Oral Contraceptives, Concussion History, and Contact-Sport Exposure: Multimodal MRI and Brain Injury Biomarkers in Female Athletes

Neuroimaging and blood-based biomarkers are increasingly utilized to identify long-term effects of concussion and contact-sport exposure (CSE), but female athletes are underrepresented in this work, despite potential sex-related differences. Early research indicates that widely used oral contraceptives (OCs) influence brain structure and function and concussion-related biomarkers. This study investigated whether current oral contraceptive (OC) use moderates associations of concussion history and CSE with magnetic resonance imaging (MRI) measures and brain injury biomarkers in female athletes. Part of a larger cross-sectional study, 68 collegiate-aged female athletes (30 OC users, 38 with no hormonal contraceptive use [NoHC]), completed interviews to retrospectively determine the number of prior concussions (last injury at least 6 months before study enrollment) and years of CSE. Serum glial fibrillary acidic protein, neurofilament light, and total tau levels were measured, along with hippocampal volume, cortical thickness, and Neurite Orientation Dispersion and Density Imaging metrics. Linear regression and Bayesian multilevel modeling tested interactions between OC use and concussion history or CSE on outcomes. Number of prior concussions was negatively associated with hippocampal volumes and cortical thickness. OC use moderated relationships between CSE and cortical thickness, isotropic volume fraction (ISO), and intracellular volume fraction, and between concussion history and orientation dispersion index (ODI). OC users had lower tau levels than the NoHC group. Exploratory models suggested OC pill formulation may moderate associations of concussion history and/or CSE with outcomes and directly affect cortical thickness, ODI, and ISO. These results suggest OC use deserves consideration as an influencing factor in future research and personalized treatment for female athletes.