TY - JOUR
T1 - Testosterone treatment and cognitive function in older men with low testosterone and age-associated memory impairment
AU - Resnick, Susan M.
AU - Matsumoto, Alvin M.
AU - Stephens-Shields, Alisa J.
AU - Ellenberg, Susan S.
AU - Gill, Thomas M.
AU - Shumaker, Sally A.
AU - Pleasants, Debbie D.
AU - Barrett-Connor, Elizabeth
AU - Bhasin, Shalender
AU - Cauley, Jane A.
AU - Cella, David
AU - Crandall, Jill P.
AU - Cunningham, Glenn R.
AU - Ensrud, Kristine E.
AU - Farrar, John T.
AU - Lewis, Cora E.
AU - Molitch, Mark E.
AU - Pahor, Marco
AU - Swerdloff, Ronald S.
AU - Cifelli, Denise
AU - Anton, Stephen
AU - Basaria, Shehzad
AU - Diem, Susan J.
AU - Wang, Christina
AU - Hou, Xiaoling
AU - Snyder, Peter J.
N1 - Funding Information:
The Testosterone Trials were supported by grant U01 AG030644 from the NIA/NIH, supplemented by funds from the National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; and National Institute of Child Health and Human Development. AbbVie provided funding, AndroGel, and placebo gel. The Boston site was partially supported by grant P30-AG013679 from the Claude D. Pepper Older Americans Independence Center (OAIC). The Yale Field Center was partially supported by grant P30AG021342 from the Claude D. Pepper OAIC and grant UL1TR000142 from the Yale Clinical and Translational Science Award. Additional support was from the Department of Veterans Affairs Puget Sound Health Care System (Dr Matsumoto); the Academic Leadership Award (K07AG043587) from the NIA (Dr Gill); the Intramural Research Program of NIA/NIH (Dr Resnick); grant DK079626 from the National Institute for Diabetes and Digestive and Kidney Diseases of NIH to the University of Alabama at Birmingham Diabetes Research and Training Center (Dr Lewis); grant R01 AG37679 from NIA/NIH (Dr Cauley); and grant 5P30AG031679 from the Boston Claude D. Pepper OAIC (Dr Bhasin).
PY - 2017/2/21
Y1 - 2017/2/21
N2 - 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 outcomewas 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]), 247were 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. Therewas 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 recallwere 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. Testosteronewas 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.
AB - 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 outcomewas 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]), 247were 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. Therewas 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 recallwere 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. Testosteronewas 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.
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U2 - 10.1001/jama.2016.21044
DO - 10.1001/jama.2016.21044
M3 - Article
C2 - 28241356
AN - SCOPUS:85014669084
VL - 317
SP - 717
EP - 727
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
SN - 0002-9955
IS - 7
ER -