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Testosterone Trials Investigate Testosterone’s Effects on Four Outcomes | ISSM

Four studies published recently in JAMA and JAMA Internal Medicine provide new insights on the effects of testosterone therapy on various health outcomes, including memory, bone density, anemia, and coronary artery plaque volume.

The studies were part of the Testosterone Trials (T-Trials), a series of seven linked studies involving men over age 65 who had low testosterone due to aging. (The results of the remaining three T-Trial studies were published last year.)

Overall, 788 men participated in the trials. However, each individual trial included subgroups that pertained to the outcome being studied. Each man had testosterone levels below 275 ng/dL.

Men were divided into two groups. One group used a testosterone gel for one year, with doses adjusted to maintain levels equivalent to those of younger men. The other group was given a placebo gel.

These four trials focused on the following outcomes:

• Memory and Cognitive Function. This trial involved 493 men with age-associated memory impairment. Their average age was 72 years. Two hundred forty-six participants took testosterone; the remaining men used the placebo. The men underwent tests of paragraph recall, visual memory, and spatial ability at baseline and again at six- and twelve-month follow-up points. However, testosterone therapy did not appear to improve memory or cognitive function. “This study does not support the use of testosterone for the treatment of age-associated memory decline in older men with symptomatic hypogonadism,” the authors concluded.

• Coronary Artery Plaque Volume. The trial included 170 participants with an average age of 71 years. (One hundred thirty-eight men completed the trial and were included in the final analysis.) Using coronary computed tomographic angiography, the researchers measured the noncalcified coronary artery plaque volume of each man. After a twelve-month period between baseline and conclusion, the men in the testosterone group had a “significantly greater increase” in coronary artery plaque volume compared to the placebo group. The estimated overall difference was 41 mm3. However, the authors recommended further research to determine clinical significance.

• Anemia. This study involved 126 anemic men with an average age of 75 years. For 62 of the men, the cause of their anemia was unknown. At the end of the 12-month study period, 58.3% of the men in the testosterone group were no longer anemic, compared to 22.2% of men in the placebo group. In addition, testosterone therapy was associated with an increase in hemoglobin levels for men with explained and unexplained anemia. The authors suggested that clinicians check testosterone levels in anemic men over age 65.

• Bone Density and Strength. Two hundred eleven men participated in this study. About half received testosterone; the other half received a placebo. The researchers assessed the men’s bone mineral density at baseline and twelve months using computer tomography, focusing on the spine and hip. Overall, the men in the testosterone group saw greater increases in bone mineral density and strength. Such increases were larger for the spine when compared to the hip and for the trabecular bone compared to the peripheral bone. The authors noted that a longer trial with more participants could help determine whether testosterone therapy might reduce the risk of fracture.



Matthew J. Budoff, MD, et al. “Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone” (Abstract. February 21, 2017)

Resnick, Susan M., PhD, et al. “Testosterone Treatment and Cognitive Function in Older Men With Low Testosterone and Age-Associated Memory Impairment” (Abstract. February 21, 2017)

JAMA Internal Medicine

Roy, PhD, Cindy N., et al. “Association of Testosterone Levels With Anemia in Older Men” (Abstract. April 2017)

Snyder, Peter J., MD, et al. “Effect of Testosterone Treatment on Volumetric Bone Density and Strength in Older Men With Low Testosterone” (Abstract. April 2017)

The JAMA Network

“Five Studies in JAMA, JAMA Internal Medicine Examine Effect of Testosterone Treatment on Various Health Outcomes” (News release. February 21, 2017)


McCall, Becky “Bone Density, Anemia Improve With Testosterone in Low-T Men” (February 23, 2017)

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