Estrogen neuroprotection and the critical period hypothesis

Erin Scott, Quan Guang Zhang, Ruimin Wang, Ratna Vadlamudi, Darrell Brann

Research output: Contribution to journalReview articlepeer-review

107 Scopus citations


17β-Estradiol (estradiol or E2) is implicated as a neuroprotective factor in a variety of neurodegenerative disorders. This review focuses on the mechanisms underlying E2 neuroprotection in cerebral ischemia, as well as emerging evidence from basic science and clinical studies, which suggests that there is a " critical period" for estradiol's beneficial effect in the brain. Potential mechanisms underlying the critical period are discussed, as are the neurological consequences of long-term E2 deprivation (LTED) in animals and in humans after natural menopause or surgical menopause. We also summarize the major clinical trials concerning postmenopausal hormone therapy (HT), comparing their outcomes with respect to cardiovascular and neurological disease and discussing their relevance to the critical period hypothesis. Finally, potential caveats, controversies and future directions for the field are highlighted and discussed throughout the review.

Original languageEnglish (US)
Pages (from-to)85-104
Number of pages20
JournalFrontiers in Neuroendocrinology
Issue number1
StatePublished - Jan 2012


  • Brain
  • Cerebral ischemia
  • Critical period
  • Dementia
  • Estrogen
  • Hormone therapy
  • Menopause
  • Stroke

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems


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