Combination treatment with progesterone and vitamin D hormone may be more effective than monotherapy for nervous system injury and disease

Front Neuroendocrinol. 2009 Jul;30(2):158-72. doi: 10.1016/j.yfrne.2009.04.002. Epub 2009 Apr 24.


More than two decades of pre-clinical research and two recent clinical trials have shown that progesterone (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 and organ systems. Emerging data on 1,25-dihydroxyvitamin D(3) (VDH), itself a steroid hormone, have begun to provide evidence that, like PROG, it too is neuroprotective, although some of its actions may involve different pathways. Both agents have high safety profiles, act on many different injury and pathological mechanisms, and are clinically relevant, easy to administer, and inexpensive. Furthermore, vitamin D deficiency is prevalent in a large segment of the population, especially the elderly and institutionalized, and can significantly affect recovery after CNS injury. The combination of PROG and VDH in pre-clinical and clinical studies is a novel and compelling approach to TBI treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain Injuries / drug therapy
  • Brain Injuries / metabolism
  • Brain Injuries / physiopathology
  • Calcitriol / chemistry
  • Calcitriol / metabolism
  • Calcitriol / therapeutic use*
  • Central Nervous System Diseases / drug therapy*
  • Central Nervous System Diseases / metabolism
  • Central Nervous System Diseases / physiopathology
  • Clinical Trials as Topic
  • Drug Therapy, Combination*
  • Humans
  • Molecular Structure
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / therapeutic use
  • Progesterone / chemistry
  • Progesterone / metabolism
  • Progesterone / therapeutic use*
  • Signal Transduction / physiology
  • Trauma, Nervous System / drug therapy*
  • Trauma, Nervous System / metabolism
  • Trauma, Nervous System / physiopathology
  • Vitamin D Deficiency / drug therapy
  • Vitamin D Deficiency / metabolism
  • Vitamin D Deficiency / physiopathology


  • Neuroprotective Agents
  • Progesterone
  • Calcitriol