Systemic estrone production and injury induced sex hormone steroidogenesis after severe traumatic brain injury: a prognostic indicator of TBI-related mortality

Extensive preclinical studies suggest sex steroids are neuroprotective in experimental traumatic brain injury (TBI). Yet, clinical trials involving sex hormone administration have not shown beneficial results, and our observational cohort studies show systemic estradiol (E2) production to be associated with adverse outcomes. Systemic E2 is produced via aromatization of testosterone (T) or reduction of estrone (E1). E1, also produced via aromatization of androstenedione (Andro) and is a marker of T-independent E2 production. We hypothesized E1 would be 1) associated with TBI-related mortality 2) the primary intermediate for E2 production and 3) associated with adipose tissue specific aromatase transcription. We assessed 100 subjects with severe TBI and 8 healthy controls. Serum levels were measured D0-3 post-TBI for key steroidogenic precursors (progesterone), aromatase pathway intermediates (E1, E2, T, Andro) and adipose tissue-specific aromatase transcription factors cortisol, tumor necrosis factor-alpha...