Hormonal Birth Control Is Associated with Altered Gut Microbiota Beta-Diversity in Physically Active Females Across the Menstrual Cycle: A Pilot Trial.

Abstract

Understanding changes to gut microbiota composition in response to hormonal birth control (HBC) may provide insight into the microbial mechanisms underlying the metabolic effects of HBC, for example, altered short-chain fatty acid (SCFA) production. Athletes' unique physiological demands may interact with these microbial mechanisms in distinct ways; however, there is limited research on HBC and gut microbiota diversity and composition across different menstrual cycle phases in physically active females. A pilot cohort of physically active females using HBC (oral contraceptives, hormone-based intrauterine devices, or arm implants) and a control group not using HBC (n=12 per group; 22±2yrs, 24±4kg/m² vs. 22±4yrs, 23±4kg/m²; Ps≥0.496) provided fecal samples alongside self-reported menstrual phase and circulating sex hormones. Alpha diversity (microbial richness and evenness) was assessed using Shannon Index while beta-diversity (microbial composition differences) was analyzed using PERMANOVA based on Bray-Curtis dissimilarity. Circulating estrogen and luteinizing hormone increased from early (days 1-5) to mid-cycle (days 12-17) in both groups (time effect Ps≤0.01), with greater changes in Control (Ps≤0.046) than HBC (Ps≥0.231). While no menstrual phase effect was observed on either diversity measure (Ps≥0.473), beta-diversity differed between Control and HBC groups (P=0.015), reflecting distinct gut microbiota profiles irrespective of menstrual phase. Seven taxa linked to SCFA production were less abundant in the HBC group (unadjusted Ps≤0.046), though significance was lost after adjusting for multiple comparisons. These findings suggest that in physically active females, hormonal contraception influences gut microbial composition, which may have downstream effects on metabolism and performance.