Varying Influence of Menstrual Cycle Phase and Hormonal Contraceptive Use on Resistance Exercise‐Induced Circulating Extracellular Vesicle and Metabolite Signalling

Resistance exercise augments circulating extracellular vesicle (EV) and metabolite signalling in manners that assist musculoskeletal and systemic adaptations. Women are often underrepresented in exercise research and recent attention has focused on whether hormonal fluctuations during the menstrual cycle and use of hormonal contraception (HC) impact exercise performance and adaptation. We investigated if menstrual phase (follicular and luteal) or HC usage (oral contraceptive pill and hormonal intrauterine device) impact the EV and metabolite response to exercise. Overall, we observed an exercise-induced response across all four groups for EV microRNAs and circulating metabolites. Women in the follicular phase had baseline differences in the most abundant miRNAs and exercise-relevant miRNAs and had the greatest miRNA response to exercise compared to other groups. Relevant metabolites were observed in EVs, but the overall response to exercise was minimally influenced by group among annotated metabolites. Multi-omic analysis showed potential presence of molecular signatures based on circulating hormone concentrations, but trends were not differentiated enough to suggest clear phenotypic differences. Overall, our data highlights unique miRNA profiles at baseline in follicular phase women but does not support the notion that circulating EV and metabolite responses to exercise are heavily influenced by menstrual cycle phase or HC use. Trial Registration: ClinicalTrials.gov identifier: NCT06972862.