Traumatic brain injury associated with altered corpus callosum microstructure in females: Exploring the roles of menopause timing and hormone therapy in UK biobank

BackgroundTraumatic brain injury (TBI) has lasting effects on white matter, yet sex-specific factors such as menopause timing and hormone replacement therapy (HRT) may modulate these outcomes in females.ObjectivesTo investigate how TBI, menopause timing, HRT use, and reproductive history relate to corpus callosum white matter microstructure in female UK Biobank participants.DesignCross-sectional analysis of UK Biobank diffusion MRI data using propensity score matching to compare females with TBI to controls.MethodsWe analyzed diffusion MRI data from females with and without TBI. Corpus callosum fractional anisotropy (FA), mean diffusivity (MD), and isotropic volume fraction (ISOVF) were assessed. TBI effects were examined across pre- and postmenopausal groups, accounting for HRT use, duration, and reproductive factors.ResultsFemales with TBI (n=363) exhibited widespread corpus callosum alterations compared to propensity-matched controls (n=10,128), with reduced FA and elevated MD across multiple sub-regions (all FDR p