Gender Dimorphism in Trauma Patients

In recent years, recognition of gender-based differences in patient response to injury/disease has been the subject of much interest (Bone, 1992; Diodato et al., 2001; Verthelyi, 2001; Muller et al., 2002; Orshal and Khalil, 2004; Morales-Montor et al., 2004). Although the findings of some clinical studies do not support the role of gender in the overall outcome of trauma patients, others have provided evidence in support of the suggestion that gender plays a significant role in the outcome of trauma patients (Schroder et al., 1998; Eachempati et al., 1999; Offner et al., 1999; Oberholzer et al., 2000; McGwin et al., 2002; Bowles et al., 2003; George et al., 2003a, 2003b; Gannon et al., 2004). Recently, a retrospective analysis of more than 150,000 blunt or penetrating trauma patients (George et al., 2003a, 2003b) suggested that after blunt trauma, male patients had a significantly higher risk of death as compared with female patients. In addition, these findings suggested that premenopausal women had a survival advantage in blunt trauma patients; however, the opposite pattern prevailed in patients with penetrating trauma (George et al., 2003a, 2003b). Similarly, findings from a prospective analysis of septic patients suggested significantly more deaths in males compared with females (Schroder et al., 1998). Consistent with these findings, another study (Wichmann et al., 2000) concluded that while the overall mortality was not different between males and females after sepsis, only a few female patients required intensive care. In addition, the severity of sepsis/septic shock in females was much lower in intensive care patients. Similar conclusions that the male gender is associated with increased risk of major infection after trauma was drawn in yet another study (Offner et al., 1999). Collectively, these findings suggest that gender plays a role in the outcome of trauma patients. In contrast, some other studies failed to establish the relationship between gender and the outcome of trauma patients (Eachempati et al., 1999; Croce et al., 2002; Bowles et al., 2003; Gannon et al., 2004). For instance, Eachempati et al. (1999) did not find significant differences in mortality between males and females among patients admitted to intensive care units with symptoms of systemic inflammatory response syndrome. Bowles et al. (2003) enrolled 15,170 trauma patients over a 5-year period (1993-1997) and compared outcomes based on gender, age, and severity of injury. They found that age, mechanism, and severity of injury but not gender influenced survival, thus the role of gender in the outcome of trauma patients remains controversial.

Although the cause for the observed differences in clinical studies remains to be established, a series of experimental studies of trauma suggest that the response to injury is different in males and females (Yao et al., 1998; Angele et al., 2000; Kahlke et al., 2000a, 2000b; Samy et al., 2001; Kovacs et al., 2002; Yokoyama et al., 2002; Chaudry et al., 2003). These studies have shown that alterations in immune and cardiovascular functions after trauma-hemorrhage are more severe in mature males, ovariectomized and aged females, whereas both immune and cardiac functions are maintained in proestrus females under those conditions (Yao et al., 1998; Angele et al., 2000; Kahlke et al., 2000a, 2000b; Samy et al., 2001; Kovacs et al., 2002; Yokoyama et al., 2002; Chaudry et al., 2003). Similarly, liver functions after trauma-hemorrhage were found to be depressed in males but were maintained in proestrus females (Remmers et al., 1997, 1998a). Moreover, the survival rate of proestrus females subjected to sepsis after trauma-hemorrhage is significantly higher than age-matched males or ovariec-

tomized females (Zellweger et al., 1997).Thus, the results obtained in experimental model of trauma clearly suggest that the alterations in immune and other organ functions are gender specific. However, the findings from these experimental studies suggest that sex hormone levels and not the gender itself play roles in shaping the host response to an injury such as trauma. Because in patient studies the levels of sex hormones were not determined at the time of injury, it is difficult to ascertain the role of gender in the previously published studies. Therefore, in order to determine the role of gender in post-trauma morbidity and mortality, more patient studies should be planned. These studies should enroll a more homogenous patient population (e.g., age-matched), and the patient outcome should be correlated with the levels of sex hormones rather to the gender of the patients.

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