Estrogens, Aging, and Neurodegenerative Diseases

  • Caleb E. Finch
  • Todd Morgan
  • Irina Rozovsky
Conference paper
Part of the Research and Perspectives in Endocrine Interactions book series (RPEI)


Age is the greatest risk factor in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Indications of a female bias in AD and of a male bias in PD have been often discussed but are not definitive. Moreover, evidence that estrogen replacement may be beneficial for AD and PD is also controversial. An unevaluated factor is how aging and cumulative estrogen exposure may modify brain responses to estradiol. Rodent models show that sustained exposure to estradiol can desensitize certain neuroendocrine responses.


Down Syndrome Estrogen Replacement Therapy Great Life Expectancy Health Initiative Memory Study Postmenopausal Estrogen Replacement Therapy 
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. Benedetti M, Bower J, Maraganore D, McDonnell S, Rocca W (1998) Postmenopausal estrogen replacement therapy and Parkinson’s disease: a population based study in Olmstead County, Minnesota. Mov Disord 13(Suppl 2):51.Google Scholar
  2. Breitner JC, Zandi PP (2003) Effects of estrogen plus progestin on risk of dementia [comment]. JAMA 290:1706–1707; author reply, 1707–1708.CrossRefGoogle Scholar
  3. Brinton RD, Nilsen J (2003) Effects of estrogen plus progestin on risk of dementia [comment]. JAMA 290:1706; author reply, 1707–1708.CrossRefGoogle Scholar
  4. de Rijk MC, Launer LJ, Berger K, Breteler MM, Dartigues JF, Baldereschi M, Fratiglioni L, Lobo A, Martinez-Lage J, Trenkwalder C, Hofman A (2000) Prevalence of Parkinson’s disease in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 54:S21–S23.Google Scholar
  5. Diamond SG, Markham CH, Hoehn MM, McDowell FH, Muenter MD (1990) An examination of male-female differences in progression and mortality of Parkinson’s disease. Neurology 40:763–766.PubMedGoogle Scholar
  6. Dluzen DE (2000) Neuroprotective effects of estrogen upon the nigrostriatal dopaminergic system. J Neurocytol 29:387–399.CrossRefPubMedGoogle Scholar
  7. Finch CE, Felicio LS, Mobbs CV, Nelson JF (1984) Ovarian and steroidal influences on neuroendocrine aging processes in female rodents. Endocrine Rev 5:467–497.Google Scholar
  8. Finch C, Morgan T, Rozovsky I, Xie Z, Weindruch R, Prolla T (2002). Microglia and aging in the brain. In: Streit W (ed) Microglia in the regenerating and degenerating central nervous system. New York: Springer-Verlag pp 275–305.Google Scholar
  9. Gosden RG, Finch CE (2000) Definition and character of reproductive ageing. In: te Velde E, Pearson P, Broekmans F (eds) Female reproductive aging New York: Parthenon Publishing pp 11–26.Google Scholar
  10. Gosden RG, Laing SC, Felicio LS, Nelson JF, Finch CE (1983) Imminent oocyte exhaustion and reduced follicular recruitment mark the transition to acyclicity in aging C57BL/6J mice. Biol Reprod 28:255–260.PubMedGoogle Scholar
  11. Horstink MW, Strijks E, Dluzen DE (2003) Estrogen and Parkinson’s disease. Adv Neurol 91:107–14.PubMedGoogle Scholar
  12. Jellinger KA, Mitter-Ferstl E (2003) The impact of cerebrovascular lesions in Alzheimer disease-a comparative autopsy study. J Neurol 250:1050–1055.CrossRefPubMedGoogle Scholar
  13. Jezierski MK, Sohrabji F (2001) Neurotrophin expression in the reproductively senescent forebrain is refractory to estrogen stimulation. Neurobiol Aging 22:309–219.CrossRefPubMedGoogle Scholar
  14. Kawas CH, Katzman R (1999) Epidemiology of dementia and Alzheimer disease. In: Morris J, Terry R, Katzman R, Bick K, Sisodia S (eds) Alzheimer disease. Philadelphia: Lippincott Williams & Willkins pp 95–116.Google Scholar
  15. Kohama SG, Anderson CP, Osterburg HH, May PC, Finch CE (1989) Oral administration of estradiol to young C57BL/6J mice induces age-like neuroendocrine dysfunctions in the regulation of estrous cycles. Biol Reprod 41:227–232.PubMedGoogle Scholar
  16. Kompoliti K, Comella CL, Jaglin JA, Leurgans S, Raman R, Goetz CG (2000) Menstrual-related changes in motoric function in women with Parkinson’s disease. Neurology 55:1572–1575.PubMedGoogle Scholar
  17. Kukull WA, Higdon R, Bowen JD, McCormick WC, Teri L, Schellenberg GD, van Belle G, Jolley L, Larson EB (2002) Dementia and Alzheimer disease incidence: a prospective cohort study. Arch Neurol 59:1737–1746.CrossRefPubMedGoogle Scholar
  18. Lamberts SW (2003) The endocrinology of gonadal involution: menopause and andropause. Ann Endocrinol 64:77–81.Google Scholar
  19. Lott IT, Head E (2001) Down syndrome and Alzheimer’s disease: a link between development and aging. Ment Retard Dev Disabil Res Rev 7:172–178.CrossRefPubMedGoogle Scholar
  20. Marder K, Tang MX, Alfaro B, Mejia H, Cote L, Jacobs D, Stern Y, Sano M, Mayeux R (1998) Postmenopausal estrogen use and Parkinson’s disease with and without dementia. Neurology 50:1141–1143.PubMedGoogle Scholar
  21. Mayeux R (2003) Epidemiology of neurodegeneration. Annu Rev Neurosci 26:81–104.CrossRefPubMedGoogle Scholar
  22. Mayeux R, Marder K, Cote LJ, Denaro J, Hemenegildo N, Mejia H, Tang MX, Lantigua R, Wilder D, Gurland B (1995) The frequency of idiopathic Parkinson’s disease by age, ethnic group, and sex in northern Manhattan, 1988–1993[erratum appears in Am J Epidemiol 1996 143(5):528]. Am J Epidemiol 142:820–827.PubMedGoogle Scholar
  23. Miller DB, Ali SF, O’Callaghan JP, Laws SC (1998) The impact of gender and estrogen on striatal dopaminergic neurotoxicity. Ann NY Acad Sci 844:153–165.PubMedGoogle Scholar
  24. Morgan TE, Xie Z, Goldsmith S, Yoshida T, Lanzrein AS, Stone D, Rozovsky I, Perry G, Smith MA, Finch CE (1999) The mosaic of brain glial hyperactivity during normal ageing and its attenuation by food restriction. Neuroscience 89:687–699.CrossRefPubMedGoogle Scholar
  25. Murakami K, Nakagawa T, Shozu M, Uchide K, Koike K, Inoue M (1999) Changes with aging of steroidal levels in the cerebrospinal fluid of women. Maturitas 33:71–80.CrossRefPubMedGoogle Scholar
  26. Nelson JF, Felicio LS, Osterburg HH, Finch CE (1992) Differential contributions of ovarian and extraovarian factors to age-related reductions in plasma estradiol and progesterone during the estrous cycle of C57BL/6J mice. Endocrinology 130:805–810.CrossRefPubMedGoogle Scholar
  27. Nichols NR, Day JR, Laping NJ, Johnson SA, Finch CE (1993) GFAP mRNA increases with age in rat and human brain. Neurobiol Aging 14:421–429.CrossRefPubMedGoogle Scholar
  28. O’Neill K, Chen S, Brinton R (2004) Impact of the selective estrogen receptor modulator, raloxifene, on neuronal survival and outgrowth following toxic insults associated with aging and Alzheimer’s disease. Exp Neurol. 185:63–80.CrossRefPubMedGoogle Scholar
  29. Paganini-Hill A, Henderson VW (1994) Estrogen deficiency and risk of Alzheimer’s disease in women. Am J Epidemiol 140:256–261.PubMedGoogle Scholar
  30. Quinn NP, Marsden CD (1986) Menstrual-related fluctuations in Parkinson’s disease. Mov Disord 1:85–87.CrossRefPubMedGoogle Scholar
  31. Ritchie K (1995) Mental status examination of an exceptional case of longevity J. C. aged 118 years. Brit J Psych 166:229–235.Google Scholar
  32. Rostene W, Callier S, D’astous M, Grandbois M, Lesaux M, Bedard P, Di Paolo T, Pelaprat D (2003) Sex steriods in normal and pathological aging: implication in dopaminergic neurodegeneration. Fondation IPSEN Symposium, abstract.Google Scholar
  33. Rozovsky I, Wei M, Stone DJ, Zanjani H, Anderson CP, Morgan TE, Finch CE (2002) Estradiol (E2) enhances neurite outgrowth by repressing glial fibrillary acidic protein expression and reorganizing laminin. Endocrinology 143:636–646.CrossRefPubMedGoogle Scholar
  34. Rozovsky I, Wei M, Morgan TE, Finch CE (2004) Reversible age unpairments in neurite outgrowth by manipulations of astrocytic GFAP. Neurobiol Aging (in press).Google Scholar
  35. Santoro N, Brown JR, Adel T, Skurnick JH (1996) Characterization of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metabol 81:1495–1501.CrossRefGoogle Scholar
  36. Saunders-Pullman R, Gordon-Elliott J, Parides M, Fahn S, Saunders HR, Bressman S (1999) The effect of estrogen replacement on early Parkinson’s disease. Neurology 52:1417–1421.PubMedGoogle Scholar
  37. Schonknecht P, Pantel J, Klinga K, Jensen M, Hartmann T, Salbach B, Schroder J (2001) Reduced cerebrospinal fluid estradiol levels are associated with increased beta-amyloid levels in female patients with Alzheimer’s disease. Neurosci Lett 307:122–124.CrossRefPubMedGoogle Scholar
  38. Schupf N, Kapell D, Nightingale B, Rodriguez A, Tycko B, Mayeux R (1998) Earlier onset of Alzheimer’s disease in men with Down syndrome. Neurology 50:991–995.PubMedGoogle Scholar
  39. Schupf N, Pang D, Patel BN, Silverman W, Schubert R, Lai F, Kline JK, Stern Y, Ferin M, Tycko B, Mayeux R (2003) Onset of dementia is associated with age at menopause in women with Down’s syndrome. Ann Neurol 54:433–438.CrossRefPubMedGoogle Scholar
  40. Sherwin BB (2002) Estrogen and cognitive aging in women. Trends Pharmacol Sci 23:527–34.CrossRefPubMedGoogle Scholar
  41. Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, Hendrix SL, Jones BN, 3rd, Assaf AR, Jackson RD, Kotchen JM, Wassertheil-Smoller S, Wactawski-Wende J, Whims Investigators (2003) Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial [see comment]. JAMA 289:2651–2662.CrossRefPubMedGoogle Scholar
  42. Sparks DL, Martin TA, Gross DR, Hunsaker JC, 3rd (2000) Link between heart disease, cholesterol, and Alzheimer’s disease: a review. Microsc Res Tech 50:287–290.CrossRefPubMedGoogle Scholar
  43. Stone DJ, Rozovsky I, Morgan TE, Anderson CP, Lopez LM, Shick J, Finch CE (2000) Effects of age on gene expression during estrogen-induced synaptic sprouting in the female rat. Exp Neurol 165:46–57.CrossRefPubMedGoogle Scholar
  44. Suthers K, Kim JK, Crimmins E (2003) Life expectancywith cognitive impairment in the older population of the United States. J Gerontol B Psychol Sci Soc Sci. 58:S179–S186.PubMedGoogle Scholar
  45. Tanner C, Hubble J, Chan P (1997) Epidemiology and genetics of Parkinson’s disease. In; Watts R, Koller, W (eds) Movement disorders: neurologic principles and practice.. New York: McGraw-Hill, pp 137–152.Google Scholar
  46. Thulin PC, Filoteo V, Roberts JW, O’Brien SA (1998) Effects of hormone replacement therapy on cognitive and motor function in women with Parkinson’s disease. Neurology 50: A280.Google Scholar
  47. Van Den Eeden SK, Tanner CM, Bernstein AL, Fross RD, Leimpeter A, Bloch DA, Nelson LM (2003) Incidence of Parkinson’s disease: variation by age, gender, and race/ethnicity. Am J Epidemiol 157:1015–1022.CrossRefPubMedGoogle Scholar
  48. vom Saal F, CE F, Nelson J (1994). Natural history of reproductive aging in humans, laboratory rodents, and selected other vertebrates. In: Knobil E (ed) The physiology of reproduction New York: Raven Press, pp 1213–1214Google Scholar
  49. Wise PM (2002) Estrogens and neuroprotection. Trends Endocrinol Metab 13:229–230.CrossRefPubMedGoogle Scholar
  50. Wise PM, Smith MJ, Dubal DB, Wilson ME, Krajnak KM, Rosewell KL (1999) Neuroendocrine influences and repercussions of the menopause. Endocrinol Rev 20:243–248.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • Caleb E. Finch
    • 1
  • Todd Morgan
    • 1
  • Irina Rozovsky
    • 1
  1. 1.Andrus Gerontology Center and Department of Biological SciencesUniversity of Southern CaliforniaLos AngelesUSA

Personalised recommendations