Aging Men, Obesity, Metabolic Syndrome, Decrease in Total Serum Testosterone Levels

Researchers writing in the Journal of Urology say that their study “…demonstrated that aging men with obesity and the metabolic syndrome have a significant decrease in total serum testosterone levels compared to aging, metabolically healthy men.”

Kaplan SA, Meehan AG, Shah A. The Age Related Decrease in Testosterone is Significantly Exacerbated in Obese Men With the Metabolic Syndrome. What are the Implications for the Relatively High Incidence of Erectile Dysfunction Observed in These Men? J Urol. 2006 Oct;176(4):1524-8
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Testosterone and Cognitive Function

A study in the European Journal of Endocrinology says “Low endogenous levels of testosterone may be related to reduced cognitive ability, and testosterone substitution may improve some aspects of cognitive ability.”

Beauchet O. Testosterone and cognitive function: current clinical evidence of a relationship. Beauchet O. Eur J Endocrinol. 2006 Dec;155(6):773-81.

BACKGROUND: Testosterone levels decline as men age, as does cognitive function. Whether there is more than a temporal relationship between testosterone and cognitive function is unclear. Chemical castration studies in men with prostate cancer suggest that low serum testosterone may be associated with cognitive dysfunction. Low testosterone levels have also been observed in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI). This paper reviews the current clinical evidence of the relationship between serum testosterone levels and cognitive function in older men.

METHODS: A systematic literature search was conducted using PubMed and EMBASE to identify clinical studies and relevant reviews that evaluated cognitive function and endogenous testosterone levels or the effects of testosterone substitution in older men.

RESULTS: Low levels of endogenous testosterone in healthy older men may be associated with poor performance on at least some cognitive tests. The results of randomized, placebo-controlled studies have been mixed, but generally indicate that testosterone substitution may have moderate positive effects on selective cognitive domains (e.g. spatial ability) in older men with and without hypogonadism. Similar results have been found in studies in patients with existing AD or MCI.

CONCLUSIONS: Low endogenous levels of testosterone may be related to reduced cognitive ability, and testosterone substitution may improve some aspects of cognitive ability. Measurement of serum testosterone should be considered in older men with cognitive dysfunction. For men with both cognitive impairment and low testosterone, testosterone substitution may be considered. Large, long-term studies evaluating the effects of testosterone substitution on cognitive function in older men are warranted.

Low Testosterone Levels and Mortality

Researchers writing in the Annals of Internal Medicine examined “whether low testosterone levels are a risk factor for mortality in male veterans.”

Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans.
Arch Intern Med. 2006 Aug 14-28;166(15):1660-5.

BACKGROUND: Low serum testosterone is a common condition in aging associated with decreased muscle mass and insulin resistance. This study evaluated whether low testosterone levels are a risk factor for mortality in male veterans.

METHODS: We used a clinical database to identify men older than 40 years with repeated testosterone levels obtained from October 1, 1994, to December 31, 1999, and without diagnosed prostate cancer. A low testosterone level was a total testosterone level of less than 250 ng/dL (<8.7 nmol/L) or a free testosterone level of less than 0.75 ng/dL (<0.03 nmol/L). Men were classified as having a low testosterone level (166 [19.3%]), an equivocal testosterone level (equal number of low and normal levels) (240 [28.0%]), or a normal testosterone level (452 [52.7%]). The risk for all-cause mortality was estimated using Cox proportional hazards regression models, adjusting for demographic and clinical covariates over a follow-up of up to 8 years. RESULTS: Mortality in men with normal testosterone levels was 20.1% (95% confidence interval [CI], 16.2%-24.1%) vs 24.6% (95% CI, 19.2%-30.0%) in men with equivocal testosterone levels and 34.9% (95% CI, 28.5%-41.4%) in men with low testosterone levels. After adjusting for age, medical morbidity, and other clinical covariates, low testosterone levels continued to be associated with increased mortality (hazard ratio, 1.88; 95% CI, 1.34-2.63; P<.001) while equivocal testosterone levels were not significantly different from normal testosterone levels (hazard ratio, 1.38; 95% CI, 0.99%-1.92%; P=.06). In a sensitivity analysis, men who died within the first year (50 [5.8%]) were excluded to minimize the effect of acute illness, and low testosterone levels continued to be associated with elevated mortality.

CONCLUSIONS: Low testosterone levels were associated with increased mortality in male veterans. Further prospective studies are needed to examine the association between low testosterone levels and mortality.