Clinical Question

Does supplemental testosterone improve cognitive function in memory-impaired older men with low testosterone levels?

Bottom Line

Testosterone supplementation for men 65 years or older with age-associated memory impairment and a low baseline testosterone level was not associated with significant improvements in memory or other cognitive functions. (Level of Evidence = 1b)

Synopsis

These investigators recruited adult men, 65 years or older, with a mean of two morning serum testosterone concentrations of less than 275 ng per dL (9.5 nmol per L). Exclusion criteria included significant cognitive impairment (Mini-Mental State Examination score < 24) and severe depression. Age-associated memory impairment was classified as subjective memory concerns and relative memory impairment (defined as more than one standard deviation below the performance scores for men 20 to 24 years of age, but not greater than two standard deviations below the scores of age-matched men) on a standard scoring tool. A total of 493 men randomly received (concealed allocation assignment) testosterone gel, 1% concentration, at an initial dosage of 5 g daily or matched placebo. The dosage of testosterone was adjusted by an unmasked study investigator to achieve a level within the mid-normal range for young men (500 to 800 ng per dL [17.4 to 27.8 nmol per L]). To maintain participant and treating-clinician masking, the dosage of placebo gel was also adjusted simultaneously. Individuals masked to treatment group assignment assessed outcomes. Complete follow-up occurred for 97.3% of participants at 12 months.

Using intention-to-treat analyses, there were no significant improvements between the testosterone and control group on measurements of delayed paragraph recall scores, visual memory, executive function, or spatial ability.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (specialty)

Reference: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.