This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Maki, P. M. Articles by Resnick, S. M. Search for Related Content PubMed PubMed Citation Articles by Maki, P. M. Articles by Resnick, S. M. Related Collections Neuroendocrinology and Pituitary Male Endocrinology

Intramuscular Testosterone Treatment in Elderly Men: Evidence of Memory Decline and Altered Brain Function

Center for Cognitive Medicine, Neuropsychiatric Institute, University of Illinois at Chicago, Chicago, Illinois 60612

Address all correspondence and requests for reprints to: Pauline M. Maki, Center for Cognitive Medicine, Neuropsychiatric Institute MC 913, University of Illinois at Chicago, 912 South Wood Street, Chicago, Illinois 60612. E-mail: pmaki{at}psych.uic.edu.

Context: Recent clinical trials of im testosterone in eugonadal men suggest positive effects on verbal memory, but other studies find no effect.

Objective: Our objective was to determine whether supraphysiological testosterone influences verbal memory and brain function during a verbal memory task in healthy eugonadal older men.

Patients, Design, and Setting: Fifteen cognitively normal men, aged 66–86 yr, participated in a randomized, double-blind, placebo-controlled crossover trial involving 9 months of participation per participant at a hospital-based research facility.

Intervention: We used testosterone enanthate (200 mg im every other week for 90 d) crossed over with placebo (sesame oil vehicle im) with a 90-d washout between treatments.

Main Outcome Measures: Performance was assessed on a standardized verbal memory test, and brain activity (relative glucose metabolic rates) in medial temporal and frontal regions was measured with positron emission tomography during a verbal memory task.

Results: Treatment increased total testosterone by 241%. Behavioral results showed a significant decrease in short-delay verbal memory with treatment (P < 0.05, effect size = 0.59 SD) and a nonsignificant decrease on a composite verbal memory measure (P = 0.09, effect size = 0.48 SD). Positron emission tomography scans revealed decreased relative activity in ventromedial temporal cortex (i.e. right amygdala/entorhinal cortex) and increased relative activity in bilateral prefrontal cortex with treatment.

Conclusions: Decreased verbal memory and altered relative activity in medial temporal and prefrontal regions suggest possible detrimental effects of supraphysiological testosterone supplementation in elderly men. The results do not rule out potential benefits with other regimens, cognitive tests, or populations.