GENDER DIFFERENCES IN HUMAN SEPSIS

Background: In animal studies, gender differences were related to horm onal and immunologic changes that were associated with an increased su sceptibility to sepsis in males. Objective: In a prospective study, ge nder differences in patients with surgical sepsis were: evaluated in t erms of survival, sex hormones, and proinflammatory as well as anti-in flammatory mediators. Setting: Surgical intensive care unit of a unive rsity hospital. Patients: Fifty-two patients (19 women and 33 men) wit h. surgical sepsis. Measurements and Main Results: In a prospective st udy, tumor necrosis factor ex and interleukin 6 bioactivity and plasma levels of interleukin 10 (using enzyme-linked immunosorbent assay), t otal testosterone, and 17-beta estradiol (using radioimmunoassay) were determined on days 1, 3, 5, 7, 10, and 14 after diagnosis of sepsis. There were no differences in characteristics of patients in age (mean age, 55.4 years for women and 53.1 years for men) or cause and severit y of sepsis (Acute Physiology and Chronic Health Evaluation II score, 17.3 for women and 18.5 for men; multiple organ dysfunction score, 9.9 vs 10.8, respectively). Although no difference could be found ill the multiple organ dysfunction score from day 1 to day 28, the prognosis of sepsis was significantly different in women compared with men. Hosp ital-mortality rate was 70% (23 of 33 patients) in male and 26% (5 of 19) in female patients (P<.008, log-rank test). Bioactivity of tumor n ecrosis factor continuously increased in men after diagnosis of sepsis , with significantly elevated levels on day 10 (P<.05, Mann-Whitney U test with Bonferroni correction),whereas no difference was found for i nterleukin 6 bioactivity. Women displayed enhanced interleukin 10 leve ls compared with men from day 1 to day 10 that reached a significant d ifference on days 3 and 5 (P<.05). Total testosterone levels were belo w the normal range for men, and estradiol levels were initially increa sed in both men and postmenopausal women, with higher levels for women . Conclusions: In this prospective study, gender differences were conf irmed in human sepsis, with a significantly better prognosis for women , which may be related to increased levels of anti-inflammatory mediat ors. The hypothetical different ratio of proinflammatory and anti-infl ammatory mediators may be important for further therapeutic interventi ons in sepsis.