This article is more than 5 years old. Information may no longer be current.
No difference in cognitive impairment seen in men on testosterone treatment
Click Here to Manage Email Alerts
One year of testosterone treatment did not improve memory or other cognitive functions compared with placebo among older men with low testosterone and age-associated memory impairment, according to study findings published in JAMA.
“Aging is associated with declines in some cognitive functions, including verbal and visual memory, executive function, and spatial ability,” Susan M. Resnick, PhD, from the laboratory of behavioral neuroscience at the NIH’s National Institute on Aging, and colleagues wrote. “Aging in men is also associated with a reduction in serum testosterone, raising the possibility that reduced circulating testosterone concentration may contribute to age-related cognitive decline.”
“Men with age-associated memory impairment (AAMI) represent a clinically important group at risk for developing more severe memory impairment (eg, mild cognitive impairment and dementia) for whom testosterone intervention may be beneficial,” they added.
Researchers sought to compare the efficacy of treatment with testosterone vs. placebo in improving verbal memory and other cognitive functions among older men with low testosterone and AAMI. They evaluated the cognitive function of older men with low testosterone due to age enrolled in the Testosterone Trials (TTrials). In their study, known as the Cognitive Function Trial, they examined 788 men who were aged 65 years or older with a serum testosterone level less than 275 ng/mL and impaired sexual function, physical function or vitality. A subgroup of 493 men met the criteria for AAMI. TTrial enrollment began June 24, 2010; the last participant completed treatment and evaluation in June 2014.
They assigned 394 participants to testosterone gel and 394 to placebo gel for 1 year to determine the mean change from baseline to 6 months and 12 months for delayed paragraph recall (score range, 0 to 50) among men with AAMI. Resnick and colleagues also evaluated changes in visual memory, executive function and spatial ability among men with AAMI.
Out of the 493 men with AAMI (mean baseline testosterone, 234 ng/dL), 247 receiving testosterone and 245 receiving placebo completed the memory study. The results showed no significant change from baseline to 6 and 12 months in delayed paragraph recall score among men with AAMI in both groups (adjusted estimated difference, –0.07; 95% CI, –0.92 to 0.79). The investigators found that in the testosterone group, mean scores for delayed paragraph recall were 14 at baseline, 16 at 6 months and 16.2 at 12 months compared with 14.4, 16 and 16.5 in the placebo group. They also observed no association between testosterone and significant differences in visual memory (–0.28; 95% CI, –0.76 to 0.19), executive function (–5.51; 95% CI, –12.91 to 1.88) or spatial ability (–0.12; 95% CI, –1.89 to 1.65).
“The lack of association between testosterone treatment and cognition was apparent across all cognitive domains assessed among men with AAMI, in spite of an increase in circulating total and free testosterone concentrations in the testosterone group to levels typical of men aged 19 to 40 years.” Resnick and colleagues wrote. “It is possible that a longer treatment duration could yield a different result.”
Other trials conducted as part of the NIH’s TTrials assessing the impact of testosterone supplementation identified several benefits from treatment. One study published in JAMA Internal Medicine reported that 1 year of testosterone treatment significantly increased volumetric bone mineral density and estimated bone strength in men aged 65 years and older. Another study found that older men with unexplained anemia can potentially benefit from measurement and treatment of testosterone levels Other research published in JAMA showed that testosterone treatment in older men was associated with a significantly greater increase in coronary artery noncalcified plaque volume. – by Savannah Demko
Disclosure: Resnick is an employee of National Institute of Aging/NIH. She reports receiving grants from NIA, NIH and AbbVie (Solvay & Abbott Lab. Please see the full study for a list of all other authors’ relevant financial disclosures.
Perspective
Back to Top
Alexander Kutikov, MD
The two manuscripts published in JAMA by the TTrials investigators deliver a double punch, but certainly not a knockout, for testosterone supplementation therapy. Both manuscripts focus on 1 year outcomes in a cohort of men aged older than 65 years who were randomized to a testosterone gel vs. placebo. One study reports on results of a theoretical benefit of the treatment, while the other evaluates a potential harm (Budoff MJ, et al. JAMA. 2017;doi:10.1001/jama.2016.21043). After 1 year of therapy, largely no difference in cognitive impairment was noted in men who were randomized to testosterone vs. placebo. These results held true both for men with and without age-associated memory impairments. Certainly 1 year of testosterone supplementation may not be a long enough time period to see either an improvement or prevention of decline in cognitive function in men with hypogonadism; however, 1 year of therapy appears to have been adequate to demonstrate arterial plaque build-up, as judged by the relatively novel technique of coronary CT angiography. Although at 1 year of follow-up this plaque build-up did not translate into a detectable difference in risk of coronary events; the findings are certainly concerning and provocative. Indeed, these data dovetail with nearly 2-decade-old data from the Heart and Estrogen/progestin Replacement Study (HERS) that suggested increased risk of cardiovascular events in women who received short-term hormone supplementation therapy.
When the risks appear real and the theoretical benefits prove ethereal, the choice to proceed with testosterone supplementation must be made with extreme care. The current manuscripts do not report on other purported benefits of testosterone supplementation such as improvement in overall well-being, enhancement in libido and sexual function, improved concentration, alleviation of depression, and even potential improvement in waist circumference and weight. Indeed, many of these potential benefits are often the primary drivers of testosterone therapy initiation in hypogonadal men. Until data regarding these outcome measures are reported, it may be difficult to stem the enthusiasm for testosterone supplementation in men who are convinced that their lack of energy and vigor stems from low levels of male hormone.
Read more about
Click Here to Manage Email Alerts