Testosterone No Elixir for the Brain in Healthy Aging Men

Megan Brooks

July 12, 2016

Prescribing testosterone to relatively healthy older men with low or low to normal testosterone levels does not improve cognitive function and is not justified, new research suggests.

"Testosterone administration for 3 years to raise testosterone concentrations into a range that is mid-normal for healthy young men was not associated with improvement in any domain of cognitive function," Grace Huang, MD, of Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, and colleagues report.

The results are from a prespecified secondary analysis of data from the Testosterone Effects on Atherosclerosis in Aging Men (TEAAM) trial and were published online July 1 in the Lancet Diabetes and Endocrinology.

The original results from the TEAAM trial showed no significant rate of change in common carotid artery intima-media thickness or coronary artery calcium levels (coprimary outcomes), overall sexual function, or health-related quality of life in the testosterone group in comparison with the placebo group.

The prespecified analysis of cognitive function included 280 men aged 60 years and older with low or low to normal testosterone concentrations (3.47 to 13.9 nmol/L, or free testosterone < 173 pmol/L) and normal cognitive function who were randomly allocated to receive either 7.5 g of 1% testosterone gel or placebo gel for 3 years. The testosterone dose was adjusted to achieve concentrations of 17.3 to 31.2 nmol/L. Men receiving testosterone experienced androgenic effects consistent with overall compliance with daily testosterone gel application.

In men using testosterone gel, mean serum concentrations of total testosterone rose from 10.6 nmol/L to 19.7 nmol/L, and free testosterone concentrations increased from 222 pmol/L to 364 pmol/L. In contrast, men receiving placebo gel had no marked increase in serum total testosterone concentrations (10.7 nmol/L at baseline vs 11.1 nmol/L post intervention) or free testosterone concentraitons (210 pmol/L to 364 pmol/L).

Performance on a broad range of domains of cognitive function did not differ significantly between groups at any time point, after adjusting for age, education, and baseline cognitive function, the researchers report. In both the intention-to-treat and per-protocol populations, changes in cognitive function scores were not related significantly to changes in total or free testosterone concentrations or estradiol concentrations, they note.

"With an intervention duration of 3 years, our trial is one of the longest and largest randomized placebo-controlled trials so far of testosterone in older men," the authors say. Unlike other studies, multiple domains of cognitive function, including visuospatial ability, verbal memory, verbal fluency, attention, executive function, and manual dexterity, were assessed using a comprehensive battery of standardized neuropsychological tests, including measures known to be sensitive to gonadal steroids.

The data, the authors conclude, "do not support use of testosterone for improvement in cognitive function in older men with age-related decline in testosterone concentrations."

"These negative findings are the best evidence so far regarding the effect of testosterone treatment on cognition in asymptomatic, fairly healthy older men with low testosterone," write Bradley Anawalt, MD, and Stephanie Page, MD, PhD, of the University of Washington, Seattle, in a linked commentary. "For older men with clinically normal cognitive function, low to low-to-normal serum total testosterone concentrations, and no known cause for hypogonadism, testosterone treatment is not an elixir for the brain," they say.

In an interview with Medscape Medical News, Dr Page said the findings are not surprising given the characteristics of the men who were included in the study.

"They were highly educated and didn't have any cognitive dysfunction. This tells us is that if you supplement men with testosterone that are healthy otherwise, at least in terms of their cognitive function, that there aren't gains to be had," she said.

Dr Page also noted that "many men are being prescribed testosterone without adequate screening, for sort of unclear reasons. I think there is a notion out there that testosterone can be a panacea for a number of age-associated declines, and I think what this [study] tells us is that while testosterone may have some significant benefits for some individuals, it's not a panacea."

Several important clinical questions regarding testosterone and cognitive function were not addressed by this study, Dr Anawalt and Dr Page write in their commentary.

"First, what are the cognitive effects of testosterone treatment for men with known causes of hypogonadism, such as Klinefelter syndrome; second, does long-term testosterone treatment prevent cognitive impairment, decline, or dementia in young and middle-aged men with low serum testosterone concentrations; and third, what effects of testosterone are mediated via androgen effects and what are mediated via its metabolite, oestradiol?"

The study was supported by a grant from Solvay Pharmaceuticals and by AbbVie Pharmaceuticals (after AbbVie acquired the Androgel brand from Solvay Pharmaceuticals). Testosterone and placebo gels for the study were provided by Solvay Pharmaceuticals and later by AbbVie Pharmaceuticals. One investigator has received research grant support from AbbVie. Dr Page has disclosed no relevant financial relationships.

Lancet Diab Endocrinol. Published online July 1, 2016. Abstract, Commentary


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