Effects of Testosterone Supplementation on Neurobehavioral Outcomes in Special Operations Military Personnel with Multiple Mild Traumatic Brain Injury

Abstract: Objectives: To investigate differences in neurobehavioral outcomes between testosterone users and non-users in Special Operations military personnel with multiple mild TBI before and after Intensive Evaluation and Training Program (IETP) To investigate indication and benefit of testosterone supplementation in special operations military personnel with multiple mild TBI. Design: Cross-sectional study. Setting: IETP through the Polytrauma Network at the Palo Alto VA Hospital - a three week inpatient program designed to address sequelae of multiple mild TBI and other healthcare needs specifically for active duty Special Operations military personnel. Participants: 55 active duty Special Operations military personnel admitted to IETP with a diagnosis of multiple mild TBI. 6 were on testosterone supplementation at the start of the IETP program and continued it during their stay, the rest are classified as non-users. Interventions: IETP - three weeks of evaluation/treatment by physicians (PM&R +/- various consultants), physical therapy, occupational therapy, speech therapy, Neuropsychology, Rehabilitation Psychology, Headache Psychology, Recreation Therapy. Main outcome measures: Neurobehavioral Outcome Measures, specifically Neurobehavioral Symptom Inventory (NSI), General Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), before and after IETP in testosterone supplementation users vs non-users. Results: Preliminary data suggests a difference in neurobehavioral outcome measures between testosterone users and non-users, with higher mean pre-IETP and post-IETP PHQ-9 and NSI scores and higher mean post-IETP GAD-7 scores. Mean pre-IETP GAD-7 scores were similar between testosterone users and non-users. Conclusions: Our study suggests that testosterone supplementation correlates to worse neurobehavioral outcome scores in active duty Special Operations military personnel, specifically the NSI and PHQ-9, despite improvements in outcome scores during IETP. This study raises speculation that benefits of testosterone supplementation may not outweigh harms/risks. Neuroendocrine dysfunction including hypogonadism is a known complication of mild TBI; the observed correlation found in our study may be explained by increased symptom burden in this subgroup diagnosed with hypogonadism. Further study is needed with larger numbers - the IETP population can provide a suitable population for continued study.

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