Estradiol is associated with mortality in critically ill trauma and surgical patients

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Abstract
Objective: Sexual dimorphism (variation in outcome related to sex) after trauma–hemorrhage and sepsis is well documented in animals, with the pro-estrus state being proinflammatory and associated with a survival advantage. Although some observational studies confirm this pattern in humans, others demonstrate no difference in mortality. Estrogens are important modulators of the inflammatory response and insulin resistance in humans and have been linked to increased mortality during sepsis. Our objective was to determine whether sex hormone levels were associated with outcomes in critically ill surgical patients. Design: Prospective cohort. Patients: A total of 301 adult critically ill or injured surgical patients remaining in the intensive care unit for ≥48 hrs at two academic medical centers. Interventions: None. Measurements: Blood was collected 48 hrs after intensive care unit admission and assayed for sex hormones (estradiol, testosterone, prolactin, and progesterone) and cytokines (tumor necrosis factor-α and interleukin-1, -2, -4, -6, -8, and -10). Demographic and outcome data were also collected. Main Results: Estradiol was significantly higher in nonsurvivors (p < .001). Analysis by quartiles of estradiol demonstrated greater than a three-fold increase in the mortality rate for the highest vs. the lowest estradiol quartiles (29% vs. 8%, p < .001). Estradiol was also higher in nonsurvivors. An estradiol level of 100 pg/mL was associated with an odds ratio for death of 4.60 (95% confidence interval, 1.56–13.0) compared with a reference estradiol level of 45 pg/mL. Conclusions: We conclude that serum estradiol correlates with mortality in critically ill and injured surgical patients and discuss potential mechanisms for this observation.