Older men with higher levels of free, or unbound, testosterone circulating in their bloodstreams have better visual and verbal recall and perform spatial tasks more adeptly than their peers, according to investigators at the National Institute on Aging (NIA). The study* identifies a potential biological factor that one day could be used to protect against decline in memory and other cognitive skills in later life.
"Although we can't firmly establish a causal relationship without further study, this finding suggests that there may be hormonal modulation of cognitive abilities as people get older. Clearly, having higher levels of circulating free testosterone is associated with a reduced risk of certain types of memory loss," said Susan Resnick, Ph.D., an investigator in the NIA's Laboratory of Personality and Cognition, and corresponding author of the study, published in the November 2002 issue of The Journal of Clinical Endocrinology & Metabolism .
Dr. Resnick, Scott Moffat, Ph.D., and their colleagues evaluated the testosterone levels of 407 men, ages 50 and older, who participated in the Baltimore Longitudinal Study of Aging (BLSA)**. The investigators then correlated free and total testosterone levels—measured over an average of 10 years--with the men's performances on memory and other cognitive tests.
In the body, testosterone tends to bind with sex hormone binding gobulin (SHBG). But some testosterone remains freely circulating in the bloodstream. Unlike the SHBG-bound form of the hormone, free testosterone can circulate into the brain and affect nerve cells, Dr. Resnick said. Total testosterone is a measure of both free and SHBG-bound forms of the hormone. Of these measures, only free testosterone was significantly associated with higher scores on verbal and visual memory tests, such as recalling word lists and drawing a recently seen image. Free testosterone was also linked to high scores on a spatial test in which participants were asked to determine if rotated shapes were the same or different.
"Based on our results, testosterone levels are associated with selective and very specific effects on some aspects of cognition, including memory," Dr. Resnick said.
In men, testosterone is produced in the testes, the reproductive glands that also produce sperm. As men age, their testes often produce somewhat less testosterone than they did during adolescence and early adulthood, when production of this hormone peaks.
Based on BLSA data, as many as 68 percent of men older than 70 have low levels of free testosterone. But while prescription testosterone replacement therapy is available, it may not be advisable for most older men because many effects of hormone supplementation remain unclear. It is not yet known, for instance, if testosterone replacement increases the risk of prostate cancer, the second leading cause of cancer death among men. In addition, studies suggest that supplementation might trigger excessive red blood cell production in some men. This side effect can thicken blood and increase a man's risk of stroke.
"We still have much to learn," Dr. Resnick said. "Until we know much more about the fundamental effects of sex hormones on the aging brain and other parts of the body, testosterone supplementation is not a prudent choice for older men seeking to improve their memory and cognitive performance."
*S.D. Moffat, A.B. Zonderman, E.J. Metter, M.R. Blackman, S.M. Harman, and S.M. Resnick, "Longitudinal Assessment of Serum Free Testosterone Concentration Predicts Memory Performance and Cognitive Status in Elderly Men," The Journal of Clinical Endocrinology & Metabolism , 2002; 87 (11): 5001-5007.
Launched in 1958, the BLSA is America's longest running scientific examination of human aging. Volunteers receive comprehensive medical, physiological and neuropsychological evaluations every two years at the NIA Gerontology Research Center in Baltimore. The BLSA has measured testosterone levels in its male participants since 1963.
The National Institute on Aging, one of 27 Institutes and Centers that constitute the National Institutes of Health, leads Federal efforts to support and conduct basic, clinical, epidemiological, and social research on aging and the special needs of older people. For more information about the NIA, visit the website at http://www.nia.nih.gov/.