Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-15T15:30:55.172Z Has data issue: false hasContentIssue false

The Effects of Testosterone on Cognition in Elderly Men: A Review

Published online by Cambridge University Press:  07 November 2014

Abstract

In this article, the literature examining the relationship between testosterone and various cognitive domains in elderly men is reviewed. The review focuses on the role of endogenous testosterone levels and the effects of androgen depletion and replacement. The cognitive domains most commonly linked to testosterone include memory and visuospatial function. Indeed, the literature suggests that in certain conditions (ie, hypogonadism, cognitive impairment) testosterone levels may be significantly associated with memory and visuospatial function, but not other cognitive functions. Studies with larger sample sizes and more sensitive cognitive measures are indicated, as questions remain about the potential role of testosterone as a cognitive enhancer.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Beauchet, O. Testosterone and cognitive function: current clinical evidence of a relationship. Eur J Endocrinol. 2006;155:773781.CrossRefGoogle ScholarPubMed
2.Leifke, E, Gorenoi, V, Wichers, C, Von Zur Muhlen, A, Von Buren, E, Brabant, G. Age related changes of serum sex hormones, insulin like growth factor 1 and sex-hormone binding globulin levels in men: cross sectional data from a healthy male cohort. Clin Endocrinol. 2000;53:689695.CrossRefGoogle ScholarPubMed
3.Moffat, SD, Zonderman, AB, Metter, EJ, Blackman, MR, Harman, SM, Resnick, SM. Longitudinal assessment of serum free testosterone concentrations predicts memory performance and cognitive status in elderly men. J Clin Endocrinol Metab. 2002;87:50015007.Google Scholar
4.Leranth, C, Petnehazy, O, MacLusky, NJ. Gonadal hormones affect spine synaptic density in the CA1 hippocampal subfield of male rats. J Neurosci. 2003;23:15881592.CrossRefGoogle ScholarPubMed
5.Leranth, C, Prange-Kiel, J, Frick, KM, Horvath, TL. Low CA1 spine synapse density is further reduced by castration in male non-human primates. Cereb Cortex. 2004;14:503510.Google Scholar
6.MacLusky, NJ, Hajszan, T, Prange-Kiel, J, Leranth, C. Androgen modulation of hippocampal plasticity. Neuroscience. 2006;138:957965.Google Scholar
7.Hajszan, T, MacLusky, NJ, Johansen, JA, Jordan, CL, Leranth, C. Effects of androgens and estradiol on spine synapse formation in the prefrontal cortex of normal and testicular feminization mutant male rats. Endocrinol. 2007;148:19631967.Google Scholar
8.Frye, CA, Park, D, Tanaka, M, Rosellini, R, Svare, B. The testosterone metabolite and neurosteroid 3alpha-androstanediol may mediate the effects of testosterone on conditioned place preference. Psychoneuroendocrinology. 2001;26:731750.CrossRefGoogle ScholarPubMed
9.Bimonte-Nelson, HA, Singleton, RS, Nelson, ME, et al.Testosterone, but not nonaromatizable dihydro testosterone, improves working memory and alters nerve growth factor levels in aged male rats. Exp Neurol. 2003;181:301312.CrossRefGoogle ScholarPubMed
10.Barrett-Conner, E, Goodman-Gruen, D, Patay, B. Endogenous sex hormones and cognitive function in older men. J Clin Endocrinol Metab. 1999;84:36813685.Google Scholar
11.Thilers, PP, MacDonald, SWS, Herlitz, A. The association between endogenous free testosterone and cognitive performance: a population-based study in 35 to 90 year-old men and women. Psychoneuroendocrinology. 2006;31:565576.Google Scholar
12.Fonda, SJ, Bertrand, R, O'Donnell, A, Longcope, C, McKinlay, JB. Age, hormones and cognitive functioning among middle age and elderly men: cross-sectional evidence from the Massachusetts Male Aging Study. J Gerontol A Biol Sci Med Sci. 2005;60:385390.Google Scholar
13.Lessov-Schlagar, CN, Reed, T, Swan, GE, et al.Association of sex steroid hormones with brain morphology and cognition in healthy elderly men. Neurology. 2005;65:15911596.Google Scholar
14.Yaffe, K, Barnes, D, Lindquist, K, et al.Endogenous sex hormone levels and risk of cognitive decline in an older biracial cohort. Neurobiol Aging. 2007;28:171178.Google Scholar
15.Wolf, OT, Kirschbaum, C. Endogenous estradiol and testosterone levels are associated with cognitive performance in older women and men. Horm Behav. 2000;41:259266.Google Scholar
16.Almeida, OP, Waterreus, A, Spry, N, Flicker, L, Martins, RN. One year follow-up study of the association between chemical castration, sex hormones, beta-amyloid, memory and depression in men. Psychoneuroendocrinology. 2004;29:10711081.Google Scholar
17.Bussiere, JR, Beer, TM, Neiss, MB, Janowsky, JS. Androgen deprivation impairs memory in older men. Behav Neurosci. 2005;119:14291437.Google Scholar
18.Beer, TM, Bland, LB, Bussiere, JR, et al.Testosterone loss and estradiol administration modify memory in men. J Urol. 2006;175:130135.Google Scholar
19.Green, HJ, Pakenham, KI, Headley, BC, et al.Altered cognitive function in men treated for prostate cancer with luteinizing hormone-releasing hormone analogues and cyproterone acetate: a randomized controlled trial. BJU Int. 2002;90:427432.Google Scholar
20.Janowsky, JS, Cahvez, B, Orwoll, E. Sex steroids modify working memory. J Cogn Neurosci. 2000;12:407414.Google Scholar
21.Muller, M, Aleman, A, Grobbee, DE, de Hann, EH, van der Schouw, YT. Endogenous sex hormone levels and cognitive functioning in aging men: is there an optimal level? Neurology. 2005;64:866871.Google Scholar
22.Cherrier, MM, Asthana, S, Plymate, S, et al.Testosterone supplementation improves spatial and verbal memory in healthy older men. Neurology. 2001;57:8088.CrossRefGoogle ScholarPubMed
23.Cherrier, MM, Matsumoto, AM, Amory, JK, et al.Testosterone improves spatial memory in men with Alzheimer's disease and mild cognitive impairment. Neurology. 2005;64:26032608.Google Scholar
24.Cherrier, MM, Matsumoto, AM, Armory, JK, et al.Characterization of verbal and spacial memory changes from moderate to supraphysiological increases in serum testosterone in healthy older men. Psychoneuroendocrinology. 2007;32:7279.Google Scholar
25.Emmelot-Vonk, MH, Verhaar, HJJ, Nakhai Pour, HR, et al.Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men. JAMA. 2008;299:3952.Google Scholar
26.Yonker, JE, Eriksson, E, Lars-Goran, N, Herlitz, A. Negative association of testosterone on spatial visualization in 35 to 80 year old men. Cortex. 2006;42:376386.Google Scholar
27.Yaffe, K, Lui, LY, Zmuda, J, Cauley, J. Sex hormones and cognitive function in older men. J Am Geriatric Soc. 2002;50:707712.Google Scholar
28.Hogervorst, E, De Jager, C, Budge, M, Smith, AD. Serum levels of estradiol and testosterone and performance in different cognitive domains in healthy elderly men and women. Psychoneuroendocrinology. 2004;29:405421.Google Scholar
29.Lu, PH, Masterman, DA, Mulnard, R, et al.Effects of testosterone on cognition and mood in male patients with mild Alzheimer disease and healthy elderly men. Arch Neurol. 2006;63:177185.Google Scholar
30.Vaughan, C, Goldstein, FC, Tenover, JL. Exogenous testosterone alone or with finasteride does not improve measurements of cognition in healthy older men with low serum testosterone. J Androl. 2007;28:875882.Google Scholar
31.Sih, R, Morley, JE, Kaiser, FE, Perry, HM 3rd, Patrick, P, Ross, C. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab. 1997;82:16611667.CrossRefGoogle Scholar
32.Janowsky, J. Thinking with your gonads: testosterone and cognition. Trends Cogn Sci. 2006;10:7782.Google Scholar
33.Cherrier, MM, Rose, AL, Higano, C. The effects of combined androgen blockade on cognitive function during the first cycle of intermittent androgen suppression in patients with prostate cancer. J Urol. 2003;170:18081811.CrossRefGoogle ScholarPubMed
34.Cherrier, MM, Matsumoto, AM, Amory, JK, et al.The role of aromatization in testosterone supplementation: effects on cognition in older men. Neurology. 2005;64:290296.Google Scholar
35.Tan, RS, Pu, SJ. A pilot study on the effects of testosterone in hypogonadal aging male patients with Alzheimer's disease. Aging Male. 2003;6:1317.Google Scholar
36.Kenny, AM, Fabregas, G, Song, C, Biskup, B, Bellantonio, S. Effects of testosterone on behavior, depression and cognitive function in older men with mild cognitive loss. J Gerontol A Biol Sci Med Sci. 2004;59A:7578.Google Scholar
37.Kenny, AM, Bellantonio, S, Gruman, CA, Acosta, RD, Prestwood, KM. Effects of transdermal testosterone on cognitive function and health perception in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci. 2002;57:M321M325.CrossRefGoogle ScholarPubMed
38.Haren, MT, Wittert, GA, Chapman, IM, Coates, P, Morley, JE. Effect of testosterone undecanoate on visuospatial cognition, mood and quality of life in elderly men with low-normal gonadal status. Maturitas. 2005;50:124133.Google Scholar
39.Janowsky, JS, Oviatt, SK, Orwoll, ES. Testosterone influences spatial cognition in older men. Behav Neuroscience. 1994;108:325332.Google Scholar
40.Meethal, SV, Smith, MA, Bowen, RL, Atwood, CS. The gonadotropin connection in Alzheimer's disease. Endocrine. 2005;26:317326.Google Scholar
41.Bowen, RL, Smith, MA, Harris, PL, et al.Elevated luteinizing hormone expression colocalizes with neurons vulnerable to Alzheimer's disease pathology. J Neurosci Res. 2002;70:514518.Google Scholar
42.Moffat, SD. Effects of testosterone on cognitive and brain aging in elderly men. Ann N Y Acad Sci. 2005;1055:8092.Google Scholar
43.Abdelgadir, SE, Roselli, CE, Choate, JV, Resko, JA. Androgen receptor messenger ribonucleic acid in brains and pituitaries of male mesus monkeys: studies on distribution, hormonal control, and relationship to luteinizing hormone secretion. Biol Reprod. 1999;60:12511256.Google Scholar
44.Kritzer, M. The distribution of immunoreactivity for intracellular androgen receptors in the cerebral cortex of hormonally intact adult male and female rats: localization in pyramidal neurons making corticocortical connections. Cereb Cortex. 2004;14:268280.Google Scholar
45.Puy, L, Maclusky, NJ, Becker, L, Karsan, N, Trachtenberg, J, Brown, JT. Immunocytochemical detection of androgen receptor in human temporal cortex characterization and application of polyclonal androgen receptor antibodies in frozen and paraffin-embedded tissues. J Steroid Biochem Mol Biol. 1995;55:197209.Google Scholar
46.Kimura, D. Sex and Cognition. Cambridge, Mass; MIT Press; 1999.Google Scholar
47.Cherrier, MM. Androgens and cognitive function. J Endocrinol Invest. 2005;28:6575.Google ScholarPubMed
48.Galea, LA, Kimura, D. Sex differences in route learning. Person Individ Diff. 1993;14:5365.Google Scholar
49.McBurney, DH, Gaulin, SJC, Devineni, T, Adams, C. Superior spatial memory of women: stronger evidence of the gathering. Evol Hum Behav. 1997;18:165174.Google Scholar
50.Eals, M, Silverman, I. The hunter gatherer theory of spatial sex differences: proximate factors. Ethol Sociobiol. 1994;15:95105.CrossRefGoogle Scholar
51.Shelton, AL, Gabrieli, JD. Neural correlates of encoding space from route and survey perspectives. J Neurosci. 2002;22:27112717.CrossRefGoogle ScholarPubMed
52.Cherrier, MM, Rose, AL, Higano, C. The effects of combined androgen blockade on cognitive function during the first cycle of intermittent androgen suppression in patients with prostate cancer. J Urol. 2003;170:18081811.Google Scholar
53.Moffat, SD, Zonderman, AB, Metter, EJ, et al.Free testosterone and risk for Alzheimer disease in older men. Neurology. 2004;62:188193.Google Scholar
54.Hogervorst, E, Bandelow, S, Moffat, SD. Increasing testosterone levels and effects on cognitive functions in elderly men and women: a review. Curr Drug Targets CNS Neurol. Disord. 2005;5:531540.CrossRefGoogle Scholar