Gender dimorphism following injury: making the connection from bench to bedside

Despite ongoing prevention efforts, injury remains the leading cause of mortality over the first three decades of life in the United States. Those who survive their initial injury continue to be plagued with the development of sepsis and multiple organ failure and their attributable morbidity and mortality. An important and persistent finding has been that males and females respond differently following traumatic injury and hemorrhagic shock. A significant advancement in the experimental understanding of the gender dimorphism in response to trauma-hemorrhage and sepsis has occurred. Experimental evidence for the differential effects of sex hormones on cell-mediated immunity and organ system tolerance of shock continues to expand. Clinical studies, however, have been unable to reproduce these laboratory bench findings consistently. There continues to be a divide between the "bench and bedside" in regard to our understanding of gender-based differences following injury. Relative to controlled animal experiments, predisposing comorbidities, injury characteristics, and a lack of information about the hormone milieu of the trauma patient disallow reproducible results from clinical analyses. Continued clinical research into potential sex hormone-based differences, genetic differences, and the cellular and molecular mechanisms responsible for these gender-based differential responses is required to close this gap. This may ultimately promote therapeutic interventions, which will allow for improved outcomes for males and females in the near future.