Men older than 65 who have age-related memory impairment and testosterone deficiency do not experience improvement in cognitive performance with a year of testosterone replacement therapy (TRT), a new study finds.

“In spite of previously reported associations between testosterone and verbal memory, the results of this Cognitive Function Trial offer no support for a benefit to memory and little or no support for a benefit to other cognitive functions in older hypogonadal men, Susan M. Resnick, PhD, and colleagues wrote in the Journal of the American Medical Association.

Cognitive functions as well as testosterone levels typically decline with aging. Previous studies have suggested that TRT might improve some functions, including verbal and visual memory, executive function, and spatial perception. Verbal recall involves the hippocampus, which contains androgen receptors, for example.

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The investigators evaluated these specific outcomes in 493 men (mean age 72.3 years) with age-associated memory impairment, half of whom were randomly assigned to 1 year of TRT (testosterone gel 1%) and the other half to placebo. All of the men had hypogonadism symptoms and low testosterone levels (mean testosterone at baseline, 234 ng/dL). The investigators defined age-related memory impairment as subjective memory complaints along with subpar performance on objective tests of verbal and visual memory.

Results showed no significant change in the ability to recall a spoken paragraph after a time lapse. Average scores for delayed paragraph recall were 14.0, 16.0, and 16.2 at baseline, 6 months, and 12 months, respectively, for the TRT group compared with 14.4, 16.0, and 16.5 for the placebo group at the same time points. Men treated with TRT also had no significant improvement in visual memory, executive function, or spatial ability, based on a battery of well-chosen tests.

The researchers acknowledged that the study examined only 1 year of TRT. TRT also was administered as testosterone gel to provide a stable physiologic level, increasing circulating total and free testosterone levels to the midrange of normal for younger men (aged 19 to 40) which is 500 to 800 ng/dL. The gel method and dose (initially 5 g daily, then adjusted) did not spike testosterone levels as found in previous trials of injectable TRT, which may be a relevant factor in the results.

Importantly, men taking TRT were more likely to develop erythrocytosis, overly high hemoglobin levels at or above 17.5 g/dL.

The Cognitive Function Trial was one of 7 testosterone trials recommended by the Institute of Medicine in 2003 to identify possible benefits of TRT in hypogonadal older men. Results from related TRT trials on anemia and bone mineral density simultaneously were released by the journal.

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1. Resnick SM, Matsumoto AM, Stephens-Shields AJ, et al. Testosterone Treatment and Cognitive Function in Older Men With Low Testosterone and Age-Associated Memory Impairment. JAMA. 2017;317(7):717-727. doi:10.1001/jama.2016.21044