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Frontiers in Neuroendocrinology 30 (2009) 158–172 Contents lists available at ScienceDirect Frontiers in Neuroendocrinology journal homepage: www.else /locate/yfrne Review Combination treatment with progesterone and vitamin D hormone may be more effective than monotherapy for nervous system injury and disease Milos Cekic, Iqbal Sayeed, Donald G. Stein * Department of Emergency Medicine, Emory University School of Medicine, Atlanta, Georgia, USA a r t i c l e i n f o a b s t r a c t Article history: More than two decades of pre-clinical research and two recent clinical trials have shown that progester- Available online 24 April 2009 one (PROG) and its metabolites exert beneficial effects after traumatic brain injury (TBI) through a number of metabolic and physiological pathways that can reduce damage in many different tissues Keywords: and organ systems. Emerging data on 1,25-dihydroxyvitamin D3 (VDH), itself a steroid hormone, have 1,25-Dihydroxyvitamin D3 begun to provide evidence that, like PROG, it too is neuroprotective, although some of its actions may Combination therapy involve different pathways. Both agents have high safety profiles, act on many different injury and path- Neurosteroids ological mechanisms, and are clinically relevant, easy to administer, and inexpensive. Furthermore, vita- Progesterone min D deficiency i