Brain damage, sex hormones and recovery: a new role for progesterone and estrogen?

Trends Neurosci. 2001 Jul;24(7):386-91. doi: 10.1016/s0166-2236(00)01821-x.


Estrogen and progesterone, long considered for their roles as primary hormones in reproductive and maternal behavior, are now being studied as neuroprotective and neuroregenerative agents in stroke and traumatic brain injuries. Collectively, the hormones reduce the consequences of the injury cascade by enhancing anti-oxidant mechanisms, reducing excitotoxicity (altering glutamate receptor activity, reducing immune inflammation, providing neurotrophic support, stimulating axonal remyelinization), and enhancing synaptogenesis and dendritic arborization. Estrogen seems more effective as a prophylactic treatment in females at risk for cardiac and ischemic brain injury, whereas progesterone appears to be more helpful in the post-injury treatment of both male and female subjects with acute traumatic brain damage. However, a recent clinical trial with estradiol replacement therapy in elderly women that have a history of cerebrovascular disease, showed that this hormone was unable to protect against reoccurrence of ischemia or to reduce the incidence of mortality compared to a placebo.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain Edema / drug therapy*
  • Brain Edema / etiology
  • Brain Injuries / complications
  • Brain Injuries / drug therapy*
  • Estrogens / pharmacology
  • Estrogens / therapeutic use*
  • Female
  • Gonadal Steroid Hormones / pharmacology
  • Gonadal Steroid Hormones / therapeutic use
  • Humans
  • Male
  • Memory / drug effects
  • Memory / physiology
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Progesterone / pharmacology
  • Progesterone / therapeutic use*
  • Recovery of Function / drug effects
  • Recovery of Function / physiology
  • Sex Factors


  • Estrogens
  • Gonadal Steroid Hormones
  • Progesterone