Effects of long-term testosterone administration on cognition in older men with low or low-to-normal testosterone concentrations: a pre-specified secondary analysis of data from the randomized, double-blind, placebo-controlled TEAAM trial

Anna Gawrys, Mercer University College of Pharmacy


As men age, testosterone level decreases due to lower testicular production and increase in sex hormone binding globulin. [2]


Endocrine Society clinical practice guidelines recommend testosterone replacement therapy (TRT) for men with symptomatic androgen deficiency. [1]


It is suggested that TRT beneficial effects include increasing bone strength and density, inducing hematopoiesis, driving sexual function and libido, providing a cardioprotective effect, and increasing muscle strength. [3]


The therapy is said to be associated with the risk of exacerbation of prostate cancer, male breast cancer, worsening benign prostatic hyperplasia, liver toxicity, gynecomastia, polycythemia and an increased risk of obstructive sleep apnea. [4]


Title: Effects of Long-Term Testosterone Administration on Cognition in Older Men with Low or Low-to-Normal Testosterone Concentrations: A Prespecified Secondary Analysis of Data From the Randomized, Double-Blind, Placebo-Controlled TEAAM Trial [5]

Design Randomized, double-blind, placebo-controlled, parallel-group trial; N= 308
Objective To establish the effects of long-term testosterone administration on multiple domains of cognitive function in older men with low or low-to-normal testosterone concentrations
Study Groups Testosterone gel (n= 156 ); placebo (n= 152)
Methods Men aged 60 years and older with low or low-to-normal testosterone were randomly assigned (1:1) to receive either 7.5 g of 1% testosterone gel or placebo gel daily for three years. Multiple domains of cognitive function were assessed at baseline and months 6, 18, and 36.
Duration Sept 1, 2004 – Feb 12, 2009
Primary Outcome Measure Multiple domains of cognitive function
Baseline Characteristics Testosterone group (n= 140) Placebo group (n= 140)
Age, y 66.9 68.2
White, n (%) 112 (80) 111 (79)
Higher education (at least college level), n (%) 75 (56%) 87 (66)
Total testosterone (nmol/L) 10.6 10.7
Sex hormone-binding globulin (nmol/L) 33.0 33.4
Results Estimate, 95% Confidence Interval (difference between testosterone and placebo)* P-value
Visuospatial Ability Complex Figure Test, immediate (n) -0.51 (-2.03, 1.01) 0.512
Phonemic or Category Verbal Fluency Phonemic Fluency Test, total (n) 0.90 (-1.33, 3.12) 0.428
Categorical Fluency Test, (n) 1.13 (-0.33, 2.59) 0.129
Verbal Memory Paragraph Recall Test, delayed (n) 0.29 (-1.21, 1.79) 0.705
Manual Dexterity Grooved Pegboard Test, seconds (n) 4.23 (-1.27, 9.73) 0.131
Attention or Executive Function Stroop Interference Test, n -2.55 (-7.37, 2.27) 0.299
* The comparison was between data collected at baseline and then at 36 months.
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: N/A
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions Testosterone administration for 36 months in older men with low or low-to-normal testosterone concentrations did not improve cognitive function. Future long-term trials are needed to investigate the efficacy of testosterone replacement in patients with impaired cognition, such as people with Alzheimer’s disease.



As lifespans continue to increase, researchers are looking for ways to improve cognition and prevent dementia. While current pharmacological options to treat dementia are limited, testosterone treatments have many positive effects on increasing bone mass and strengthening the heart muscle. However, testosterone therapy does not offer help in deteriorating mental status of older men per this study. The limitation of this study is its small number of participants and predominantly white population. This trial will not impact prescribing practices of testosterone for other purposes than its pure androgenic function in the body.




  1. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536-59.
  2. Basaria S, Dobs AS. Risks versus benefits of testosterone therapy in elderly men. Drugs Aging.1999;15:131–42.
  3. Gruenewald DA, Matsumoto AM. Testosterone supplementation therapy for older men: Potential benefits and risks. J Am Geriatr Soc. 2003;51:101–15.
  4. Bassil N, Alkaade S, Morley JE. The benefits and risks of testosterone replacement therapy: a review. Ther Clin Risk Manag. 2009;5(3):427-48.
  5. Huang G, Wharton W, Bhasin S, et al. Effects of long-term testosterone administration on cognition in older men with low or low-to-normal testosterone concentrations: a prespecified secondary analysis of data from the randomised, double-blind, placebo-controlled TEAAM trial. Lancet Diabetes Endocrinol. 2016.

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