Literature Review of Sex Differences in mTBI

Traumatic brain injury (TBI) remains a significant source of morbidity worldwide and is of particular concern for the military. Scientific literature examining sex differences in TBI is highly contradictory with some reporting better outcomes in men, others reporting better outcomes in women, and others reporting mixed results or no difference. While the exact cause is currently debated, the existence of such differences has important implications for surveillance techniques, treatment options, and management of long-term consequences. As the number of women within the U.S. military ranks increases and with the opening of combat roles to women in 2013, increased awareness of probable sex differences regarding TBI responses will enable better standard of care.

Using the PubMed database, a keyword search using gender, "sex factors", "sex dependent", "gender disparity", TBI, "traumatic brain injury", mTBI (mild TBI), and "cranial trauma" was used to identify articles of interest. Results were filtered for written in the last 5 years, English, and free full text. References of relevant articles were cross-checked for additional publications. Articles familiar to the authors were also included.

We review literature that includes analysis of age as an interaction in TBI, hypothesized mechanisms to explain variations in outcomes between men and women, and the need for inclusion of sex as a criterion in future studies.

Emerging studies underscore the complexity of interpreting sex differences in TBI. The long-held belief that women have a neuroprotective advantage compared to men based on higher levels of sex hormones is being re-evaluated. Past conclusions have relied extensively on clinical studies that include a disproportionate number of men or do not stratify results based on sex. While sex hormones may be neuroprotective, underlying mechanisms are far from clarified. Future TBI studies must include women and gonadal hormone levels should be measured to address potential variables. Given the significant number of TBIs within the military, an improved understanding of TBI pathophysiology and outcomes is important considerations for mission success and servicemember longevity.