Beyond Binary: Influence of Sex and Gender on Outcome after Traumatic Brain Injury

Traumatic brain injury (TBI) affects millions of individuals each year and is a leading cause of death and disability worldwide. TBI is heterogeneous and outcome is influenced by a combination of factors that include injury location, severity, genetics, and environmental factors. More recently, sex as a biological variable has been incorporated into TBI research, although there is conflicting literature regarding clinical outcomes in males versus females after TBI. We review the current clinical literature investigating sex differences after TBI. We focus our discussion on differences within contemporary gender categories to suggest that binary categories of male and female are not sufficient to guide clinical decisions for neurotrauma. Some studies have considered physiological variables that influence sex such as hormone cycles and stages in males and females pre- and post-TBI. These data suggest that there are phasic differences within male populations and within female populations that influence an individual's outcome after TBI. Finally, we discuss the impact of gender identity and expression on outcome after TBI and highlight the lack of neurotrauma research that includes non-binary individuals. Social constructs regarding gender impact an individual's vulnerability to violence and consequent TBI, including the successful reintegration to society after TBI. We call for incorporation of gender beyond the binary in TBI education, research, and clinical care. Precision medicine necessarily must progress beyond the binary to treat individuals after TBI.