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The role of aromatization in testosterone supplementation

Effects on cognition in older men

From the Department of Psychiatry and Behavioral Sciences (Drs. Cherrier, Peskind, Raskind, and Craft, M. Johnson), Department of Medicine (Drs. Matsumoto, Amory, and Bremner), and Division of Gerontology and Geriatric Medicine (Drs. Matsumoto and Ahmed), University of Washington Medical School, Seattle; and Geriatric Research, Education, and Clinical Center (Drs. Matsumoto, Peskind, Raskind, and Craft) and Mental Illness Research, Education, and Clinical Center (Drs. Cherrier, Peskind, and Raskind, M. Johnson), Veterans Administration Puget Sound Health Care System, Seattle, WA.

Address correspondence and reprint requests to Dr. Monique M. Cherrier, S-116 MIRECC VAPSHCS, 1660 South Columbian Way, Seattle, WA 98108; e-mail: cherrier{at}u.washington.edu

Objective: To determine the contribution of conversion of testosterone (T) to estradiol on cognitive processing in a population of healthy older men who received T supplementation.

Methods: Sixty healthy, community-dwelling volunteers aged 50 to 90 years completed a randomized, double-blind, placebo-controlled study. Participants were randomized to receive weekly IM injections of 100 mg T enanthate plus daily oral placebo pill (T group, n = 20), 100 mg testosterone enanthate plus 1 mg daily of anastrozole, an aromatase inhibitor (oral pill), to block the conversion of T to estradiol (AT group, n = 19), or saline injection and placebo pill (placebo group, n = 21) for 6 weeks. Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline, week 3 and week 6 of treatment, and after 6 weeks of washout.

Results: Circulating total T was increased from baseline an average of 238% in the T and AT treatment groups. Estradiol increased an average of 81% in the T group and decreased 50% in the AT group during treatment. Significant improvements in spatial memory were evident in the AT and T treatment groups. However, only the group with elevated estradiol levels (T group) demonstrated significant verbal memory improvement.

Conclusion: In healthy older men, improvement in verbal memory induced by testosterone administration depends on aromatization of testosterone to estradiol, whereas improvement in spatial memory occurs in the absence of increases in estradiol.

Supported in part by NIA award K01 AG00858, American Federation for Aging Research, Veterans Administration Puget Sound Health Care System and Clinical Research Center Facility at the University of Washington, and NIH M01-RR-00037.

Received June 11, 2004. Accepted in final form September 22, 2004.

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