Abstract
There is growing recognition that traumatic brain injury is a highly variable and complex systemic disorder that is refractory to therapies that target individual mechanisms. It is even more complex in elderly persons, in whom frailty, previous comorbidities, altered metabolism, and a long history of medication use are likely to complicate the secondary effects of brain trauma. Progesterone, one of the few neuroprotective agents that has shown promise for the treatment of acute brain injury, is now in national and international phase 3 multicenter trials. New findings show that vitamin D hormone (VDH) and VDH deficiency in the aging process (and across the developmental spectrum) may interact with progesterone and treatment for traumatic brain injury. In this article we review the use of progesterone and VDH as biologics-based therapies along with recent studies demonstrating that the combination of progesterone and VDH may promote better functional outcomes than either treatment independently.