The Role of Estrogen in Brain Aging and Alzheimer’s Disease

  • Stanley J. Birge
Part of the Medical Science Symposia Series book series (MSSS, volume 13)


There is a growing appreciation of the role of ovarian hormones as modulators of neuronal function within the central nervous system (CNS). Ovarian failure has long been known to result in reversible changes in mental function, affect, and behavior. More recent epidemiological investigations demonstrate that ovarian failure may result in changes in mental function that can be characterized by an acceleration of brain aging. The clinical expression of these changes are injurious falls, hip fracture, and automobile accidents which can be attributed to a slowing of brain processing of complex sensory information and the generation of a timely response. Estrogen deficiency is also associated with the earlier expression of Alzheimer’s disease. These effects of estrogen can be attributed to the multiple mechanisms whereby estrogens modify brain and neuronal function.


Brain Aging Estrogen Replacement Therapy Estrogen Deficiency Ovarian Failure Early Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Sherwin BB. Affective changes with estrogen and androgen replacement therapy in surgically menopausal women. J Affect Disord 1988;14:177–87.PubMedCrossRefGoogle Scholar
  2. 2.
    Sherwin BB. A prospective one year study of estrogen and progestin in postmenopausal women: effects on clinical symptoms and lipoprotein lipids. Obstet Gynecol 1989;73:759–66.PubMedGoogle Scholar
  3. 3.
    Ditkoff EC, Crary WG, Cristo M, Lobo RA. Estrogen improves psychological function in asymptomatic postmenopausal women. Obstet Gynecol 1991;78:991–95.PubMedGoogle Scholar
  4. 4.
    Gerdes LC, Sonnendecker EW, Polakow ES. Psychological changes effected by estrogen-progestogen and clonidine treatment in climacteric women. Am J Obstet Gynecol 1989;142: 98–104.Google Scholar
  5. 5.
    Phillips S. Sherwin BB. Effects of estrogen on memory function in surgically menopausal women. Psycho Neuroendocrinology 1991;17:485–95.CrossRefGoogle Scholar
  6. 6.
    Bishop J, Simpkins JW. Role of estrogens in peripheral and cerebral glucose utilization in ovariectomized rats. Brain Res Bulletin 1992;36:315–20.CrossRefGoogle Scholar
  7. 7.
    Simpkins JW, Katovich MJ. Hypoglycemia causes hot flushes in animal models. In: Flint M, Kronenberg F, Utian W, editors. Multidisciplinary perspectives on menopause. New York: Annals of the New York Academy of Sciences (vol 592), 1990:433–35.Google Scholar
  8. 8.
    Singh M, Meyer EM, Isaackson PJ, Simpkins JW. The effect of ovariectomy and estradiol-replacement on brain derived neurotrophic factor mRNA expression in brain regions of female Sprague-Dawley rats. Endocrinology 1995;136:2320–24.PubMedCrossRefGoogle Scholar
  9. 9.
    Goodman Y, Bruce AJ, Cheng B, Mattson MP. Estrogens attenuate and cortisone exacerbates excitotoxicity, oxidative injury, and amyloid-β peptide toxicity in hippocampal neurons. J Neurochem 1996;66:1836–44.PubMedCrossRefGoogle Scholar
  10. 10.
    Jorm AF, Korten AE, Henderson AS. The prevalence of dementia: A quantitative integration of the literature. 1987;76:465–79.Google Scholar
  11. 11.
    Paganini-Hill A, Henderson VW. Estrogen deficiency and risk of Alzheimer’s disease in women. Am J Epidemiology 1994;140:256–61.Google Scholar
  12. 12.
    Brenner DE, Kukull WA, Storgachis A, et al. Postmenopausal estrogen replacement therapy and the risk of Alzheimer’s disease: A population-based case-controlled study. Am J Epidemiol 1994;140:262–67.PubMedGoogle Scholar
  13. 13.
    Kawas C, Resnick S, Morrison A, et al. A prospective study of estrogen replacement therapy and the risk of developing Alzheimer’s disease. The Baltimore Longitudinal Study of Aging. Neurology 1997;48:1517–21.Google Scholar
  14. 14.
    Tang M-X, Jacobs D, Stern Y, et al. Effect of estrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet 1996;348:429–32.PubMedCrossRefGoogle Scholar
  15. 15.
    Lerner AJ, Koss E, Debanne SM, et al. Interactions of smoking history with estrogen replacement therapy as protective factors for Alzheimer’s disease. Presentation, 26th Annual Meeting, Society of Neuroscience, Washington, DC, 1996.Google Scholar
  16. 16.
    Caldwell BM. An evaluation of psychological effects of sex hormone administration in aged women. J Gerontology 1954;9:168–74.Google Scholar
  17. 17.
    Kantor HI, Michael CM, Shore H. Estrogen for older women. Am J Obstet Gynecol 1973;116:115–18.PubMedGoogle Scholar
  18. 18.
    Schneider LS, Farlow MR, Henderson VW, Pogoda JM. Effects of estrogen replacement therapy on response to tacrine in patients with Alzheimer’s disease. Neurology 1996, 46:1580–84.PubMedGoogle Scholar
  19. 19.
    Birge SJ. Osteoporosis and hip fracture. Geriatric Medicine Clinics 1993;9:69–86.PubMedGoogle Scholar
  20. 20.
    Halbreich U, Lumley LA, Palter S, et al. Possible acceleration of age effects on cognition following menopause. J Psychiat Res 1995;29:153–63.PubMedCrossRefGoogle Scholar
  21. 21.
    Resnick SM, Metter EJ, Zonderman AB. Estrogen replacement therapy and longitudinal decline in visual memory. Amer Acad Neurology 1997;49:1491–97.Google Scholar

Copyright information

© Kluwer Academic Publishers and Fondazione Giovanni Lorenzini 1999

Authors and Affiliations

  • Stanley J. Birge

There are no affiliations available

Personalised recommendations