Skip to main content
SpringerLink
Log in

Steroid hormones and cognitive functioning in aging men

A mini-review

  • Alzheimer’s Therapeutics: Cognitive Enhancement
  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

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.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Bardin C. W., Swerdloff R. S., and Santen R. J. (1991) Androgens: risks and benefits. J. Clin. Endocrinol. Metab. 73, 4–7.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Chertkow H. (1998) Mild memory loss in the elderly: can we predict development in dementia? Can. J. Neurolog. Sci. 25, 1–64.

    Google Scholar 

  • Christiansen K. (1993) Sex hormone-related variations of cognitive performance in Kung San hunter-gatherers of Namibia. Neuropsychobiology 27, 97–107.

    Article  PubMed  CAS  Google Scholar 

  • Collaer M. L. and Hines M. (1995) Human behavioral sex differences: a role for gonadal hormones during early development? Psychol. Bull. 118, 55–107.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Diagnostic and Statistical Manual of Mental Disorders: Fourth Edition. (1994) American Psychiatric Association, Washington, DC.

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Gilmore R. (1995) Evoked potentials in the elderly. J. Clin. Neurophysiol. 12, 132–138.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Gouchie C. and Kimura D. (1991) The relation between T levels and cognitive ability patterns. Psychoneuroendocrinology 16, 323–324.

    Article  PubMed  CAS  Google Scholar 

  • Halpern D. F. (1992) Sex Differences in Cognitive Abilities, 2nd ed., L. Erlbaum Associates, Hillsdale, NJ.

    Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Huppert F. A. and Van Kierkerk J. K. (2001) Dehydroepiandrosterone (DHEA) supplementation for cognitive function. Cochrane Database Syst. Rev. CD000304.

  • 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.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Kampen D. L. and Sherwin B. B. (1994) Estrogen use and verbal memory in healthy postmenopausal women. Obstet. Gynecol. 83, 979–983.

    Article  PubMed  CAS  Google Scholar 

  • Kampen D. L. and Sherwin B. B. (1996) Estradiol is related to visual memory in healthy young men. Behav. Neurosci. 110, 613–617.

    Article  Google Scholar 

  • Keefover RW. (1998) Aging and cognition. Neurol. Clin. North Am. 16, 635–648.

    CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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 

  • Miles C., Green R., Sanders G., and Hines M. (1998) Estrogen and memory in a transsexual population. Horm. Behav. 34, 199–208.

    Article  PubMed  CAS  Google Scholar 

  • Morales A., Heaton J. P., and Carson C. C. III (2000) Andropause: a misnomer for a true clinical entity. J. Urol. 163, 705–712.

    Article  PubMed  CAS  Google Scholar 

  • Naftolin F. and Ryan K. J. (1975) The metabolism of androgens in central neuroendocrine tissues. J. Steroid Biochem. 6, 993–997.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Rabbitt P. and Lowe C. (2000) Patterns of cognitive ageing. Psychol. Res. 63, 308–316.

    Article  PubMed  CAS  Google Scholar 

  • Rapp P. R. and Amaral D. G. (1992) Individual differences in the cognitive and neurobiological consequences of normal aging. Trends Neurosci. 15, 340–345.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Salthouse T. A. (1990) Working memory as a processing resource in cognitive aging. Dev. Rev. 10, 101–124.

    Article  Google Scholar 

  • Salthouse T. A. (1992) Mechanisms of Age-Cognition Relations in Adulthood. Erlbaum, Hilsdale, N.J.

    Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Sherwin B. B. (1997) Estrogen effects on cognition in menopausal women. Neurology 48, S21-S26.

    PubMed  CAS  Google Scholar 

  • Sherwin B. B. and Phillips S. M. (1990) Estrogen and cognitive functioning in surgically menopausal women. Ann. N. Y. Acad. Sci. 592, 474–475.

    Article  Google Scholar 

  • Sherwin B. B. (1994) Estrogenic effects on memory in women. Ann. N. Y. Acad. Sci. 743, 213–230.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Sherwin B. B. (2003) Estrogen and cognitive functioning in women. Endocrine Rev. 24, 133–151.

    Article  CAS  Google Scholar 

  • Silverman I., Kastuk D., Choi J., and Phillips K. (1999). Testosterone levels and spatial ability in men. Psychoneuroendocrinology 24, 813–822.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Small S. A., Stern Y., Tang M., and Mayeux R. (1999a) Selective decline in memory function among healthy elderly. Neurology 52, 1392–1396.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Small S. A. (2001) Age-related memory decline: current concepts and future directions. Arch. Neurol. 58, 360–364.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Sternbach H. (1998) Age-associated testosterone decline in men: clinical issues for psychiatry. Am. J. Psychiatry 155, 1310–1318.

    PubMed  CAS  Google Scholar 

  • Svec F. and Lopez A. (1989) Antiglucocorticoid actions of dehydroepiandrosterone and low concentrations in Alzheimer’s disease. Lancet 2, 1335–1336.

    Article  PubMed  CAS  Google Scholar 

  • Taylor E. M. (1959) Psychological Appraisal of Children with Cerebral Defects. Harvard University Press, Cambridge, MA.

    Google Scholar 

  • Tenover J. S. (1992) Effects of testosterone supplementation in the aging male. J. Clin. Endocrinol. Metab. 75, 1092–1098.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychology and Department of OB/GYN, McGill University, Montreal, Canada

    Barbara B. Sherwin

Authors
  1. Barbara B. Sherwin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Barbara B. Sherwin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sherwin, B.B. Steroid hormones and cognitive functioning in aging men. J Mol Neurosci 20, 385–393 (2003). https://doi.org/10.1385/JMN:20:3:385

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/JMN:20:3:385

Index Entries

Search

Navigation