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Testosterone Treatment, A Risky Bet?

Testosterone Treatment, A Risky Bet?

Age-related memory decline in men is often accompanied by a decrease in testosterone levels. But can restoring testosterone levels improve memory?

New findings published in the Journal of the American Medical Association (JAMA) suggest the answer is no [1]. Testosterone treatment did not improve cognitive function in older men with low testosterone, but alarmingly, it was associated with a significantly greater increase in coronary artery plaques [2].

These findings come from the Testosterone Trials (TTrials), a set of seven clinical trials conducted across the United States that tested whether testosterone improves different aspects of aging, such as anemia, bone health, cardiovascular health, cognition, physical function, and sexual function. The cognition arm of the trial included 493 men aged 65 years or older with age-related memory impairment and low levels of testosterone [1]. Results showed that men who received testosterone treatment for one year did not experience improvement in verbal memory, visual memory, executive function, or spatial ability when compared to men who received the placebo. These findings were similar to those from a previous clinical trial that tested the treatment over three years in healthy older men with low testosterone levels [3].

The results from the cardiovascular arm of the TTrials were more concerning. Men receiving testosterone treatment for a year had a greater increase in coronary artery plaque volume compared to those receiving placebo [2]. The type of plaque that increased—noncalcified plaque—is associated with reduced blood flow to the heart and subsequent cardiovascular problems. Although no one experienced heart attacks or other major adverse cardiovascular events during the treatment period, the trial was too short to determine whether testosterone treatment increases risk of cardiovascular disease.

Currently, testosterone treatment is only approved as replacement therapy for men with hypogonadism, a medical condition in which the gonads produce little or no hormones [4]. In September 2014, the FDA mandated that manufacturers of testosterone treatments perform long-term safety and efficacy trials for off-label use [5], and revise labeling to clarify that efficacy and safety have not been established for people with age-related low testosterone.

If your low testosterone levels are not caused by hypogonadism, but are instead related to normal aging or other conditions such as obesity and type 2 diabetes, it is most safely managed by lifestyle changes including a healthy diet and exercise.

  1. Resnick SM, Matsumoto AM, Stephens-Shields AJ et al. (2017) Testosterone Treatment and Cognitive Function in Older Men With Low Testosterone and Age-Associated Memory Impairment. JAMA 317, 717-727.
  2. Budoff MJ, Ellenberg SS, Lewis CE et al. (2017) Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone. JAMA 317, 708-716.
  3. Vaughan C, Goldstein FC, Tenover JL (2007) Exogenous testosterone alone or with finasteride does not improve measurements of cognition in healthy older men with low serum testosterone. J Androl 28, 875-882.
  4. Handelsman DJ (2017) Testosterone and Male Aging: Faltering Hope for Rejuvenation. JAMA 317, 699-701.
  5. (2014) Summary Minutes of the Bone, Reproductive and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee Meeting September 17, 2014 (PDF). Food and Drug Administration Center for Drug Evaluation and Research.

Yuko Hara, PhD, is Director of Aging and Alzheimer's Prevention at the Alzheimer's Drug Discovery Foundation. Dr. Hara was previously an Assistant Professor in Neuroscience at the Icahn School of Medicine at Mount Sinai, where she remains an adjunct faculty member. Her research focused on brain aging, specifically how estrogens and reproductive aging influence the aging brain's synapses and mitochondria. She earned a doctorate in neurology and neuroscience at Weill Graduate School of Medical Sciences of Cornell University and a bachelor's degree in biology from Cornell University, with additional study at Keio University in Japan. Dr. Hara has authored numerous peer-reviewed publications, including articles in PNAS and Journal of Neuroscience.

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