Female Sex and Age-Dependent Survival After Traumatic Shock

BACKGROUND: Whether female sex confers a survival advantage after traumatic shock remains uncertain, and the extent to which this association varies with age may clarify proposed hormonal mechanisms. We examined whether the association between female sex and in-hospital mortality varies across age strata. STUDY DESIGN: We conducted a retrospective cohort study of the National Trauma Data Bank (2019-2023), including adults aged ≥18 years with Injury Severity Score ≥16 and initial systolic blood pressure ≤90 mmHg. The primary endpoint was in-hospital mortality. Multivariable logistic regression evaluated female sex and a sex×age interaction across prespecified strata (18-44, 45-54, and ≥55 years), adjusting for injury severity, mechanism, comorbidity, insurance, race/ethnicity, and severe head, thoracic, and abdominal injury. RESULTS: Among 109,819 patients, female sex was associated with lower in-hospital mortality (adjusted OR 0.86; 95% CI, 0.82-0.89), with significant effect modification by age (χ²[2]=7.69; p=0.0214). Adjusted mortality was lower among females at 18-44 years (15.6% vs 17.0%; difference -1.4 percentage points; p=0.0002), similar at 45-54 years (15.4% vs 16.5%; p=0.1141), and lower at ≥55 years (17.4% vs 20.4%; difference -3.0 percentage points; p<0.0001). The age-dependent association persisted in blunt-only and continuous-age analyses. CONCLUSIONS: Female sex was associated with lower mortality after severe injury with shock, with attenuation in the perimenopausal stratum and the largest advantage among patients aged ≥55 years. This age gradient is inconsistent with a simple endogenous-estrogen explanation. These findings are hypothesis-generating and warrant prospective investigation incorporating hormonal status, biological mediators, and care-limitation practices.