ between MC phases in NM but not OC participants. Cortical drive will be positively associated with circulating estradiol. Methods Fourteen NM and 11 OC participants completed two time points (High hormone: NM mid-luteal, OC active pill; low hormone: NM early follicular, OC placebo). Hormone concentrations were quantified using enzyme-linked immunosorbent assays. Quadriceps performance (peak torque [PT ISOM ] and rate of torque development [RTD]) was measured via isokinetic dynamometer. Corticospinal excitability and intracortical excitability (short-interval intracortical inhibition [SICI] and intracortical facilitation [ICF]) were assessed using transcranial magnetic stimulation. Linear mixed effects models examined hormone status, phase, and interaction effects. Linear regression determined associations between hormones, cortical drive, and strength. Results There were no significant main effects or interactions for any cortical drive measure. There was a phase by hormone status interaction on RTD100 with greater RTD100 at the high hormone phase compared to the low hormone phase in the NM group but no difference between time points in the OC group. There was a main effect of phase on PT ISOM with greater PT ISOM at the low hormone phase regardless of hormone status. SICI was negatively associated with estradiol. RTD100 was positively associated with progesterone and moderated by hormone status. Conclusions MC phase did not impact cortical drive but did impact quadriceps performance. There were between-phase differences in speed of contraction among NM but not OC participants. Higher progesterone was associated with faster speed of contraction, especially among NM participants. Level of Evidence Level II Key Concepts • Corticospinal and intracortical excitability did not differ by menstrual cycle phase or oral contraceptive use. • Quadriceps rate of torque development was associated with progesterone concentration and varied across the menstrual cycle, suggesting hormone expression influenced RTD (speed of contraction). • The influence of endogenous ovarian hormones on RTD (speed of contraction) differed between oral contraceptive users and naturally menstruating individuals.
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Leung et al. (2026) studied this question.
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