Background: We have previously demonstrated that elevated serum estradiol (E2) at intensive care unit (ICU) admission is associated with death in the critically ill, regardless of sex. However, little is known about how changes in initial E2 during the course of care might signal increasing patient acuity or risk of death. We hypothesized that changes from baseline serum E2 during the course of critical illness are more strongly associated with mortality than a single E2 level at admission. Study Design: A prospective cohort of 1,408 critically ill or injured nonpregnant adult patients requiring ICU care for <48 hours with admission and subsequent E2 levels was studied. Demographics, illness severity, and E2 levels were examined, and the probability of mortality was modeled with multivariate logistic regression. Changes in E2 were examined by both analysis of variance and logistic regression. Results: Overall mortality was 14.1% [95% confidence interval (CI) 12.3% to 16%]. Both admission and subsequent E2 levels were independently associated with mortality [admission E2 odds ratio 1.1 (CI 1.0 to 1.2); repeat estradiol odds ratio 1.3 (CI 1.2 to1.4)], with subsequent values being stronger. Changes in E2 were independently associated with mortality [odds ratio 1.1 (CI 1.0 to 1.16)] and improved regression model performance. The regression model produced an area under the receiver operating characteristic curve of 0.80 (CI 0.77 to 0.83). Conclusions: Although high admission levels of E2 are associated with mortality, changes from baseline E2 in critically ill or injured adults are independently associated with mortality. Future studies of E2 dynamics may yield new indicators of patient acuity and illuminate underlying mechanisms for targeted therapy.
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