Effects Of Contraception And Menstrual Cycle Phase On Extracellular Vesicle Metabolites Following Acute Resistance Exercise

PURPOSE: Recent evidence indicates a slight impact of menstrual cycle status and hormonal contraception (HC) use on exercise performance, with some evidence that HC impacts long term musculoskeletal (MSK) health. Extracellular vesicles (EVs) are lipid bilayer particles that transport a variety of factors such as metabolites. It’s been observed that circulating metabolites are highest in the luteal phase, but no studies have examined the effects of menstrual cycle or HC on EV metabolites following exercise. METHODS: 40 women participated in this study (n = 10/group): Follicular (FOL), Luteal (LUT), oral contraceptive pill (OCP) users, or women with hormonal intrauterine devices (IUD). Menstrual cycle information was determined from self-reports. Blood was drawn before and after a 10x10 bout of weighted plyometric jumps (PlyoPress). Progesterone and 17-β Estradiol were measured and plasma EVs were isolated via Size Exclusion Chromatography (SEC). Untargeted metabolomics was run via LC-HRMS. Differential comparisons generated a list of significant compounds (p < 0.05; Log FC > 2) for pathway analysis (MetaboAnalyst). RESULTS: LUT had higher progesterone than other groups, and greater 17-β Estradiol than FOL. A minimal effect of exercise was found among all women (10 altered metabolites; 1 down, 9 up) however, the effects of exercise varied within groups. FOL women had 26 altered metabolites (12 up; 14 down), women in LUT had 243 (183 up; 60 down). In the HC groups, 60 metabolites were altered in OCP (33 up; 27 down) and 43 in the IUD group (38 up, 5 down). Following pathway analysis, only LUT women had pathways that were predicted to be altered by exercise (60 total). The pathways predicted to be most heavily regulated were glycolysis and the pentose phosphate pathways with glycan regulating pathways also among the top five. CONCLUSIONS: Exercise altered EV metabolites most in LUT women and least in FOL women. Pathway analysis showed a high level of altered pathways predicted in LUT women only, with exercise related pathways among the most prominent. These patterns are in line with evidence indicating circulating metabolite profiles were altered in the luteal phase, potentially due to high estrogen and progesterone. Further evidence is needed to determine how exercise signaling responses are impacted by HC and cycle phase. Supported by: Department of Defense