title: High levels of endogenous estrogens are associated with death in the critically injured adult.
abstract: BACKGROUND
  Sex hormones exhibit predictable changes in their physiologic patterns during critical illness. Endogenous estrogens are elevated in both genders as a result of the peripheral conversion of androgens to estrogens by the aromatase enzyme. Elevated endogenous estrogens have been associated with death in medical and mixed surgical intensive care unit (ICU) patients. Our objective was to determine the relationship between endogenous estrogens and outcomes in critically injured patients.
  
  
  METHODS
  A prospective cohort of injured patients remaining in the ICU for at least 48 hours at two trauma centers was enrolled. Sex hormones (estradiol, progesterone, testosterone, prolactin, and dehydroepiandrosterone-sulfate) were assayed and mortality was assessed. A logistic regression model was used to determine the association between estradiol and death. The area under the receiver operating characteristic (AUROC) curve was used to estimate the accuracy of estradiol in predicting death.
  
  
  RESULTS
  Nine hundred ninety-one patients were enrolled with a 13.4% mortality rate. Despite no detectable difference in mortality among genders, estradiol was significantly elevated in nonsurvivors (16 pg/mL vs. 35 pg/mL, p < 0.001). Estradiol was a marker for injury severity with the most severely injured patients exhibiting the highest levels. The ability of estradiol to predict death (AUROC = 0.65) was comparable with Trauma and Injury Severity Score (AUROC = 0.65) and superior to Injury Severity Score (AUROC = 0.54) in this cohort.
  
  
  CONCLUSIONS
  Serum estradiol is a marker of injury severity and a predictor of death in the critically injured patient, regardless of gender. Whether or not estradiol plays a causal role in outcomes is unclear, but estrogen modulation represents a potential therapy for improving outcomes in critically ill trauma patients.
authors.affiliation: Division of Trauma and Surgical Critical Care, Department of Surgery, Vanderbilt University Medical Center; Nashville, Tennessee, USA. lesly.dossett@vanderbilt.edu
authors.forename: Lesly A
authors.initials: LA
authors.lastname: Dossett
authors.forename: Brian R
authors.initials: BR
authors.lastname: Swenson
authors.forename: Daithi
authors.initials: D
authors.lastname: Heffernan
authors.forename: Hugo
authors.initials: H
authors.lastname: Bonatti
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Metzger
authors.forename: Robert G
authors.initials: RG
authors.lastname: Sawyer
authors.forename: Addison K
authors.initials: AK
authors.lastname: May
mesh_terms: D018806:APACHE; D000328:Adult; D019540:Area Under Curve; D004958:Estradiol / Q000097:blood*; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D015601:Injury Severity Score; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011374:Progesterone / Q000097:blood; D011388:Prolactin / Q000097:blood; D011446:Prospective Studies; D012372:ROC Curve; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000097:blood; D014947:Wounds and Injuries / Q000097:blood* / Q000401:mortality*
chemical_list: D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D011388:Prolactin