In recent years there has been a growing body of clinical and laboratory evidence
demonstrating the neuroprotective effects of estrogen and progesterone after traumatic brain injury
(TBI) and spinal cord injury (SCI). In humans, women have been shown to have a lower incidence of
morbidity and mortality after TBI compared with age-matched men. Similarly, numerous laboratory
studies have demonstrated that estrogen and progesterone administration is associated with a
mortality reduction, improvement in neurological outcomes, and a reduction in neuronal apoptosis
after TBI and SCI. Here, we review the evidence that supports hormone-related neuroprotection and discuss possible
underlying mechanisms. Estrogen and progesterone-mediated neuroprotection are thought to be related to their effects on
hormone receptors, signaling systems, direct antioxidant effects, effects on astrocytes and microglia, modulation of the
inflammatory response, effects on cerebral blood flow and metabolism, and effects on mediating glutamate excitotoxicity.
Future laboratory research is needed to better determine the mechanisms underlying the hormones’ neuroprotective
effects, which will allow for more clinical studies. Furthermore, large randomized clinical control trials are needed to
better assess their role in human neurodegenerative conditions.