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Characterization of the Effects of Early Sex-Hormone Environment Following Injury

Principal Investigator: Jason L. Sperry, MD, MPH
Institution: University of Pittsburgh

Although significant advances in the care of the injured patient have occurred over the last decade, those who survived their initial injury continue to be plagued with the development of multiple organ failure, sepsis and their attributable morbid effects.

One important and persistent finding has been that males and females respond differently following traumatic injury and hemorrhagic shock, with a relative protection afforded to females. A large body of literature has evolved attempting to elucidate the mechanisms responsible for these differences; however, a significant divide continues to exist between what experimental animal investigations have revealed and what has been shown clinically in humans.

The ultimate elucidation of the mechanisms responsible for these outcome differences will allow future risk factors and therapeutic targets to be discovered and characterized, having significant potential to improve outcomes in both males and females following injury.

The goal of the study is to further characterize and investigate the early sex-hormone environment following injury and the associations of early estrogen and testosterone levels with the strength of the innate immune response, the coagulation response, resuscitation requirements and clinical outcomes following injury. As few effective interventions exist which alter the morbidity and mortality that inherently follows traumatic injury, investigation into novel mechanisms that may result in a protective effect can provide a route to reduce these sequelae post-injury.

To date, Sperry’s team has enrolled just under 200 patients, obtaining estradiol and testosterone samples in the first six hours post- injury. Early TEG analysis has also been obtained for each patient and multiple organ failure scores, nosocomial infection, and mortality have been prospectively been recorded. The team is beginning batched sex hormone measurements with patient accrual continuing.

Publications

Zolin SJ, Vodovotz Y, Forsythe RM, Rosengart MR, Namas R, Brown JB, Peitzman AP, Billiar TR, Sperry JL. “The early evolving sex hormone environment is associated with significant outcome and inflammatory response differences after injury.” J Trauma Acute Care Surg. 2015 Mar;78(3):451-457; discussion 457-458.
DOI: 10.1097/TA.0000000000000550

Sperry JL, Zolin S, Zuckerbraun BS, Vodovotz Y, Namas R, Neal MD, Ferrell RE, Rosengard MR, Peitzman AB, Billiar TR. X Chromosome-linked IRAK-1 polymorphism is a strong predictor of multiple organ failure and mortality postinjury. Ann Surg. 2014;260(4): 698-703; discussion 703-704.
DOI: 10.1097/SLA.0000000000000918