Intramuscular testosterone treatment in elderly men: Evidence of memory decline and altered brain function

Pauline M. Maki, Monique Ernst, Edythe D. London, Kristen L. Mordecai, Pamela Perschler, Samuel Durso, Jason Brandt, Adrian S Dobs, Susan M. Resnick

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4107-4114
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number11
DOIs
StatePublished - Nov 2007
Externally publishedYes

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Testosterone
Brain
Data storage equipment
Temporal Lobe
Positron emission tomography
Therapeutics
Positron-Emission Tomography
Placebos
Sesame Oil
Entorhinal Cortex
Amygdala
Prefrontal Cortex
Cross-Over Studies
Outcome Assessment (Health Care)
Clinical Trials
Glucose
Composite materials
Research
Population

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Intramuscular testosterone treatment in elderly men : Evidence of memory decline and altered brain function. / Maki, Pauline M.; Ernst, Monique; London, Edythe D.; Mordecai, Kristen L.; Perschler, Pamela; Durso, Samuel; Brandt, Jason; Dobs, Adrian S; Resnick, Susan M.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 92, No. 11, 11.2007, p. 4107-4114.

Research output: Contribution to journalArticle

Maki, Pauline M. ; Ernst, Monique ; London, Edythe D. ; Mordecai, Kristen L. ; Perschler, Pamela ; Durso, Samuel ; Brandt, Jason ; Dobs, Adrian S ; Resnick, Susan M. / Intramuscular testosterone treatment in elderly men : Evidence of memory decline and altered brain function. In: Journal of Clinical Endocrinology and Metabolism. 2007 ; Vol. 92, No. 11. pp. 4107-4114.
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abstract = "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.",
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AU - London, Edythe D.

AU - Mordecai, Kristen L.

AU - Perschler, Pamela

AU - Durso, Samuel

AU - Brandt, Jason

AU - Dobs, Adrian S

AU - Resnick, Susan M.

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N2 - 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.

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