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From the Departments of Psychiatry and Behavioral Sciences (Drs. Cherrier, Baker, Peskind, Raskind, A. Petrova, and S. LaTendresse) and Medicine (Drs. Bremner, Asthana, Plymate, Matsumoto, and Brodkin), University of Washington Medical School, Seattle; Geriatric Research, Education, and Clinical Center (Drs. Cherrier, Asthana, Plymate, Baker, Matsumoto, Peskind, Brodkin, and Craft) and Mental Illness Research, Education, and Clinical Center (Drs. Peskind and Raskind), Veterans Administration Puget Sound Health Care System, Seattle, WA.
Address correspondence and reprint requests to Dr. Monique M. Cherrier, Department of Psychiatry, Box 356560, University of Washington Medical School, 1959 NE Pacific, Seattle, WA 98195; e-mail: cherrier{at}u.washington.edu
OBJECTIVE: To determine the relationship between exogenous testosterone administration and cognitive abilities in a population of healthy older men.
BACKGROUND: Serum levels of total and bioavailable testosterone gradually decrease with age in men and are associated with reductions in muscle mass, osteoporosis, decreased sexual activity, and changes in cognition.
METHODS: Twenty-five healthy, community-dwelling volunteers, aged 50 to 80 years, completed a randomized, double-blind, placebo-controlled study. Participants received weekly intramuscular injections of either 100 mg testosterone enanthate or placebo (saline) for 6 weeks. Cognitive evaluations were conducted at baseline, week 3, and week 6 of treatment by use of a battery of neuropsychologic tests.
RESULTS: Circulating total testosterone was raised an average of 130% from baseline at week 3 and 116% at week 6 in the treatment group. Because of aromatization of testosterone, estradiol increased an average of 77% at week 3 and 73% at week 6 in the treatment group. Significant improvements in cognition were observed for spatial memory (recall of a walking route), spatial ability (block construction), and verbal memory (recall of a short story) in older men treated with testosterone compared with baseline and the placebo group, although improvements were not evident for all measures.
CONCLUSIONS: The results suggest that short-term testosterone administration enhances cognitive function in healthy older men. However, it remains unclear whether these improvements in cognition are attributable to increased testosterone or estradiol levels, or both. The potential role of testosterone vs its metabolites on cognition requires further research.
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