An analysis of current literature on sexual dimorphism in response to trauma-hemorrhage revealed conflicting reports on the role of gender in outcomes of trauma patients. In contrast, results obtained from experimental studies clearly support the suggestion that gender plays a significant role in post injury pathogenesis. As discussed in this review, experimental studies suggest that the suppression of immune and cardiac function is severe in males and ovariectomized females; however, both immune and cardiac functions are maintained in proestrus females. Furthermore, findings from a number of studies have shown that the depletion of male sex hormones by castration or by blocking the interaction between male sex steroids and their receptors in males prevented the suppression of both immune and cardiac functions following trauma-hemorrhage. Moreover, administration of estrogen in males and ovariectomized females also prevented the suppression of immune and cardiac functions following trauma-hemorrhage. Thus, these experimental findings collectively suggest that female sex hormones (i.e., estrogen) produce salutary effects following trauma-hemorrhage whereas male sex steroids (i.e. 5α-dihydrotestosterone, 5α-DHT) are suppressive to immune and cardiac functions under those conditions. Such dramatic differences in the outcome of trauma-hemorrhage in proestrus females and males clearly suggest that the prevailing sex hormonal levels at the time of injury play a critical role in shaping the host response to trauma-hemorrhage. While a definitive cause for the conflicting data obtained in the clinical setting remains to be established, the discrepancy could be due to the differences in the hormonal levels at the time of injury. Since there is no information on hormonal status in the clinical studies, it is difficult to ascertain the role of sex hormones in post trauma pathogenesis. Therefore, in order to establish the role of gender in the outcome of trauma patients, more planned studies are needed in which the levels of sex hormones should be measured at the time of hospital admission. Furthermore, more studies, both in the clinical and experimental settings, should be performed to determine the mechanism by which the sex hormones improve immune and organ functions following trauma-hemorrhage. The findings obtained from these studies will help in designing innovative therapeutic approaches for the treatment of trauma patients.
Trauma, organ functions, cytokines, sex steroids
Center for Surgical Research,The University of Alabama at Birmingham, Volker Hall, G094, 1670University Blvd, Birmingham, AL 35294-0019, USA.