The Effect of the Menstrual Cycle on Intestinal Damage During Running

Introduction: Strenuous exercise results in ischemia that damages the intestinal wall and compromises gut integrity. As the gut influences an athlete’s health, both physiologically and psychologically, exercise induced gut damage (EIGD) may contribute to fatigue, gastrointestinal symptoms, inflammation, and de-motivation, ultimately reducing performance. Estrogen may have protective effects in the gastrointestinal system, however, females make up only 15% of participants in studies pertaining to EIGD and thus are largely absent from the evidence base used to inform recommendations around gut issues in training and performance. The aim of this protocol is to determine relationships between sex hormones and EIGD. Methods: Eight females with a natural menstrual cycle were recruited (age: 29 ± 8 years, weight: 65.4 ± 12.3 kg, VO 2max : 44.2 ± 5.8 ml·kg -1 ·min -1 ). Participants completed an initial maximal oxygen consumption test to determine intensity for the experimental trials which were completed during the early follicular (EF) and late follicular (LF) phases of the menstrual cycle. The order of menstrual phase for each trial was randomized. Hormone status was verified using a three-step method: menstrual cycle tracking throughout the project, urinary luteinizing hormone surge, and confirmatory blood tests. At each trial, participants ran for 60 minutes on a treadmill in a climate controlled chamber in 21°C and 40% relative humidity at a velocity equivalent to 90% of their second ventilatory threshold. Blood samples were taken pre (PRE)- and immediately post-exercise (POST) and analyzed for plasma concentrations of intestinal fatty acid binding protein to determine enterocyte damage, and serum hormonal concentrations (estrogen and progesterone). Gastrointestinal symptoms were assessed using a standardized visual analogue scale. Heart rate, lactate, VO 2 and rating of perceived exertion were recorded at 10 minute intervals throughout each trial. Results: Pre-exercise I-FABP was not different between the high estrogen LF phase compared to the low estrogen EF phase (p = 0.88). Post-exercise I-FABP increased compared to pre-exercise values in both phases (EF median (range) PRE: 416 (217-2246) pg·mL -1 to POST 1164 (392 – 3352) pg·mL -1 , p = 0.008; LF PRE: 444 (215 – 1484) pg·mL -1 to POST: 1012 (353 – 2818) pg·mL -1 , p = 0.05. However, there was no difference in post-exercise I-FABP between the phases, either as absolute values (p = 0.36) or % change (p = 0.54). GI symptoms were most commonly reported in the early follicular phase. Discussion: There is conflicting evidence pertaining to the influence of the menstrual cycle for female athletes, primarily due to poor and inconsistent methodological practices related to determining hormonal status. Understanding menstrual cycle influences in susceptibility to intestinal damage may inform athlete training and competition load with regards to optimizing performance and recovery. This is a novel protocol for the determination of menstrual cycle influences on EIGD. Despite the small sample size, expected patterns of hormones and hypothesized patterns of EIDG were observed, but the data do not provide evidence that the menstrual cycle impacts on the development of EIGD when comparing the high estrogen phase to the low estrogen phase. This research was supported by an Australian Government Research Training Program (RTP) Scholarship This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.