Effects of Female Sex Steroids Administration on Pathophysiologic Mechanisms in Traumatic Brain Injury.

Secondary brain damage following initial brain damage in traumatic brain injury (TBI) is a major cause of adverse outcomes. There are many gaps in TBI research and a lack of therapy to limit debilitating outcomes in TBI or enhance the neurogenesis, despite pre-clinical and clinical research performed in TBI. Females show harmful outcomes against brain damage including TBI less than males, independent of different TBI occurrence. A significant reduction in secondary brain damage and improvement in neurologic outcome post-TBI has been reported following the use of progesterone and estrogen in many experimental studies. Although useful features of sex steroids including progesterone have been identified in TBI clinical trials I and II, clinical trials III have been unsuccessful. This review article focuses on evidence of secondary injury mechanisms and neuroprotective effects of estrogen and progesterone in TBI. Understanding these mechanisms may enable researchers to achieve greater success in TBI clinical studies. It seems that the design of clinical studies should be revised due to translation loss of animal studies to clinical studies. The heterogeneous and complex nature of TBI, the endogenous levels of sex hormones at the time of taking these hormones, the therapeutic window of the drug, the dosage of the drug, the selection of appropriate targets in evaluation, the determination of responsive population, gender and age based on animal studies should be considered in the design of TBI human studies in future.