testosterone replacement

In males, testosterone is produced by the testes and is involved in sperm production, male-related physical changes, and cognitive functions. Several studies indicate that higher testosterone levels are associated with better cognition. Unfortunately, testosterone concentration gradually decreases after the age of 30-35, and there is concern of potential cognitive impairments. To this end, a recent report demonstrated that testosterone replacement failed to improve cognition in cognitively normal men aged 60 or older with low or low-to-normal testosterone levels.


Testosterone is the main sex hormone produced in the testes of males. It is responsible for the production of male gametes (sperm), cognitive functions, and male-related physical changes at puberty including deepening of the voice, male hair pattern, building of muscles, and bone strength. Circulating testosterone levels gradually decrease after the age of thirty. This age-related decline of testosterone has been associated with impaired cognitive abilities in older men. Therefore, researchers are interested in determining whether testosterone replacement could potentially prevent or even reverse the cognitive impairments that arise due to low testosterone levels. In fact, epidemiological studies have demonstrated that higher concentrations of testosterone are associated with improved cognitive functioning in older men. Moreover, cross-sectional studies have shown that patients with Alzheimer’s (impaired cognitive functions) have lower testosterone levels than healthy males. However, the few studies investigating the role of testosterone replacement in improving cognitive functions have been inconsistent, where some studies have reported improvements while others show no benefit at all.

A recent report published in The Lancet – Diabetes and Endocrinology aimed at establishing the effects of long-term testosterone administration on cognitive functions in older men with low or low-to-normal testosterone concentrations. The studied consisted of 308 cognitively normal men aged 60 or older with low or low-to-normal testosterone levels. 156 participants were given a testosterone gel daily for 36 months, while the remaining 152 men were given a placebo. Cognitive analyses were conducted at baseline, 6, 18, and 36 months using validated neuropsychological tests for visuospatial ability, verbal memory, verbal fluency, attention and executive function, and manual dexterity. Baseline testosterone measurements were similar between the two groups, however, these levels increased for the testosterone-treated group at 6, 18, and 36 months. Additionally, baseline cognitive measurements were the same for the two groups after adjustments for age, race, and education. Interestingly, however, there was no improvement in cognitive function after 36 months in either of the groups, suggesting that testosterone therapy had no effect in improving cognitive function in older, cognitively normal men.

In the longest and largest study to date, researchers demonstrated that testosterone administration over a course of 36 months in cognitively normal men over the age of 60 had no improvement in cognitive functions. Currently in the literature, there is a lot of discrepancy and confusion in regards to the potential role of testosterone replacement on cognition. Some studies, including the one reported, demonstrate no improved cognitive functions, while others have shown improvements. The differences in results could arise due to several factors including differences in cognitive tests, variable time-frames, and differences in exogenous versus endogenous testosterone hormone. Moreover, the current study investigated cognitively competent men, and it could be possible that the therapeutic effects are only observable in men with significant cognitive deficits or in men with significantly low testosterone levels. In conclusion, the study was unable to show beneficial effects of testosterone therapy, and therefore, testosterone replacement is not recommended in older, cognitively normal men with low or low-to-normal testosterone levels. Moving forward, it would be beneficial to test the effect of testosterone in cognitively deficient men.




Written By: Haisam Shah, BSc

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