Abstract
Background
Traumatic 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.
Objectives
To investigate how TBI, menopause timing, HRT use, and reproductive history relate to corpus callosum white matter microstructure in female UK Biobank participants.
Design
Cross-sectional analysis of UK Biobank diffusion MRI data using propensity score matching to compare females with TBI to controls.
Methods
We 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.
Results
Females 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
Conclusions
TBI-associated white matter changes in females are related to menopause timing and hormonal exposure, with HRT effects dependent on duration and injury context. These findings highlight the importance of sex- and hormone-specific approaches in TBI research and the need for longitudinal studies to clarify mechanisms and potential interventions.