Interactions between Gender and Sepsis—Implications for the Future

Abstract

Sex and gender dimorphisms are found in a large variety of diseases, including sepsis and septic shock which are more prevalent in men than in women. Animal models show that the host response to pathogens differs in females and males. This difference is partially explained by sex polarization of the intracellular pathways responding to pathogen–cell receptor interactions. Sex hormones seem to be responsible for this polarization, although other factors, such as chromosomal effects, have yet to be investigated. In brief, females are less susceptible to sepsis and seem to recover more effectively than males. Clinical observations produce more nuanced findings, but men consistently have a higher incidence of sepsis, and some reports also claim higher mortality rates. However, variables other than hormonal differences complicate the interaction between sex and sepsis, including comorbidities as well as social and cultural differences between men and women. Conflicting data have also been reported regarding sepsis-attributable mortality rates among pregnant women, compared with non-pregnant females. We believe that unraveling sex differences in the host response to sepsis and its treatment could be the first step in personalized, phenotype-based management of patients with sepsis and septic shock.

Female Sex and Mortality in Patients with Staphylococcus aureus Bacteremia

“…Firm data for a biological connection between sex differences in clinical outcomes from animal models has been elusive. Previous studies on sepsis have generally supported better outcomes in female patients relative to male . This has been hypothesized to stem from the positive immunomodulatory properties of sex hormones on cell-mediated immune responses and cardiovascular functions in female patients as well as the suppression of the anti-infective response by testosterone in male patients .…”

“…Previous studies on sepsis have generally supported better outcomes in female patients relative to male. 109 This has been hypothesized to stem from the positive immunomodulatory properties of sex hormones on cell-mediated immune responses and cardiovascular functions in female patients 110 , 111 as well as the suppression of the anti-infective response by testosterone in male patients. 112 Even an ongoing immunological advantage in postmenopausal septic women has been reported.…”

Exploring the effects of coronary artery disease as a preexisting comorbidity on mortality in hospitalized septic patients: a retrospective observation study

“…We found no statistically significant difference in the mortality rates for sepsis patients with CAD compared with those without CAD. Past studies have suggested that the prognosis of CAD and sepsis individually differs between male and female patients, [22][23][24][25] which led us to investigate sex as a variable for comparing mortality rates between ASHD CAD and non-ASHD groups. However, there was no disparity found in the mortality rates for male or female patients from either group.…”

Dynamic changes in the migratory microbial components of colon tissue during different periods of sepsis in an LPS-induced rat model

“…However, it is important to acknowledge certain limitations in our study. One limitation is the exclusive use of male rats, which was a decision based on avoiding the potential interference introduced by the estrous cycle in female rats ( Lakbar et al., 2023 ). The study also had an observational nature without interventions to demonstrate the functional impact of microbial translocation.…”