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Original Investigation
February 21, 2017

Testosterone Treatment and Cognitive Function in Older Men With Low Testosterone and Age-Associated Memory Impairment

Author Affiliations
  • 1Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, Maryland
  • 2Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Puget Sound Health Care System, Seattle, Washington
  • 3Division of Gerontology and Geriatric Medicine, Department of Internal Medicine, University of Washington School of Medicine, Seattle
  • 4Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia
  • 5Division of Geriatric Medicine, Yale School of Medicine, New Haven, Connecticut
  • 6Wake Forest School of Medicine, Winston-Salem, North Carolina
  • 7Department of Internal Medicine and Division of Epidemiology, Department of Family Medicine and Public Health, University of California San Diego School of Medicine, La Jolla
  • 8Research Program in Men’s Health, Aging, and Metabolism, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 9Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
  • 10Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • 11Divisions of Endocrinology and Geriatrics, Albert Einstein College of Medicine, Bronx, New York
  • 12Departments of Medicine and Molecular and Cellular Biology, Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, Texas
  • 13Baylor St Luke's Medical Center, Houston, Texas
  • 14Department of Medicine, Division of Epidemiology and Community Health, University of Minnesota, Minneapolis
  • 15Minneapolis Veterans Affairs Health Care System. Minneapolis, Minnesota
  • 16Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia
  • 17Division of Preventive Medicine, University of Alabama at Birmingham
  • 18Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • 19Department of Aging and Geriatric Research, University of Florida, Gainesville
  • 20Division of Endocrinology, Harbor-University of California at Los Angeles Medical Center, Torrance
  • 21Los Angeles Biomedical Research Institute, Torrance, California
  • 22Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia
JAMA. 2017;317(7):717-727. doi:10.1001/jama.2016.21044
Key Points

Question  Is treatment with testosterone for 1 year associated with improved memory in older men with low testosterone and age-associated memory impairment?

Findings  In this placebo-controlled study of 788 older men with symptomatic hypogonadism, 493 had age-associated memory impairment, defined by subjective memory complaints and impaired performance on tests of verbal and visual memory. Compared with placebo, 1 year of testosterone treatment was not significantly associated with improved memory or other cognitive functions in these men.

Meaning  This study does not support the use of testosterone for the treatment of age-associated memory decline in older men with symptomatic hypogonadism.


Importance  Most cognitive functions decline with age. Prior studies suggest that testosterone treatment may improve these functions.

Objective  To determine if testosterone treatment compared with placebo is associated with improved verbal memory and other cognitive functions in older men with low testosterone and age-associated memory impairment (AAMI).

Design, Setting, and Participants  The Testosterone Trials (TTrials) were 7 trials to assess the efficacy of testosterone treatment in older men with low testosterone levels. The Cognitive Function Trial evaluated cognitive function in all TTrials participants. In 12 US academic medical centers, 788 men who were 65 years or older with a serum testosterone level less than 275 ng/mL and impaired sexual function, physical function, or vitality were allocated to testosterone treatment (n = 394) or placebo (n = 394). A subgroup of 493 men met criteria for AAMI based on baseline subjective memory complaints and objective memory performance. Enrollment in the TTrials began June 24, 2010; the final participant completed treatment and assessment in June 2014.

Interventions  Testosterone gel (adjusted to maintain the testosterone level within the normal range for young men) or placebo gel for 1 year.

Main Outcomes and Measures  The primary outcome was the mean change from baseline to 6 months and 12 months for delayed paragraph recall (score range, 0 to 50) among men with AAMI. Secondary outcomes were mean changes in visual memory (Benton Visual Retention Test; score range, 0 to −26), executive function (Trail-Making Test B minus A; range, −290 to 290), and spatial ability (Card Rotation Test; score range, −80 to 80) among men with AAMI. Tests were administered at baseline, 6 months, and 12 months.

Results  Among the 493 men with AAMI (mean age, 72.3 years [SD, 5.8]; mean baseline testosterone, 234 ng/dL [SD, 65.1]), 247 were assigned to receive testosterone and 246 to receive placebo. Of these groups, 247 men in the testosterone group and 245 men in the placebo completed the memory study. There was no significant mean change from baseline to 6 and 12 months in delayed paragraph recall score among men with AAMI in the testosterone and placebo groups (adjusted estimated difference, −0.07 [95% CI, −0.92 to 0.79]; P = .88). Mean scores for delayed paragraph recall were 14.0 at baseline, 16.0 at 6 months, and 16.2 at 12 months in the testosterone group and 14.4 at baseline, 16.0 at 6 months, and 16.5 at 12 months in the placebo group. Testosterone was also not associated with significant differences in visual memory (−0.28 [95% CI, −0.76 to 0.19]; P = .24), executive function (−5.51 [95% CI, −12.91 to 1.88]; P = .14), or spatial ability (−0.12 [95% CI, −1.89 to 1.65]; P = .89).

Conclusions and Relevance  Among older men with low testosterone and age-associated memory impairment, treatment with testosterone for 1 year compared with placebo was not associated with improved memory or other cognitive functions.

Trial Registration  clinicaltrials.gov Identifier: NCT00799617