Endocrine therapies and hormonal dysfunction after traumatic brain injury: A scoping review

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide, with current management strategies primarily focused on preventing secondary injury rather than modifying disease progression. Post-traumatic endocrine dysfunction has emerged as a significant and potentially treatable contributor to outcomes after TBI.

A scoping review was conducted following PRISMA-ScR guidelines. PubMed, Embase, Scopus, and Web of Science were searched from inception to September 2025 for clinical studies evaluating endocrine dysfunction and endocrine-targeted therapies post-TBI. Eligible studies included clinical trials and observational studies reporting either an endocrine outcome following TBI or an endocrine-targeted intervention with clinical or biochemical outcomes.

Sixty-seven studies met the inclusion criteria. Endocrine dysfunction was common, affecting multiple hormone axes, with growth hormone (GH) deficiency being the most frequently reported deficiency; hypoprolactinemia and hyperprolactinemia were also identified and are increasingly recognized contributors to post-TBI metabolic morbidity. Growth hormone replacement therapy demonstrated improvements in cognitive function, fatigue, mood, and quality of life in several studies; however, its effects on functional outcomes and mortality were inconsistent. Progesterone showed benefit in early-phase trials but failed to demonstrate efficacy in large multicenter randomized controlled trials, an inconsistency that appears closely tied to the timing of treatment initiation after injury. Other therapies, including desmopressin and glucocorticoids, were primarily used for supportive management, with limited evidence of neuroprotective benefit.

Endocrine dysfunction after TBI is prevalent, heterogeneous, and associated with worse clinical outcomes. While endocrine therapies, particularly GH, show promise, their translation into clinical practice is limited by heterogeneity in study design, small sample sizes, and inconsistent findings. Larger, well-designed trials and consensus clinical guidelines are needed to define optimal therapeutic strategies and integrate endocrine care into the optimal management of TBI patients.