Advertisement

Journal of Molecular Neuroscience

, Volume 20, Issue 3, pp 385–393 | Cite as

Steroid hormones and cognitive functioning in aging men

A mini-review
  • Barbara B. SherwinEmail author
Alzheimer’s Therapeutics: Cognitive Enhancement

Abstract

The decrease in testosterone (T) production in aging men has been well documented. Because the majority of circulating estradiol (E2) in men arises through aromatization of T, levels of E2 decrease as well with increasing age. It is also clear that some proportion of men develop impairments in aspects of cognition, particularly in explicit memory and language abilities with normal aging. Although there is a paucity of studies that have attempted to determine whether the decline in the endocrine and cognitive changes in older men are related, findings from the extant literature provide some support for the notion that estrogen is important for aspects of memory in aging men, just as it is in women, whereas T helps to maintain visuospatial abilities. More definitive conclusions on the relationship between the sex hormones and specific cognitive functions in men awaitmore careful investigation in this area in the future.

Index Entries

Estrogen testosterone cortisol cognition aging men 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Albert S. A., Michalls K., and Padilla M. (1999) Functional significance of mild cognitive impairment in elderly patients withoug a dementia diagnosis. Am. J. Geriatr. Psychiatry 7, 213–220.PubMedGoogle Scholar
  2. Alexander G. M., Swerdloff R. S., Wang C., Davidson T., McDonald V., Steiner B., and Hines M. (1998) Androgen-behavior correlations in hypogonadal men and eugonadal men. II. Cognitive abilities. Horm. Behav. 33, 85–94.PubMedCrossRefGoogle Scholar
  3. Ashman T. A., Mohss R. C., and Harvey P. D. (1999) Cognition and aging, Principles of Geriatric Medicine and Gerontology, 4th ed., in Hazzard W.R. et al., eds., McGraw-Hill, New York, pp. 1219–1228.Google Scholar
  4. Bardin C. W., Swerdloff R. S., and Santen R. J. (1991) Androgens: risks and benefits. J. Clin. Endocrinol. Metab. 73, 4–7.PubMedGoogle Scholar
  5. Barrett-Connor E., Goodman-Gruen D., and Patay B. (1999) Endogenous sex hormones and cognitive function in older men. J. Clin. Endocrinol. Metab. 84, 3681–3685.PubMedCrossRefGoogle Scholar
  6. Bourdeau I., Baid C., Noel B., Leclerc I., Cordeau M. P., Belair M., et al. (2002) Loss of brain volume in endogenous Cushing’s syndrome and its reversibility after correction of hypercortisolims. J. Clin. Endocrinol. Metab. 87, 1949–1954.PubMedCrossRefGoogle Scholar
  7. Carlson L. E. and Sherwin B. B. (2000) Higher levels of plasma estradiol and testosterone in healthy elderly men compared with age-matched women may protect aspects of explicit memory. Menopause 7, 168–177.PubMedCrossRefGoogle Scholar
  8. Carlson L. E., Sherwin B. B., and Chertkow H. M. (1999) Relationships between dehydroepiandrosterone sulfate (DHEAS) and cortisol (CRT) plasma levels and everyday memory in Alzheimer’s disease patients compared to healthy controls. Horm. Behav. 35, 254–263.PubMedCrossRefGoogle Scholar
  9. Cherrier M. M., Anawalt B. D., Herbst K. L., Amory J. K., Craft S., Matsumoto A. M., and Bremner W. J. (2002) Cognitive effects of short-term manipulation of serum sex steroids in healthy young men. J. Clin. Endocrinol. Metab. 87, 3090–3096.PubMedCrossRefGoogle Scholar
  10. Cherrier M. M., Asthana S., Plymate S., Baker L., Matsumoto A. M., Peskind E., et al. (2001) Testosterone supplementation improves spatial and verbal memory in healthy older men. Neurology 57, 80–88.PubMedCrossRefGoogle Scholar
  11. Chertkow H. (1998) Mild memory loss in the elderly: can we predict development in dementia? Can. J. Neurolog. Sci. 25, 1–64.Google Scholar
  12. Christiansen K. (1993) Sex hormone-related variations of cognitive performance in Kung San hunter-gatherers of Namibia. Neuropsychobiology 27, 97–107.PubMedCrossRefGoogle Scholar
  13. Collaer M. L. and Hines M. (1995) Human behavioral sex differences: a role for gonadal hormones during early development? Psychol. Bull. 118, 55–107.PubMedCrossRefGoogle Scholar
  14. Craik F. I. M. (1991) Memory functions in normal aging, in: Memory Disorders (Yanagihara T. and Petersen R. C., eds.), New York: Marcel Dekker Inc., pp. 347–367.Google Scholar
  15. Crook T. H., Bartus R. T., Ferris S. H., Whitehouse P., Cohen G. D., and Gershon S. (1996) Age-associated memory impairment: proposed diagnostic criteria and measures of clinical change—rReport of a National Institute of Mental Health workgroup. Dev. Neuropsychol. 2, 261–276.Google Scholar
  16. de la Torre J. C., Fortin T., Park G. A., Butler K. S., Kozlowski P., Pappas B. A., et al. (1992) Chronic cerebrovascular insufficiency induces dementia-like deficits in aged rats. Brain Res. 582, 186–195.PubMedCrossRefGoogle Scholar
  17. Denti L., Pasolini G., Sanfelici L., Benedetti R., Cecchetti A., Ceda G. P., et al. (2000) Aging-related decline of gonadal function in healthy men: correlation with body composition and lipoproteins. J. Am. Geriatr. Soc. 48, 51–58.PubMedGoogle Scholar
  18. Diagnostic and Statistical Manual of Mental Disorders: Fourth Edition. (1994) American Psychiatric Association, Washington, DC.Google Scholar
  19. Feldman H. A., Longcope C., Derby C. A., Johannes C. B., Araujo A. B., Coviello A. D., Bremner W. J., and McKinlay J. B. (2002) Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J. Clin. Endocrinol. Metab. 87, 589–598.PubMedCrossRefGoogle Scholar
  20. Ferrini R. L. and Barrett-Connor E. (1998) Sex hormones and age: a cross-sectional study of testosterone and estradiol and their bioavailable fractions in community-dwelling men. Am. J. Epidemiol. 147, 750–754.PubMedGoogle Scholar
  21. Forster M. J., Dubey A., Dawson K. M., Stutts W. A., Lal H., and Sohal R. S. (1996) Age-related losses of cognitve function and motor skills in mice are associated with oxidative protein damage in the brain. Proc. Natl. Acad. Sci. U.S.A. 93, 4765–4769.CrossRefGoogle Scholar
  22. Ganguli M., Belle S., Ratcliff G., Seaberg E., Huff F. J., von der Porten K., and Kuller L. H. (1993) Sensitivity and specificity for dementia of population-based criteria for cognitive impairment: the MoVIES project. J Gerontol. 48, M152-M161.PubMedGoogle Scholar
  23. Gilmore R. (1995) Evoked potentials in the elderly. J. Clin. Neurophysiol. 12, 132–138.PubMedCrossRefGoogle Scholar
  24. Gorski R. A. (1991) Sexual differentiation of the endocrine brain and its control, in Brain Endocrinology (Motta M., ed.), Raven Press, New York, pp. 71–104.Google Scholar
  25. Gouchie C. and Kimura D. (1991) The relation between T levels and cognitive ability patterns. Psychoneuroendocrinology 16, 323–324.PubMedCrossRefGoogle Scholar
  26. Halpern D. F. (1992) Sex Differences in Cognitive Abilities, 2nd ed., L. Erlbaum Associates, Hillsdale, NJ.Google Scholar
  27. Hanninen T., Koivisto K., Reinikainen K. J., Helkala E. L., Soininen H., Mykkanen L., et al. (1996) Prevalence of ageing-associated cognitive decline in an elderly population. Age Ageing 25, 201–205.CrossRefGoogle Scholar
  28. Harman S. M., Metter E. J., Tobin J. D., Pearson J., and Blackman M. R. (2001) Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J. Clin. Endocrinol. Metab. 86, 724–731.PubMedCrossRefGoogle Scholar
  29. Huppert F. A. and Van Kierkerk J. K. (2001) Dehydroepiandrosterone (DHEA) supplementation for cognitive function. Cochrane Database Syst. Rev. CD000304.Google Scholar
  30. Jacobs D. M., Tang M. X., Stern Y., Sano M., Marder K., Bell K. L., et al. (1998) Cognitive function in nondemented older women who took estrogen after menopause. Neurology 50, 368–373.PubMedGoogle Scholar
  31. Janowsky J. S., Chavez B., and Orwoll E. (2000) Sex steroids modify working memory. J. Cogn. Neurosci. 12, 407–414.PubMedCrossRefGoogle Scholar
  32. Jorm A. F., Korten A. E., and Henderson A. S. (1987) The prevalence of dementia: a quantitative integration of the literature. Acta Psychiatr. Scand. 76, 465–479.PubMedGoogle Scholar
  33. Kampen D. L. and Sherwin B. B. (1994) Estrogen use and verbal memory in healthy postmenopausal women. Obstet. Gynecol. 83, 979–983.PubMedCrossRefGoogle Scholar
  34. Kampen D. L. and Sherwin B. B. (1996) Estradiol is related to visual memory in healthy young men. Behav. Neurosci. 110, 613–617.CrossRefGoogle Scholar
  35. Keefover RW. (1998) Aging and cognition. Neurol. Clin. North Am. 16, 635–648.Google Scholar
  36. Khosla S., Melton L. J. III, and Riggs B. L. (2002) Clinical review 144: Estrogen and the male skeleton. J. Clin. Endocrinol. Metab. 87, 1443–1450.PubMedCrossRefGoogle Scholar
  37. Kimonides V. G., Khatibi N. H., Svendsen C. N., Sofroniew M. V., and Herbert J. (1998) Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) protect hippocampal neurons against excitatory amino acid-induced neurotoxicity. Proc. Natl. Acad. Sci. U.S.A. 95, 1852–1857.PubMedCrossRefGoogle Scholar
  38. Labrie F., Belanger A., Simard J., Van L., and Labrie C. (1995) DHEA and peripheral androgen and estrogen formation: intracinology. Ann. N. Y. Acad. Sci. 774, 16–28.PubMedCrossRefGoogle Scholar
  39. Larrabee G. J. and Crook T. H. III (1994) Estimated prevalence of age-associated memory impairment derived from standardized tests of memory function. Int. Psychogeriatr. 6, 95–104.PubMedCrossRefGoogle Scholar
  40. Lee S. J. and McEwen B. S. (2001) Neurotrophic and neuroprotective actions of estrogens and their therapeutic implications. Annu. Rev. Pharmacol. Toxicol. 41, 569–591.PubMedCrossRefGoogle Scholar
  41. Levy R. (1994) Aging associated cognitive decline. Working Party in the International Psychogeriatric Association in collaboration with the World Health Organization [published erratum appears in Int. Psychogeriatr. 1994 6(2), 133]. Int. Psychogeriatr. 6(1), 63–68.PubMedCrossRefGoogle Scholar
  42. Lupien S. J., Wilkinson C. W., Brière S., Ng Ying Kin N. M. K., Meaney N. J., and Nair N. P. V. (2002) Acute modulation of aged human memory by pharmacological manipulation of glucocorticoids. J. Clin. Endocrinol. Metab. 87, 3798–3807.PubMedCrossRefGoogle Scholar
  43. Lupien S., Lecours A. R., Lussier I., Schwartz G., Nair N. P., and Meaney M. J. (1994) Basal cortisol levels and cognitive deficits in human aging. J. Neurosci. 14, 2893–2903.PubMedGoogle Scholar
  44. Lupien S. J., de Leon M., de Santi S., Convit A., Tarshish C., Nair N. P., et al. (1998) Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nat. Neurosci. 1, 69–73.PubMedCrossRefGoogle Scholar
  45. Marquis S., Moore M. M., Howieson D. B., Sexton G., Payami H., Kaye J. A., and Camicioli R. (2002) Independent predictors of cognitive decline in healthy elderly persons. Arch. Neurol. 59, 601–606.PubMedCrossRefGoogle Scholar
  46. McGeer E. and McGeer P.L. (1976) Age changes in humans for some enzimes associated with the metabolism of catecholamines, GABA, and acetylcholine, in Neurobiology of Aging (Terry R. D. and Gershon S., eds.), Raven Press, New York.Google Scholar
  47. Miles C., Green R., Sanders G., and Hines M. (1998) Estrogen and memory in a transsexual population. Horm. Behav. 34, 199–208.PubMedCrossRefGoogle Scholar
  48. Morales A., Heaton J. P., and Carson C. C. III (2000) Andropause: a misnomer for a true clinical entity. J. Urol. 163, 705–712.PubMedCrossRefGoogle Scholar
  49. Naftolin F. and Ryan K. J. (1975) The metabolism of androgens in central neuroendocrine tissues. J. Steroid Biochem. 6, 993–997.PubMedCrossRefGoogle Scholar
  50. Naveh-Benjamin M. (2001) Adult-age differences in memory performance: tests of an associative deficit hypothesis. J. Exp. Psychol. Learn. Mem. Cogn. 26, 1170–1187.Google Scholar
  51. O’Connor D. B., Archer J., Hair W. M., and Wu F. C. (2001) Activational effects of testosterone on cognitive function in men. Neuropsychologia 39, 1385–1394.PubMedCrossRefGoogle Scholar
  52. Peacock J. M., Folsom A. R., Knopman D. S., Mosley T. H., Goff D. C., Jr., and Szklo M. (1999) Association of nonsteroidal anti-inflammatory drugs and aspirin with cognitive performance in middle-aged adults. Neuroepidemiology 18, 134–143.PubMedCrossRefGoogle Scholar
  53. Perry P. J., Lund B. C., Arndt S., Holman T., Bever-Stille K. A., Paulsen J., and Demers L. M. (2001) Bioavailable testosterone as a correlate of cognition, psychological status, quality of life, and sexual function in aging males: implications for testosterone replacement therapy. Ann. Clin. Psychiatry 13, 75–80.PubMedCrossRefGoogle Scholar
  54. Peters A., Sethares C., and Moss M. B. (1998) The effects of aging on layer 1 in area 46 of prefrontal cortex in the rhesus monkey. Cereb. Cortex 8, 671–684.PubMedCrossRefGoogle Scholar
  55. Petersen R. C., Smith G. E., Waring S. C., Ivnik R. J., Tangalos E. G., and Kokmen E. (1999) Mild cognitive impairment: clinical characterization and outcome. Arch. Neurol. 56, 303–308.PubMedCrossRefGoogle Scholar
  56. Phoenix C. H., Goy R. W., Gerall A. A., and Young W. C. (1959) Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig. Endocrinology 65, 369–382.PubMedGoogle Scholar
  57. Plymate S. R., Tenover J. S., and Bremner W. J. (1989) Circadian variation in testosterone, sex hormone-binding globulin, and calculated non-sex hormone-binding globulin bound testosterone in healthy young and elderly men. J. Androl. 10, 366–371.PubMedGoogle Scholar
  58. Rabbitt P. and Lowe C. (2000) Patterns of cognitive ageing. Psychol. Res. 63, 308–316.PubMedCrossRefGoogle Scholar
  59. Rapp P. R. and Amaral D. G. (1992) Individual differences in the cognitive and neurobiological consequences of normal aging. Trends Neurosci. 15, 340–345.PubMedCrossRefGoogle Scholar
  60. Rasmuson S., Masman B., Carlstrom K., and Olsson T. (2001) Increased levels of adrenocortical and gonadal hormones in mild to moderate Alzheimer’s disease. Dementia Geriatr. Cogn. Disord. 13, 74–79.CrossRefGoogle Scholar
  61. Ruff R. M. and Parker S. B. (1993) Gender- and age-specific changes in motor speed and eye-hand coordination in adults: normative values for the Finger Tapping and Grooved Pegboard Tests. Percept. Mot. Skills 76, 1219–1230.PubMedGoogle Scholar
  62. Salthouse T. A. (1990) Working memory as a processing resource in cognitive aging. Dev. Rev. 10, 101–124.CrossRefGoogle Scholar
  63. Salthouse T. A. (1992) Mechanisms of Age-Cognition Relations in Adulthood. Erlbaum, Hilsdale, N.J.Google Scholar
  64. Seidman S. N., Spatz E., Rizzo C., and Roose S. P. (2001) Testosterone replacement therapy for hypogonadal men with major depressive disorder: a randomized, placebo-controlled clinical trial. J. Clin. Psychiatry 62, 406–412.PubMedCrossRefGoogle Scholar
  65. Sherwin B. B. (1997) Estrogen effects on cognition in menopausal women. Neurology 48, S21-S26.PubMedGoogle Scholar
  66. Sherwin B. B. and Phillips S. M. (1990) Estrogen and cognitive functioning in surgically menopausal women. Ann. N. Y. Acad. Sci. 592, 474–475.CrossRefGoogle Scholar
  67. Sherwin B. B. (1994) Estrogenic effects on memory in women. Ann. N. Y. Acad. Sci. 743, 213–230.PubMedCrossRefGoogle Scholar
  68. Sherwin B. B. and Tulandi T. (1996) “Add-back” estrogen reverses cognitive deficits induced by a gonadotropin-releasing hormone agonist in women with leiomyomata uteri. J. Clin. Endocrinol. Metab. 81, 2545–2549.CrossRefGoogle Scholar
  69. Sherwin B. B. (2003) Estrogen and cognitive functioning in women. Endocrine Rev. 24, 133–151.CrossRefGoogle Scholar
  70. Silverman I., Kastuk D., Choi J., and Phillips K. (1999). Testosterone levels and spatial ability in men. Psychoneuroendocrinology 24, 813–822.PubMedCrossRefGoogle Scholar
  71. Simerly R., Chang C., Muramatsu M., and Swanson L. (1990) Distribution of androgen and estrogen receptor nRNA-containing cells in the rat brain: an in situ hybridization study. J. Comp. Neurol. 294, 76–95.PubMedCrossRefGoogle Scholar
  72. Slabbekoorn D., van Goozen S. H., Megens J., Gooren L. J., and Cohen-Kettenis P. T. (1999) Activating effects of cross-sex hormones on cognitive functioning: a study of short-term and long-term hormone effects in trans-sexuals. Psychoneuroendocrinology 24, 423–447.PubMedCrossRefGoogle Scholar
  73. Small S. A., Stern Y., Tang M., and Mayeux R. (1999a) Selective decline in memory function among healthy elderly. Neurology 52, 1392–1396.PubMedGoogle Scholar
  74. Small S. A., Perera G. M., DeLaPaz R., Mayeux R., and Stern Y. (1999b) Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer’s disease. Ann. Neurol. 45, 466–472.PubMedCrossRefGoogle Scholar
  75. Small S. A. (2001) Age-related memory decline: current concepts and future directions. Arch. Neurol. 58, 360–364.PubMedCrossRefGoogle Scholar
  76. Starkman M. N., Gebarski S. S., Berent S., and Schteingart D. E. (1992) Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing’s syndrome. Biol. Psychiatry 32, 756–765.PubMedCrossRefGoogle Scholar
  77. Sternbach H. (1998) Age-associated testosterone decline in men: clinical issues for psychiatry. Am. J. Psychiatry 155, 1310–1318.PubMedGoogle Scholar
  78. Svec F. and Lopez A. (1989) Antiglucocorticoid actions of dehydroepiandrosterone and low concentrations in Alzheimer’s disease. Lancet 2, 1335–1336.PubMedCrossRefGoogle Scholar
  79. Taylor E. M. (1959) Psychological Appraisal of Children with Cerebral Defects. Harvard University Press, Cambridge, MA.Google Scholar
  80. Tenover J. S. (1992) Effects of testosterone supplementation in the aging male. J. Clin. Endocrinol. Metab. 75, 1092–1098.PubMedCrossRefGoogle Scholar
  81. Tenover J. S., Dahl K. D., Hsueh A. J., Lim P., Matsumoto A. M., and Bremner W. J. (1987) Serum bioactive and immunoreactive follicle-stimulating hormone levels and the response to clomiphene in healthy young and elderly men. J. Clin. Endocrinol. Metab. 64, 1103–1108.PubMedCrossRefGoogle Scholar
  82. Wolf O. T. and Kirschbaum C. (2002) Endogenous estradiol and testosterone levels are associated with cognitive performance in older women and men. Horm. Behav. 41, 259–266.PubMedCrossRefGoogle Scholar
  83. Wolkowitz O. M., Reus, V. I., Weingartner H., Thompson K., Breier A., Doran A., et al. (1990) Cognitive effects of corticosteroids. Am. J. Psychiatry 147, 1297–1303.PubMedGoogle Scholar
  84. Yaffe K., Lui L. Y., Zmuda J., and Cauley J. (2002) Sex hormones and cognitive function in older men. J. Am. Geriatr. Soc. 50, 707–712.PubMedCrossRefGoogle Scholar
  85. Yen S. S., Morales A. J., and Khorram O. (1995) Replacement of DHEA in aging men and women. Potential remedial effects. Ann. N. Y. Acad. Sci. 774, 128–142.PubMedCrossRefGoogle Scholar
  86. Zelinski E. M. and Burnight K. P. (1997) Sixteen-year longitudinal and time lag changes in memory and cognition in older adults. Psychol. Aging 12, 503–513.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2003

Authors and Affiliations

  1. 1.Department of Psychology and Department of OB/GYNMcGill UniversityMontrealCanada

Personalised recommendations