February 28, 2017

Hormone treatment studied in older men

At a Glance

  • Hormone treatment for one year may improve bone strength and reduce anemia for some older men with a low level of testosterone. But it might also increase cardiovascular risk.
  • Larger studies over a longer period of time are needed to evaluate the possible risks and benefits of testosterone treatment.
Senior men sitting in the park. Researchers reported results from a set of trials on the effects of testosterone treatment in men aged 65 or older. diego_cervo/ iStock/Thinkstock

As men age, the level of the male hormone testosterone usually drops. Some older men have levels far below what is normal for a young adult male. Doctors sometimes prescribe hormone treatment for such men to combat challenges they may have with sexual function, bone fractures, and other symptoms. But large, long-term studies of the benefits and risks of hormone treatment haven’t been conducted.

NIH’s National Institute on Aging (NIA) initiated the Testosterone Trials (TTrials) to find out whether the aging-related symptoms of low testosterone could be treated without significant side effects. In 7 trials at 12 medical centers across the United States, the researchers evaluated hormone treatment for men aged 65 or older who had a low level of testosterone. The trials are supported by NIA and other NIH components.

Participants received either testosterone gel or placebo gel. They were asked to apply it every day for 12 months. The men weren’t told which gel they were given. Regular blood tests assessed hormone levels. For those receiving testosterone gel, the dose was adjusted throughout the study period, if needed, to maintain the hormone level of a young man.

Findings from 3 studies on sexual function, walking, and vitality were reported last year. Results from the other 4 trials—on bone density, anemia, cognition, and cardiovascular risk—appeared in JAMA and JAMA Internal Medicine on February 21, 2017. 

The researchers found an increase in bone density and strength among the men who received hormone treatment. However, a larger study over many years will be needed to determine whether increasing testosterone level can reduce a man’s risk of bone fracture.

Another trial assessed whether hormone treatment affects anemia, a condition in which the blood can’t supply enough oxygen to the body, causing fatigue and other symptoms. Anemia is often caused by low numbers of red blood cells. A greater percentage of men taking testosterone were no longer anemic (58%) after 12 months than those taking placebo (22%).

The researchers did not find a significant effect on memory or cognition from hormone treatment. They did find that treatment increased the build-up of plaque in the artery that supplies blood to the heart. Such build-up is associated with cardiovascular disease. However, the clinical implications are unclear. In another NIH-supported study published in the same issue of JAMA Internal Medicine, men who’d received hormone treatment after a diagnosis of low testosterone were less likely than other men to have had a heart attack, stroke, or other cardiovascular event. This study, however, was also not definitive.

“Clarifying the effects of testosterone on many major clinical outcomes such as cardiovascular events, fractures, and disability will require longer, larger scale trials,” explains Dr. Evan Hadley, director of NIA’s Division of Geriatrics and Clinical Gerontology.

Because the TTrials were conducted in older men with no apparent cause for low testosterone other than aging, these results don’t apply to men with low hormone levels for reasons other than aging. Any man considering hormone treatment should discuss the possible harms and benefits with a health care provider.

Related Links

References: Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone. Budoff MJ, Ellenberg SS, Lewis CE, Mohler ER 3rd, Wenger NK, Bhasin S, Barrett-Connor E, Swerdloff RS, Stephens-Shields A, Cauley JA, Crandall JP, Cunningham GR, Ensrud KE, Gill TM, Matsumoto AM, Molitch ME, Nakanishi R, Nezarat N, Matsumoto S, Hou X, Basaria S, Diem SJ, Wang C, Cifelli D, Snyder PJ. JAMA. 2017 Feb 21;317(7):708-716. doi: 10.1001/jama.2016.21043. PMID: 28241355.

Testosterone Treatment and Cognitive Function in Older Men With Low Testosterone and Age-Associated Memory Impairment. Resnick SM, Matsumoto AM, Stephens-Shields AJ, Ellenberg SS, Gill TM, Shumaker SA, Pleasants DD, Barrett-Connor E, Bhasin S, Cauley JA, Cella D, Crandall JP, Cunningham GR, Ensrud KE, Farrar JT, Lewis CE, Molitch ME, Pahor M, Swerdloff RS, Cifelli D, Anton S, Basaria S, Diem SJ, Wang C, Hou X, Snyder PJ. JAMA. 2017 Feb 21;317(7):717-727. doi: 10.1001/jama.2016.21044. PMID: 28241356.

Effect of Testosterone Treatment on Volumetric Bone Density and Strength in Older Men With Low Testosterone: A Controlled Clinical Trial. Snyder PJ, Kopperdahl DL, Stephens-Shields AJ, Ellenberg SS, Cauley JA, Ensrud KE, Lewis CE, Barrett-Connor E, Schwartz AV, Lee DC, Bhasin S, Cunningham GR, Gill TM, Matsumoto AM, Swerdloff RS, Basaria S, Diem SJ, Wang C, Hou X, Cifelli D, Dougar D, Zeldow B, Bauer DC, Keaveny TM. JAMA Intern Med. 2017 Feb 21. doi: 10.1001/jamainternmed.2016.9539. [Epub ahead of print]. PMID: 28241231.

Association of Testosterone Levels With Anemia in Older Men: A Controlled Clinical Trial. Roy CN, Snyder PJ, Stephens-Shields AJ, Artz AS, Bhasin S, Cohen HJ, Farrar JT, Gill TM, Zeldow B, Cella D, Barrett-Connor E, Cauley JA, Crandall JP, Cunningham GR, Ensrud KE, Lewis CE, Matsumoto AM, Molitch ME, Pahor M, Swerdloff RS, Cifelli D, Hou X, Resnick SM, Walston JD, Anton S, Basaria S, Diem SJ, Wang C, Schrier SL, Ellenberg SS. JAMA Intern Med. 2017 Feb 21. doi: 10.1001/jamainternmed.2016.9540. [Epub ahead of print]. PMID: 28241237.

Association of Testosterone Replacement With Cardiovascular Outcomes Among Men With Androgen Deficiency. Cheetham TC, An J, Jacobsen SJ, Niu F, Sidney S, Quesenberry CP, VanDenEeden SK. JAMA Intern Med. 2017 Feb 21. doi: 10.1001/jamainternmed.2016.9546. [Epub ahead of print]. PMID: 28241244.

Funding: NIH’s National Institute on Aging (NIA), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Neurological Disorders and Stroke (NINDS), and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); and AbbVie Pharmaceuticals.