Skip to main content
SpringerLink
Log in

The Impact of Age-Related Ovarian Hormone Loss on Cognitive and Neural Function

  • Chapter
  • First Online:
Behavioral Neurobiology of Aging

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 10))

Abstract

On average, women now live one-third of their lives after menopause. Because menopause has been associated with an elevated risk of dementia, an increasing body of research has studied the effects of reproductive senescence on cognitive function. Compelling evidence from humans, nonhuman primates, and rodents suggests that ovarian sex-steroid hormones can have rapid and profound effects on memory, attention, and executive function, and on regions of the brain that mediate these processes, such as the hippocampus and prefrontal cortex. This chapter will provide an overview of studies in humans, nonhuman primates, and rodents that examine the effects of ovarian hormone loss and hormone replacement on cognitive functions mediated by the hippocampus and prefrontal cortex. For humans and each animal model, we outline the effects of aging on reproductive function, describe how ovarian hormones (primarily estrogens) modulate hippocampal and prefrontal physiology, and discuss the effects of both reproductive aging and hormone treatment on cognitive function. Although this review will show that much has been learned about the effects of reproductive senescence on cognition, many critical questions remain for future investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abe T, Bereczki D, Takahashi Y, Tashiro M, Iwata R, Itoh M (2006) Medial frontal cortex perfusion abnormalities as evaluated by positron emission tomography in women with climacteric symptoms. Menopause 13:891–901

    Article  PubMed  Google Scholar 

  • Adams MM, Shah RA, Janssen WG, Morrison JH (2001) Different modes of hippocampal plasticity in response to estrogen in young and aged female rats. Proc Natl Acad Sci, USA 98:8071–8076

    Article  PubMed  CAS  Google Scholar 

  • Amore M, Di Donato P, Berti A, Palareti A, Chirico C, Papalini A, Zucchini S (2007) Sexual and psychological symptoms in the climacteric years. Maturitas 56:303–311

    Article  PubMed  Google Scholar 

  • Barrett-Connor E, Kritz-Silverstein D (1993) Estrogen replacement therapy and cognitive function in older women. J Am Med Assoc 269:2637–2641

    Article  CAS  Google Scholar 

  • Barrett-Connor E, Laughlin GA (2009) Endogenous and exogenous estrogen, cognitive function, and dementia in postmenopausal women: Evidence from epidemiologic studies and clinical trials. Semin Reprod Med 27:275–282

    Article  PubMed  CAS  Google Scholar 

  • Barrett-Connor E, Goodman-Gruen D, Patay B (1999) Endogenous sex hormones and cognitive function in older men. J Clin Endocrinol Metab 84:3681–3685

    Article  PubMed  CAS  Google Scholar 

  • Bartus RT, Dean RT, Pontecorvo MJ, Flicker C (1985) The cholinergic hypothesis: A historical overview, current perspective, and future directions. Ann NY Acad Sci 444: 332–358

    Article  PubMed  CAS  Google Scholar 

  • Baxter MG, Chiba AA (1999) Cognitive functions of the basal forebrain. Curr Opin Neurobiol 9: 178–183

    Article  PubMed  CAS  Google Scholar 

  • Bellantoni MF, Blackman MR (1996) Menopause and its consequences. In: Schneider EL, Rowe JW (eds) Handbook of the biology of aging. Academic Press, New York, pp 415–430

    Google Scholar 

  • Bellino FL, Wise PM (2003) Nonhuman primate models of menopause workshop. Biol Reprod 68:10–18

    Article  PubMed  CAS  Google Scholar 

  • Berent-Spillson A, Persad C, Love T, Tkaczyk A, Wang H, Reame N, Frey K, Zubieta J, Smith Y (2010) Early menopausal hormone use influences brain regions used for visual working memory. Menopause 17:692–699

    PubMed  Google Scholar 

  • Berger-Sweeney J, Stearns NA, Frick KM, Beard B, Baxter MG (2000) Cholinergic basal forebrain is critical for social transmission of food preferences. Hippocampus 10: 729–738

    Article  PubMed  CAS  Google Scholar 

  • Bi R, Foy MR, Thompson RF, Baudry M (2003) Effects of estrogen, age, and calpain on MAP kinase and NMDA receptors in female rat brain. Neurobiol Aging 24:977–983

    Article  PubMed  CAS  Google Scholar 

  • Bimonte-Nelson HA, Francis KR, Umphlet CD, Granholm A-C (2006) Progesterone reverses the spatial memory enhancements initiated by tonic and cyclic oestrogen therapy in middle-aged ovariectomized female rats. Eur J Neurosci 24:229–242

    Article  PubMed  Google Scholar 

  • Binder E, Schechtman K, Birge S, Williams D (2001) Effects of hormone replacement therapy on cognitive performance in elderly women. Maturitas 38:137–146

    Article  PubMed  CAS  Google Scholar 

  • Boccardi M, Ghidoni R, Govoni S, Testa C, Benussi L, Bonetti M, Binetti G, Frisoni G (2006) Effects of hormone therapy on brain morphology of healthy postmenopausal women: A Voxel-based morphometry study. Menopause 13:584–591

    Article  PubMed  Google Scholar 

  • Brodie AM, Schwarzel WC, Brodie HJ (1976) Studies on the mechanism of estrogen biosynthesis in the rat ovary–I. J Steroid Biochem 7:787–793

    Article  PubMed  CAS  Google Scholar 

  • Choi J, Romeo R, Brake W, Bethea C, Rosenwaks Z, McEwen B (2003) Estradiol increases pre- and post-synaptic proteins in the CA1 region of the hippocampus in female rhesus macaques (Macaca mulatta). Endocrinology 144:4734–4738

    Article  PubMed  CAS  Google Scholar 

  • Daniel JM, Hulst JL, Berbling JL (2006) Estradiol replacement enhances working memory in middle-aged rats when initiated immediately after ovariectomy but not after a long-term period of ovarian hormone deprivation. Endocrinology 147:607–614

    Article  PubMed  CAS  Google Scholar 

  • den Heijer T, Geerlings MI, Hofman A, de Jong FH, Launer LJ, Pols HA, Breteler MM (2003) Higher estrogen levels are not associated with larger hippocampi and better memory performance. Arch Neurol 60:213–220

    Article  Google Scholar 

  • deToledo L, Stoub TR, Wang C (2007) Hippocampal atrophy and disconnection in incipient and mild Alzheimer’s disease. Prog Brain Res 163:741–753

    Article  Google Scholar 

  • Downs JL, Urbanski HF (2006) Neuroendocrine changes in the aging reproductive axis of female rhesus macaques (Macaca mulatta). Biol Reprod 75:539–546

    Article  PubMed  CAS  Google Scholar 

  • Drake EB, Henderson VW, Stanczyk FZ, McCleary CA, Brown WS, Smith CA, Rizzo AA, Murdock GA, Buckwalter JG (2000) Associations between circulating sex steroid hormones and cognition in normal elderly women. Neurology 54:599–603

    Article  PubMed  CAS  Google Scholar 

  • Driscoll I, Sutherland RJ (2005) The aging hippocampus: Navigating between rat and human experiments. Rev Neurosci 16:87–121

    PubMed  CAS  Google Scholar 

  • Duff SJ, Hampson E (2000) A beneficial effect of estrogen on working memory in postmenopausal women taking hormone replacement therapy. Horm Behav 38:262–276

    Article  PubMed  CAS  Google Scholar 

  • Duka T, Tasker R, McGowan JF (2000) The effects of 3 week estrogen hormone replacement on cognition in elderly healthy females. Psychopharmacology 149:129–139

    Article  PubMed  CAS  Google Scholar 

  • Dumitriu D, Rapp PR, McEwen BS, Morrison JH (2010) Estrogen and the aging brain: An elixir for the weary cortical network. Ann N Y Acad Sci 1204:104–112

    Article  PubMed  CAS  Google Scholar 

  • Eberling J, Wu C, Haan M, Mungas D, Buonocore M, Jagust W (2003) Preliminary evidence that estrogen protects against age-related hippocampal atrophy. Neurobiol Aging 24:725–732

    Article  PubMed  CAS  Google Scholar 

  • Eichenbaum H (1997) Declarative memory: Insights from cognitive neurobiology. Annu Rev Psychol 48:547–572

    Article  PubMed  CAS  Google Scholar 

  • Eichenbaum H (2002) The cognitive neuroscience of memory. Oxford University Press, New york, NY

    Book  Google Scholar 

  • Elsabagh S, Hartley DE, File SE (2007) Cognitive function in late versus early postmenopausal stage. Maturitas 56:84–93

    Article  PubMed  Google Scholar 

  • Erickson K, Voss M, Prakash R, Chaddock L, Kramer A (2010) A cross-sectional study of hormone treatment and hippocampal volume in postmenopausal women: Evidence for a limited window of opportunity. Neuropsychology 24:68–76

    Article  PubMed  Google Scholar 

  • Espeland MA, Rapp SR, Shumaker SA, Brunner R, Manson JE, Sherwin BB, Hsia J, Margolis KL, Hogan PE, Wallace R, Dailey M, Freeman R, Hays J (2004) Conjugated equine estrogens and global cognitive function in postmenopausal women: Women’s Health Initiative Memory Study. J Am Med Assoc 291:2959–2968

    Article  CAS  Google Scholar 

  • Fan L, Orr PT, Zhao Z, Chambers CH, Lewis MC, Frick KM (2010) Estradiol-induced object memory consolidation in middle-aged female mice requires dorsal hippocampal extracellular signal-regulated kinase and phosphatidylinositol 3-kinase activation. J Neurosci 30:4390–4400

    Article  PubMed  CAS  Google Scholar 

  • Farkash Y, Timberg R, Orly J (1986) Preparation of antiserum to rat cytochrome P-450 cholesterol side chain cleavage, and its use for ultrastructural localization of the immunoreactive enzyme by protein A-gold technique. Endocrinology 118:1353–1365

    Article  PubMed  CAS  Google Scholar 

  • Fernandez SM, Frick KM (2004) Chronic oral estrogen affects memory and neurochemistry in middle-aged female mice. Behav Neurosci 118:1340–1351

    Article  PubMed  CAS  Google Scholar 

  • Fernandez SM, Lewis MC, Pechenino AS, Harburger LL, Orr PT, Gresack JE, Schafe GE, Frick KM (2008) Estradiol-induced enhancement of object memory consolidation involves hippocampal ERK activation and membrane-bound estrogen receptors. J Neurosci 28:8660–8667

    Article  PubMed  CAS  Google Scholar 

  • Foster TC (2005) Interaction of rapid signal transduction cascades and gene expression in mediating estrogen effects on memory over the lifespan. Front Neuroendocrinol 26:51–64

    Article  PubMed  CAS  Google Scholar 

  • Foy MR, Xu J, Xie X, Brinton RD, Thompson RF, Berger TW (1999) 17ß-estradiol enhances NMDA receptor-mediated EPSPs and long-term potentiation. J Neurophysiol 81:925–929

    PubMed  CAS  Google Scholar 

  • Frick KM (2009) Estrogens and age-related memory decline in rodents: What have we learned and where do we go from here? Horm Behav 55:2–23

    Article  PubMed  CAS  Google Scholar 

  • Frick KM, Burlingame LA, Arters JA, Berger-Sweeney J (2000) Reference memory, anxiety, and estrous cyclicity in C57BL/6NIA mice are affected by age and sex. Neuroscience 95:293–307

    Article  PubMed  CAS  Google Scholar 

  • Frick KM, Fernandez SM, Bulinski SC (2002) Estrogen replacement improves spatial reference memory and increases hippocampal synaptophysin in aged female mice. Neuroscience 115:547–558

    Article  PubMed  CAS  Google Scholar 

  • Frick KM, Fernandez SM, Harburger LL (2010) A new approach to understanding the molecular mechanisms through which estrogens affect cognition. Biochimica et Biophysica Acta—Gen Subj 1800:1045–1055

    Article  CAS  Google Scholar 

  • Fuh JL, Wang SJ, Lee SJ, Lu SR, Juang KD (2006) A longitudinal study of cognition change during early menopausal transition in a rural community. Maturitas 53:447–453

    Article  PubMed  Google Scholar 

  • Gibbs RB, Aggarwal P (1998) Estrogen and basal forebrain cholinergic neurons: Implications for brain aging and Alzheimer's disease-related cognitive decline. Horm Behav 34: 98–111

    Article  PubMed  CAS  Google Scholar 

  • Gibbs RB (1998) Impairment of basal forebrain cholinergic neurons associated with aging and long-term loss of ovarian function. Exp Neurol 151:289–302

    Article  PubMed  CAS  Google Scholar 

  • Gibbs RB (2000) Long-term treatment with estrogen and progesterone enhances acquisition of a spatial memory task by ovariectomized aged rats. Neurobiol Aging 21:107–116

    Article  PubMed  CAS  Google Scholar 

  • Gilardi KV, Shideler SE, Valverde CR, Roberts JA, Lasley BL (1997) Characterization of the onset of menopause in the rhesus macaque. Biol Reprod 57:335–340

    Article  PubMed  CAS  Google Scholar 

  • Gold EB, Sternfeld B, Kelsey JL, Brown C, Mouton C, Reame N, Salamone L, Stellato R (2000) Relation of demographic and lifestyle factors to symptoms in a multi-racial/ethnic population of women 40–55 years of age. Am J Epidemiol 152:463–473

    Article  PubMed  CAS  Google Scholar 

  • Goldman-Rakic PS (1992) Working memory and the mind. Sci Am 2647:110–117

    Article  Google Scholar 

  • Goodman AL, Descalzi CD, Johnson DK, Hodgen GD (1977) Composite pattern of circulating LH, FSH, estradiol, and progesterone during the menstrual cycle in cynomolgus monkeys. Proc Soc Exp Biol Med 155:479–481

    PubMed  CAS  Google Scholar 

  • Gore AC, Windsor-Engnell BM, Terasawa E (2004) Menopausal increases in pulsatile gonadotropin-releasing hormone release in a nonhuman primate (Macaca mulatta). Endocrinology 145:4653–4659

    Article  PubMed  CAS  Google Scholar 

  • Grady D, Yaffe K, Kristof M, Lin F, Richards C, Barrett-Connor E (2002) Effect of postmenopausal hormone therapy on cognitive function: The Heart and Estrogen/progestin Replacement Study. Am J Med 113:543–548

    Article  PubMed  CAS  Google Scholar 

  • Gresack JE, Frick KM (2004) Environmental enrichment reduces the mnemonic and neural benefits of estrogen. Neuroscience 128:459–471

    Article  PubMed  CAS  Google Scholar 

  • Gresack JE, Kerr KM, Frick KM (2007) Life-long environmental enrichment differentially affects the mnemonic response to estrogen in young, middle-aged, and aged female mice. Neurobiol Learn Mem 88:393–408

    Article  PubMed  Google Scholar 

  • Grodstein F, Chen J, Pollen D, Albert M (2000) Postmenopausal hormone therapy and cognitive function in healthy older women. J Am Geriatr Soc 48:746–752

    PubMed  CAS  Google Scholar 

  • Halbreich U, Lumley LA, Palter S, Manning C, Gengo F, Joe SH (1995) Possible acceleration of age effects on cognition following menopause. J Psychiatr Res 29:153–163

    Article  PubMed  CAS  Google Scholar 

  • Hao J, Janssen WG, Tang Y, Roberts JA, McKay H, Lasley B, Allen PB, Greengard P, Rapp PR, Kordower JH, Hof PR, Morrison JH (2003) Estrogen increases the number of spinophilin-immunoreactive spines in the hippocampus of young and aged female rhesus monkeys. J Comp Neurol 465:540–550

    Article  PubMed  CAS  Google Scholar 

  • Hao J, Rapp PR, Leffler AE, Leffler SR, Janssen WG, Lou W, McKay H, Roberts JA, Wearne SL, Hof PR, Morrison JH (2006) Estrogen alters spine number and morphology in prefrontal cortex of aged female rhesus monkeys. J Neurosci 26:2571–2578

    Article  PubMed  CAS  Google Scholar 

  • Hao J, Rapp PR, Janssen WG, Lou W, Lasley BL, Hof PR, Morrison JH (2007) Interactive effects of age and estrogen on cognition and pyramidal neurons in monkey prefrontal cortex. Proc Natl Acad Sci, USA 104:11465–11470

    Article  PubMed  CAS  Google Scholar 

  • Harburger LL, Bennett JC, Frick KM (2007) Effects of estrogen and progesterone on spatial memory consolidation in aged females. Neurobiol Aging 28:602–610

    Article  PubMed  CAS  Google Scholar 

  • Herlitz A, Thilers P, Habib R (2007) Endogenous estrogen is not associated with cognitive performance before, during, or after menopause. Menopause 14:425–431

    Article  PubMed  Google Scholar 

  • Hogervorst E, Boshuisen M, Riedel WJ, Willekes C, Jolles J (1999) The effect of hormone replacement therapy on cognitive function in elderly women. Psychoneuroendocrinology 24:43–68

    Article  PubMed  CAS  Google Scholar 

  • Hojo Y, Hattori TA, Enami T, Furukawa A, Suzuki K, Ishii HT, Mukai H, Morrison JH, Janssen WG, Kominami S, Harada N, Kimoto T, Kawato S (2004) Adult male rat hippocampus synthesizes estradiol from pregnenolone by cytochromes P45017alpha and P450 aromatase localized in neurons. Proc Natl Acad Sci, USA 101:865–870

    Article  PubMed  CAS  Google Scholar 

  • Ishunina TA, Swaab DF (2007) Alterations in the human brain in menopause. Maturitas 57:20–22

    Article  PubMed  CAS  Google Scholar 

  • Ishunina TA, Fischer DF, Swaab DF (2007) Estrogen receptor alpha and its splice variants in the hippocampus in aging and Alzheimer’s disease. Neurobiol Aging 28:1670–1681

    Article  PubMed  CAS  Google Scholar 

  • Janowsky JS, Chavez B, Orwoll E (2000) Sex steroids modify working memory. J Cogn Neurosci 12:407–414

    Article  PubMed  CAS  Google Scholar 

  • Joffe H, Hall J, Gruber S, Sarmiento I (2006) Estrogen therapy selectively enhances prefrontal cognitive processes: A randomized, double-blind, placebo-controlled study with functional magnetic resonance imaging in perimenopausal and recently postmenopausal women. Menopause 13:411–422

    Article  PubMed  Google Scholar 

  • Kampen DL, Sherwin BB (1994) Estrogen use and verbal memory in healthy postmenopausal women. Obstet Gynecol 83:979–983

    Article  PubMed  CAS  Google Scholar 

  • Kandel ER, Schwartz JH, Jessell TM (2000) Principles of neural science, 4th ed. McGraw Hill, New York

    Google Scholar 

  • Keating NL, Cleary PD, Rossi AS, Zaslavsky AM, Ayanian JZ (1999) Use of hormone replacement therapy by postmenopausal women in the United States. Ann Intern Med 130:545–553

    PubMed  CAS  Google Scholar 

  • Knobil E, Neill J (1988) The menstrual cycle and its neuroendocrine control. The physiology of reproduction. Raven Press, New York, pp 1971–1994

    Google Scholar 

  • Koike S, Sakai M, Muramatsu M (1987) Molecular cloning and characterization of rat estrogen receptor cDNA. Nucleic Acids Res 15:2499–2513

    Article  PubMed  CAS  Google Scholar 

  • Kordower JH, Chen EY, Morrison JH (2010) Long-term gonadal hormone treatment and endogenous neurogenesis in the dentate gyrus of the adult female monkey. Exp Neurol 224:252–257

    Article  PubMed  CAS  Google Scholar 

  • Kretz O, Fester L, Wehrenberg U, Zhou L, Brauckmann S, Zhao S, Prange-Kiel J, Naumann T, Jarry H, Frotscher M, Rune GM (2004) Hippocampal synapses depend on hippocampal estrogen synthesis. J Neurosci 24:5913–5921

    Article  PubMed  CAS  Google Scholar 

  • Lacreuse A (2006) Effects of ovarian hormones on cognitive function in nonhuman primates. Neuroscience 138:859–867

    Article  PubMed  CAS  Google Scholar 

  • Lacreuse A, Herndon JG, Moss MB (2000) Cognitive function in aged ovariectomized female rhesus monkeys. Behav Neurosci 114:506–513

    Article  PubMed  CAS  Google Scholar 

  • Lacreuse A, Wilson ME, Herndon JG (2002) Estradiol, but not raloxifene, improves aspects of spatial working memory in aged ovariectomized rhesus monkeys. Neurobiol Aging 23:589–600

    Article  PubMed  CAS  Google Scholar 

  • Lacreuse A, Chhabra RK, Hall MJ, Herndon JG (2004) Executive function is less sensitive to estradiol than spatial memory: Performance on an analog of the card sorting test in ovariectomized aged rhesus monkeys. Behav Process 67:313–319

    Article  CAS  Google Scholar 

  • Laughlin GA, Kritz-Silverstein D, Barrett-Connor E (2010) Endogenous oestrogens predict 4 year decline in verbal fluency in postmenopausal women: The Rancho Bernardo Study. Clin Endocrinol 72:99–106

    Article  CAS  Google Scholar 

  • LeBlanc ES, Janowsky J, Chan BKS, Nelson HD (2001) Hormone replacement therapy and cognition. Systematic review and meta-analysis. J Am Med Assoc 285:1489–1499

    Article  CAS  Google Scholar 

  • LeBlanc E, Neiss M, Carello P, Samuels M (2007) Hot flashes and estrogen therapy do not influence cognition in early menopausal women. Menopause 14:191–202

    Article  PubMed  Google Scholar 

  • Lebrun CE, van der Schouw YT, de Jong FH, Pols HA, Grobbee DE, Lamberts SW (2005) Endogenous oestrogens are related to cognition in healthy elderly women. Clin Endocrinol 63:50–55

    Article  CAS  Google Scholar 

  • LeFevre J, McClintock MK (1988) Reproductive senescence in female rats: A longitudinal study of individual differences in estrous cycles and behavior. Biol Reprod 38:780–789

    Article  PubMed  CAS  Google Scholar 

  • Lewis MC, Kerr KM, Orr PT, Frick KM (2008a) Estradiol-induced enhancement of object memory consolidation involves NMDA receptors and protein kinase A in the dorsal hippocampus of female C57BL/6 mice. Behav Neurosci 122:716–721

    Article  PubMed  CAS  Google Scholar 

  • Lewis MC, Orr PT, Frick KM (2008b) Differential effects of acute progesterone administration on spatial and object memory in middle-aged and aged female C57BL/6 mice. Horm Behav 54:455–462

    Article  PubMed  CAS  Google Scholar 

  • Lord C, Buss C, Lupien S, Pruessner J (2008) Hippocampal volumes are larger in postmenopausal women using estrogen therapy compared to past users, never users and men: A possible window of opportunity effect. Neurobiol Aging 29:95–101

    Article  PubMed  CAS  Google Scholar 

  • Maki P (2005) A systematic review of clinical trials of hormone therapy on cognitive function: effects of age at initiation and progestin use. Ann N Y Acad Sci 1052:182–197

    Article  PubMed  CAS  Google Scholar 

  • Maki PM (2006) Hormone therapy and cognitive function: Is there a critical period for benefit? Neuroscience 138:1027–1030

    Article  PubMed  CAS  Google Scholar 

  • Maki PM, Zonderman AB, Resnick SM (2001) Enhanced verbal memory in nondemented elderly women receiving hormone-replacement therapy. Am J Psychiatry 158:227–233

    Article  PubMed  CAS  Google Scholar 

  • Markham JA, Pych JC, Juraska JM (2002) Ovarian hormone replacement to aged ovariectomized female rats benefits acquisition of the Morris water maze. Horm Behav 42:284–293

    Article  PubMed  CAS  Google Scholar 

  • Markowska AL (1999) Sex dimorphisms in the rate of age-related decline in spatial memory: Relevance to alterations in the estrous cycle. J Neurosci 19:8122–8133

    PubMed  CAS  Google Scholar 

  • Markowska AL, Savonenko AV (2002) Effectiveness of estrogen replacement in restoration of cognitive function after long-term estrogen withdrawal in aging rats. J Neurosci 22:10985–10995

    PubMed  CAS  Google Scholar 

  • Matthews KA, Kuller LH, Wing RR, Meilahn EN, Plantinga P (1996) Prior to use of estrogen replacement therapy, are users healthier than nonusers? Am J Epidemiol 143:971–978

    Article  PubMed  CAS  Google Scholar 

  • Matthews K, Cauley J, Yaffe K, Zmuda JM (1999) Estrogen replacement therapy and cognitive decline in older community women. J Am Geriatr Soc 47:518–523

    PubMed  CAS  Google Scholar 

  • McCarthy MM, Becker JB (2002) Neuroendocrinology of sexual behavior in the female. In: Becker JB, Breedlove SM, Crews D, McCarthy MM (eds) Behavioral endocrinology. MIT Press, Cambridge, MA, pp 117–151

    Google Scholar 

  • Milner TA, McEwen BS, Hayashi S, Li CJ, Reagan LP, Alves SE (2001) Ultrastructural evidence that hippocampal alpha estrogen receptors are located at extranuclear sites. J Comp Neurol 429:355–371

    Article  PubMed  CAS  Google Scholar 

  • Milner TA, Ayoola K, Drake CT, Herrick SP, Tabori NE, McEwen BS, Warrier S, Alves SE (2005) Ultrastructural localization of estrogen receptor beta immunoreactivity in the rat hippocampal formation. J Comp Neurol 491:81–95

    Article  PubMed  CAS  Google Scholar 

  • Miranda P, Williams CL, Einstein G (1999) Granule cells in aging rats are sexually dimorphic in their response to estradiol. J Neurosci 19:3316–3325

    PubMed  CAS  Google Scholar 

  • Nelson JF, Karelus K, Bergman MD, Felicio LS (1995) Neuroendocrine involvement in aging: Evidence from studies of reproductive aging and caloric restriction. Neurobiol Aging 16:837–843

    Article  PubMed  CAS  Google Scholar 

  • Osterlund MK, Keller E, Hurd YL (2000) The human forebrain has discrete estrogen receptor alpha messenger RNA expression: High levels in the amygdaloid complex. Neuroscience 95:333–342

    Article  PubMed  CAS  Google Scholar 

  • Phillips SM, Sherwin BB (1992) Effects of estrogen on memory function in surgically menopausal women. Psychoneuroendocrinology 17:485–495

    Article  PubMed  CAS  Google Scholar 

  • Rapp PR, Morrison JH, Roberts JA (2003a) Cyclic estrogen replacement improves cognitive function in aged ovariectomized rhesus monkeys. J Neurosci 23:5708–5714

    PubMed  CAS  Google Scholar 

  • Rapp SR, Espeland MA, Shumaker SA, Henderson VW, Brunner RL, Manson JE, Gass MLS, Stefanick ML, Lane DS, Hays J, Johnson KC, Coker LH, Dailey M, Bowen D (2003b) Effect of estrogen plus progestin on global cognitive function in postmenopausal women. The Women’s Health Initiative Memory Study: A randomized controlled trial. J Am Med Assoc 289:2663–2672

    Article  CAS  Google Scholar 

  • Resnick SM, Maki PM, Rapp SR, Espeland MA, Brunner R, Coker LH, Granek IA, Hogan P, Ockene JK, Shumaker SA (2006) Effects of combination estrogen plus progestin hormone treatment on cognition and affect. J Clin Endocrinol Metab 91:1802–1810

    Article  PubMed  CAS  Google Scholar 

  • Resnick S, Espeland M, An Y, Maki P, Coker L, Jackson R, Stefanick M, Wallace R, Rapp S (2009a) Effects of conjugated equine estrogens on cognition and affect in postmenopausal women with prior hysterectomy. J Clin Endocrinol Metab 94:4152–4161

    Article  PubMed  CAS  Google Scholar 

  • Resnick SM, Espeland MA, Jaramillo SA, Hirsch C, Stefanick ML, Murray AM, Ockene J, Davatzikos C (2009b) Postmenopausal hormone therapy and regional brain volumes: The WHIMS-MRI Study. Neurology 72:135–142

    Article  PubMed  CAS  Google Scholar 

  • Roberts JA, Gilardi KV, Lasley B, Rapp PR (1997) Reproductive senescence predicts cognitive decline in aged female monkeys. Neuroreport 8:2047–2051

    Article  PubMed  CAS  Google Scholar 

  • Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperbert C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women. J Am Med Assoc 288:321–333

    Article  CAS  Google Scholar 

  • Savonenko AV, Markowska AL (2003) The cognitive effects of ovariectomy and estrogen replacement are modulated by aging. Neuroscience 119:821–830

    Article  PubMed  CAS  Google Scholar 

  • Sherwin BB (1988) Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women. Psychoneuroendocrinology 13:345–357

    Article  PubMed  CAS  Google Scholar 

  • Sherwin BB, Henry JF (2008) Brain aging modulates the neuroprotective effects of estrogen on selective aspects of cognition in women: A critical review. Front Neuroendocrinol 29:88–113

    Article  PubMed  CAS  Google Scholar 

  • Shughrue PJ, Merchenthaler I (2000) Evidence for novel estrogen binding sites in the rat hippocampus. Neuroscience 99:605–612

    Article  PubMed  CAS  Google Scholar 

  • Shughrue P, Scrimo P, Lane M, Askew R, Merchenthaler I (1997) The distribution of estrogen receptor-ß mRNA in forebrain regions of the estrogen receptor-α knockout mouse. Endocrinology 138:5649–5652

    Article  PubMed  CAS  Google Scholar 

  • Shughrue PJ, Scrimo PJ, Merchenthaler I (2000) Estrogen binding and estrogen receptor characterization (ERα and ERß) in the cholinergic neurons of the rat basal forebrain. Neuroscience 96:41–49

    Article  PubMed  CAS  Google Scholar 

  • Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, Fillit H, Stefanick ML, Hendrix SL, Lewis CE, Masaki K, Coker LH (2004) Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women’s Health Initiative Memory Study. J Am Med Assoc 291:2947–2958

    Article  CAS  Google Scholar 

  • Soules MR, Sherman S, Parrott E, Rebar R, Santoro N, Utian W, Woods N (2001) Stages of reproductive aging workshop (STRAW). J Womens Health Gend Based Med 10:843–848

    Article  PubMed  CAS  Google Scholar 

  • Spencer JL, Waters EM, Romeo RD, Wood GE, Milner TA, McEwen BS (2008) Uncovering the mechanisms of estrogen effects on hippocampal function. Front Neuroendocrinol 29:219–237

    Article  PubMed  CAS  Google Scholar 

  • Spreafico E, Bettini E, Pollio G, Maggi A (1992) Nucleotide sequence of estrogen receptor cDNA from Sprague-Dawley rat. Eur J Pharmacol 227:353–356

    Article  PubMed  CAS  Google Scholar 

  • Squire LR (1992) Memory and the hippocampus: A synthesis from findings with rats, monkeys, and humans. Psychol Rev 99:195–231

    Article  PubMed  CAS  Google Scholar 

  • Steffens D, Norton M, Plassman B, Tschanz J (1999) Enhanced cognitive performance with estrogen use in nondemented community-dwelling older women. J Am Geriatr Soc 47:1171–1175

    PubMed  CAS  Google Scholar 

  • Talboom JS, Williams BJ, Baxley ER, West SG, Bimonte-Nelson HA (2008) Higher levels of estradiol replacement correlate with better spatial memory in surgically menopausal young and middle-aged rats. Neurobiol Learn Mem 90:155–163

    Article  PubMed  CAS  Google Scholar 

  • Tanapat P, Hastings NB, Reeves, AJ, Gould E (1999) Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat. J Neurosci 19:5792–5801

    PubMed  CAS  Google Scholar 

  • Tang Y, Janssen WG, Hao J, Roberts JA, McKay H, Lasley B, Allen PB, Greengard P, Rapp PR, Kordower JH, Hof PR, Morrison JH (2004) Estrogen replacement increases spinophilin-immunoreactive spine number in the prefrontal cortex of female rhesus monkeys. Cereb Cortex 14:215–223

    Article  PubMed  Google Scholar 

  • Thilers PP, Macdonald SW, Nilsson LG, Herlitz A (2010) Accelerated postmenopausal cognitive decline is restricted to women with normal BMI: Longitudinal evidence from the Betula project. Psychoneuroendocrinology 35:516–524

    Article  PubMed  Google Scholar 

  • Tigges J, Gordon TP, McClure HM, Hall EC, Peters A (1988) Survival rate and life span of rhesus monkeys at the Yerkes Regional Primate Research Center. Am J Primatol 15:263–273

    Article  Google Scholar 

  • Tremblay GB, Tremblay A, Copeland NG, Gilbert DJ, Jenkins NA, Labrie F, Giguere V (1997) Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor beta. Mol Endocrinol 11:353–365

    Article  PubMed  CAS  Google Scholar 

  • United States Census Bureau (2008) National Population Projections. http://www.census.gov/population/www/projections/2008projections.html

  • United States National Center for Health Statistics (2009) Deaths: Final Data for 2006. National Vital Statistics Reports (NVSR) 57 (14)

    Google Scholar 

  • Viscoli C, Brass L, Kernan W, Sarrel P (2005) Estrogen therapy and risk of cognitive decline: Results from the women’s estrogen for stroke trial (WEST). Am J Obstet Gynecol 192:387–393

    Article  PubMed  CAS  Google Scholar 

  • Voytko ML (2000) The effects of long-term ovariectomy and estrogen replacement therapy on learning and memory in monkeys (Macaca fascicularis). Behav Neurosci 114:1078–1087

    Article  PubMed  CAS  Google Scholar 

  • Voytko ML (2002) Estrogen and the cholinergic system modulate visuospatial attention in monkeys (Macaca fascicularis). Behav Neurosci 116:187–197

    Article  PubMed  CAS  Google Scholar 

  • Voytko ML, Higgs CJ, Murray R (2008) Differential effects on visual and spatial recognition memory of a novel hormone therapy regimen of estrogen alone or combined with progesterone in older surgically menopausal monkeys. Neuroscience 154:1205–1217

    Article  PubMed  CAS  Google Scholar 

  • Voytko ML, Tinkler GP, Browne C, Tobin JR (2009) Neuroprotective effects of estrogen therapy for cognitive and neurobiological profiles of monkey models of menopause. Am J Primatol 71:794–801

    Article  PubMed  Google Scholar 

  • Walf AA, Rhodes ME, Frye CA (2006) Ovarian steroids enhance object recognition in naturally cycling and ovariectomized, hormone-primed rats. Neurobiol Learn Mem 86:35–46

    Article  PubMed  CAS  Google Scholar 

  • Wang JM, Liu L, Brinton RD (2008) Estradiol-17beta-induced human neural progenitor cell proliferation is mediated by an estrogen receptor beta-phosphorylated extracellularly regulated kinase pathway. Endocrinology 149:208–218

    Article  PubMed  CAS  Google Scholar 

  • Warren SG, Humphreys AG, Juraska JM, Greenough WT (1995) LTP varies across the estrous cycle: Enhanced synaptic plasticity in proestrus rats. Brain Res 703:26–23

    Article  PubMed  CAS  Google Scholar 

  • Wise PM (2000) New understanding of the complexity of the menopause and challenges for the future. In: Bellino FL (ed) Proceedings of the international symposium on the biology of menopause. Springer, Norwell, MA, pp 1–8

    Chapter  Google Scholar 

  • Wise PM, Dubal DB, Wilson ME, Rau SW, Liu Y (2001) Estrogens: Trophic and protective factors in the adult brain. Front Neuroendocrinol 22:33–66

    Article  PubMed  CAS  Google Scholar 

  • Wolf OT, Kirschbaum C (2002) Endogenous estradiol and testosterone levels are associated with cognitive performance in older women and men. Horm Behav 41:259–266

    Article  PubMed  CAS  Google Scholar 

  • Wolf OT, Kudielka BM, Hellhammer DH, Törber S, McEwen BS, Kirschbaum C (1999) Two weeks of transdermal estradiol treatment in postmenopausal elderly women and its effect on memory and mood: Verbal memory changes are associated with the treatment induced estradiol levels. Psychoneuroendocrinology 24:727–741

    Article  PubMed  CAS  Google Scholar 

  • Woodruff-Pak DS (1997) Neuropsychology of Aging. Blackwell Publishers, Malden, MA

    Google Scholar 

  • Woolley CS, McEwen BS (1992) Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat. J Neurosci 12:2549–2554

    PubMed  CAS  Google Scholar 

  • Woolley CS, McEwen BS (1993) Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat. J Comp Neurol 336:293–306

    Article  PubMed  Google Scholar 

  • Wu X, Glinn MA, Ostrowski NL, Su Y, Ni B, Cole HW, Bryant HU, Paul SM (1999) Raloxifene and estradiol benzoate both fully restore hippocampal choline acetyltransferase activity in ovariectomized rats. Brain Res 847:98–104

    Article  PubMed  CAS  Google Scholar 

  • Yaffe K, Sawaya G, Lieberburg I, Grady D (1998) Estrogen therapy in postmenopausal women: Effects on cognitive function and dementia. J Am Med Assoc 279:688–695

    Article  CAS  Google Scholar 

  • Yaffe K, Lui LY, Grady D, Cauley J, Kramer J, Cummings SR (2000) Cognitive decline in women in relation to non-protein-bound oestradiol concentrations. Lancet 356:708–712

    Article  PubMed  CAS  Google Scholar 

  • Yaffe K, Barnes D, Lindquist K, Cauley J, Simonsick EM, Penninx B, Satterfield S, Harris T, Cummings SR (2007) Endogenous sex hormone levels and risk of cognitive decline in an older biracial cohort. Neurobiol Aging 28:171–178

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi-Shima N, Yuri K (2007) Age-related changes in the expression of ER-β mRNA in the female rat brain. Brain Res 1155:34–41

    Article  PubMed  CAS  Google Scholar 

  • Zandi PP, Carlson MC, Plassman BL, Welsh-Bohmer KA, Mayer LS, Steffens DC, Breitner JCS (2002) Hormone replacement therapy and incidence of Alzheimer disease in older women. J Am Med Assoc 288:2123–2129

    Article  CAS  Google Scholar 

  • Zhao L, O’Neill K, Brinton RD (2005) Selective estrogen receptor modulators (SERMs) for the brain: Current status and remaining challenges for developing NeuroSERMs. Brain Res Rev 49:472–493

    Article  PubMed  CAS  Google Scholar 

  • Zhao Z, Fan L, Frick KM (2010) Epigenetic alterations regulate the estradiol-induced enhancement of memory consolidation. Proc Natl Acad Sci, USA 107:5605–5610

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was sponsored by the University of Wisconsin-Milwaukee and Yale University.

Author information

Authors and Affiliations

  1. Department of Psychology, University of Wisconsin-Milwaukee, 2441 E. Hartford Ave, Milwaukee, WI 53211, USA

    Marissa I. Boulware & Karyn M. Frick

  2. Department of Psychology, Yale University, New Haven, CT 06520, USA

    Brianne A. Kent

Authors
  1. Marissa I. Boulware
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brianne A. Kent
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karyn M. Frick
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Karyn M. Frick .

Editor information

Editors and Affiliations

  1. School of Biomedical Sciences, Inst. Neuroscience, University of Nottingham, Nottingham, NG7 2UH, United Kingdom

    Marie-Christine Pardon

  2. Div. Geriatric Psychiatry, University of California, San Diego, Gilman Drive 9500, La Jolla, 92093-0603, California, USA

    Mark W. Bondi

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Boulware, M.I., Kent, B.A., Frick, K.M. (2011). The Impact of Age-Related Ovarian Hormone Loss on Cognitive and Neural Function. In: Pardon, MC., Bondi, M. (eds) Behavioral Neurobiology of Aging. Current Topics in Behavioral Neurosciences, vol 10. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2011_122

Download citation

Publish with us

Policies and ethics

Search

Navigation