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Testosterone Treatment and Cognitive Function in Older Men With Low Testosterone and Age-Associated Memory Impairment
Open accessAbstract
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.
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“Though testosterone therapy improves bone mineral density, lean body mass, erectile function, and anemia, there is inconclusive evidence on the benefits of testosterone therapy on cognitive function, energy levels, blood glucose or lipid levels, and controversy remains around whether testosterone therapy affects the risk of cardiovascular events (6-13).”
From Non-testosterone management of male hypogonadism: an examination of the existing literature (2020) · cites this paper as [9]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Though testosterone therapy improves bone mineral density, lean body mass, erectile function, and anemia, there is inconclusive evidence on the benefits of testosterone therapy on cognitive function, energy levels, blood glucose or lipid levels, and controversy remains around whether testosterone therapy affects the risk of cardiovascular events (6-13).”
From Non-testosterone management of male hypogonadism: an examination of the existing literature (2020) · cites this paper as [9]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Though testosterone therapy improves bone mineral density, lean body mass, erectile function, and anemia, there is inconclusive evidence on the benefits of testosterone therapy on cognitive function, energy levels, blood glucose or lipid levels, and controversy remains around whether testosterone therapy affects the risk of cardiovascular events (6-13).”
From Non-testosterone management of male hypogonadism: an examination of the existing literature (2020) · cites this paper as [9]
Experimental — accuracy not yet measuredIn the citing paper
“However, some groups have shown that T replacement in old men does not provide significant benefits in strength 214-217 or cognition,218 increases coronary artery plaque formation,219 and is consistently shown to have no effect on insulin sensitivity.216, 220”
From Hormonal and Metabolic Changes of Aging and the Influence of Lifestyle Modifications (2021) · cites this paper as [218]
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Metadata
- Authors
- Resnick, S. M., Matsumoto, A. M., Stephens-Shields, A. J., Ellenberg, S. S., Gill, T. M., Shumaker, S. A., Pleasants, D. D., Barrett-Connor, E., Bhasin, S., Cauley, J. A., Cella, D., Crandall, J. P., Cunningham, G. R., Ensrud, K. E., Farrar, J. T., Lewis, C. E., Molitch, M. E., Pahor, M., Swerdloff, R. S., Cifelli, D., Anton, S., Basaria, S., Diem, S. J., Wang, C., Hou, X., & Snyder, P. J.
- Affiliations
- National Institutes of Health (US)
- University of Washington (US)
- Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia
- University of Pennsylvania (US)
- Yale University (US)
- Wake Forest University Health Sciences (US)
- University of California San Diego (US)
- Brigham and Women's Hospital (US)
- University of Pittsburgh (US)
- Northwestern University (US)
- Albert Einstein College of Medicine (US)
- University of Minnesota (US)
- University of Alabama at Birmingham (US)
- University of Florida (US)
- University of California, Los Angeles (US)
- Corresponding author
- Snyder, Peter J.
- ORCID
- Resnick, Susan M.
- Matsumoto, Alvin M.
- Ellenberg, Susan S.
- Gill, Thomas M.
- Barrett-Connor, Elizabeth
- Bhasin, Shalender
- Cauley, Jane A.
- Cella, David
- Crandall, Jill P.
- Cunningham, Glenn R.
- Ensrud, Kristine E.
- Farrar, John T.
- Lewis, Cora E.
- Molitch, Mark E.
- Swerdloff, Ronald S.
- Anton, Stephen
- Basaria, Shehzad
- Diem, Susan J.
- Wang, Christina
- Hou, Xiaoling
- Snyder, Peter J.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2017-02-21
- Volume
- 317
- Issue
- 7
- Pages
- 717
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC5433758
- OpenAlex
- W2594566853
- Cited by
- 220
- References
- 36
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 17 · 2023: 18 · 2022: 23 · 2021: 24 · 2020: 27 · 2019: 27 · 2018: 30 · 2017: 25
- FWCI
- 23.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5p60dk079626-05, UL1TR000142, 5p30ag031679-15)
- National Institute on Aging (U01AG030644, R01AG037679, K07AG043587, P30-AG031679, P30AG028740, P30AG021342)
- National Institute of Diabetes and Digestive and Kidney Diseases (P60-DK-079626, P30DK020541, P30DK079626)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- testosterone replacement therapy, androgen deficiency, age-associated memory impairment, cognitive function, verbal memory, older men, testosterone gel, delayed recall, visual memory, executive function, spatial ability, subjective memory complaints, physical function, vitality, hormone replacement therapy
- MeSH terms
- Aged, Androgens, Cognition, Double-Blind Method, Gels, Humans, Male, Memory, Memory Disorders, Mental Recall, Reference Values, Testosterone, Time Factors, Treatment Outcome, Executive Function, Intention to Treat Analysis
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