, Volume 16, Issue 3, pp 649–665 | Cite as

The Role of Estrogen in Brain and Cognitive Aging

  • Jason K. Russell
  • Carrie K. Jones
  • Paul A. NewhouseEmail author


There are 3 common physiological estrogens, of which estradiol (E2) is seen to decline rapidly over the menopausal transition. This decline in E2 has been associated with a number of changes in the brain, including cognitive changes, effects on sleep, and effects on mood. These effects have been demonstrated in both rodent and non-human preclinical models. Furthermore, E2 interactions have been indicated in a number of neuropsychiatric disorders, including Alzheimer’s disease, schizophrenia, and depression. In normal brain aging, there are a number of systems that undergo changes and a number of these show interactions with E2, particularly the cholinergic system, the dopaminergic system, and mitochondrial function. E2 treatment has been shown to ameliorate some of the behavioral and morphological changes seen in preclinical models of menopause; however, in clinical populations, the effects of E2 treatment on cognitive changes after menopause are mixed. The future use of sex hormone treatment will likely focus on personalized or precision medicine for the prevention or treatment of cognitive disturbances during aging, with a better understanding of who may benefit from such treatment.

Key Words

Estrogen menopause aging cognition estradiol critical period 



Preparation of this manuscript was partially supported by the National Institute on Aging R01AG047992, Alzheimer’s Association PCTR-16-383171 to PN, and National Institute on Aging 1R01AG054622 to CJ.

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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2019

Authors and Affiliations

  • Jason K. Russell
    • 1
    • 2
  • Carrie K. Jones
    • 1
    • 2
  • Paul A. Newhouse
    • 3
    • 4
    Email author
  1. 1.Department of PharmacologyVanderbilt UniversityNashvilleUSA
  2. 2.Vanderbilt Center for Neuroscience Drug DiscoveryVanderbilt UniversityNashvilleUSA
  3. 3.Center for Cognitive Medicine, Department of Psychiatry and Behavioral SciencesVanderbilt University Medical CenterNashvilleUSA
  4. 4.Geriatric Research, Education, and Clinical Center (GRECC)Tennessee VA Health SystemsNashvilleUSA

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