Estradiol to Androstenedione Ratios Moderate the Relationship between Neurological Injury Severity and Mortality Risk after Severe Traumatic Brain Injury

Early declines in gonadotropin production, despite elevated serum estradiol, among some individuals with severe traumatic brain injury (TBI) suggests amplified systemic aromatization occurs post-injury. Our previous work identifies estradiol (E2) as a potent mortality marker. Androstenedione (A), a metabolic precursor to E2, estrone (E1), and testosterone (T), is a steroid hormone substrate for aromatization that has not been explored previously as a biomarker in TBI. Here, we evaluated serum A, E1, T, and E2 values for 82 subjects with severe TBI. Daily hormone values were calculated, and E2:A and E1:T ratios were generated and then averaged for days 0–3 post-injury. After data inspection, mean E2:A values were categorized as above (high aromatization) and below (low aromatization) the 50th percentile for 30-day mortality assessment using Kaplan-Meier survival analysis and a multivariable Cox proportional hazard model adjusting for age, and Glasgow Coma Scale (GCS) to predict 30-day mortality status. Daily serum T, E1, and E2 were graphed by E2:A category. Serum E1 and E2 significantly differed over time (p