Sex dimorphism and sepsis: a novel approach

Experimentally it was recently well established that gender differences lead to an increased susceptibility to sepsis in males.

In a prospective clinical study gender differences were evaluated in patients of a surgical ICU in terms of survival, sex hormones and cytokine response. Fifty-two critically ill patients (19 females and 33 males) were included in this study — there was no difference in the characteristics of patients concerning the age, cause of sepsis and severity of their disease.

Mean age was 55.4 years for females and 53.1 for males. APACHE II score was 17.3 for females and 18.5 for males at entry of the study, MOD-score 9.9 versus 10.8 respectively. Biactivity of TNF and Il-6 were measured for 14 days, as well as 1l-10 (ELISA), total testosteron and 17β-estradiol (RIA).

Though clinical assessment did not reveal any difference, prognosis and outcome of sepsis was significantly different in males and females: MOD-score was always similar in both groups, however, hospital mortality was significantly different with 70% (23/33) in male and 26% (5/19) in female patients (P < 0.01, log-rank test). Evaluation of cytokine response revealed significantly elevated TNF levels on day 10 in males (P < 0.05 Mann-Whitney U-test) while no difference was found for Il-6 levels. Females, however, displayed enhanced Il-10 levels compared to males from day 1 to day 10 which reached significant levels of P< 0.05 on day 3 and day 5. Total testosterone levels were below the normal range for males and estradiol levels were initially increased both in men and postmenopausal women with higher levels for women.

Sex dismorphism, as shown, with a significant better prognosis and outcome of sepsis in women should he considered as a novel therapeutic approach (testosterone receptor blockade) in sepsis.