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NIH-supported trials of testosterone therapy in older men report mixed results

Hormone treatment improved bone strength and hemoglobin levels; may increase cardiovascular risk; had no effect on cognition



February 21, 2017

Barbara Cire | 301-496-1752 | nianews3@mail.nih.gov



In older men with low testosterone, one year of testosterone treatment improved bone density and corrected anemia of both known and unknown causes, but also increased the volume of coronary artery plaque, according to results reported from the Testosterone Trials (T Trials). Testosterone treatment had no effect on memory or other cognitive function. The results are reported in two journals coming out this week.

The T Trials were conducted at 12 sites across the country in 790 men age 65 and older with low levels of testosterone and symptoms to which low testosterone might contribute. The studies were funded primarily by the National Institute on Aging (NIA), part of the National Institutes of Health (NIH). Additional funding came from the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, all part of NIH. Additional funding, and the study drug and placebo, were provided by AbbVie Pharmaceuticals.

“A number of older men have testosterone levels below those found in healthy younger men, said NIA Director Richard J. Hodes, M.D. “In most cases, these low levels are not due to diseases known to affect testosterone levels. Many of these men also have problems that could be related to low testosterone, including impaired cognition, anemia, cardiovascular disease, diminished sexual function, decreased mobility, and fatigue. The T Trials were designed to determine if testosterone treatment might help alleviate these symptoms and conditions while monitoring for adverse effects.”

The findings were reported in journals of the American Medical Association cited below, by principal investigator Peter J. Snyder, M.D., professor of medicine in the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and colleagues at the 12 study sites.

Participants were randomly assigned to receive testosterone gel or a placebo gel applied to the skin daily. Serum testosterone concentration was measured at 1, 2, 3, 6, 9, and 12 months. The men were also closely monitored for prostate and cardiovascular problems. In addition to low testosterone, the presence of complaints such as low sexual function, difficulty in walking, or low vitality was required for eligibility to participate in the trials. The results of these outcomes were reported in 2016.

The study also measured testosterone treatment’s effects on additional outcomes in the study population, which are reported in the current publications. Effects on anemia and bone density appear on Feb. 21 in JAMA Internal Medicine. The results of the cardiovascular and cognitive function trials will also appear on Feb. 21 in the Journal of the American Medical Association.

JAMA Internal Medicine

  • Anemia trial – Of all the men enrolled in the T Trial, 64 had anemia from known causes, and 62 had unexplained anemia. After one year of treatment, 54 percent of the men with unexplained anemia and 52 percent of those with anemia from known causes had clinically significant increases in hemoglobin (red blood cell) levels, compared with 15 percent and 12 percent, respectively, of those in the placebo group. These changes may be of clinical significance, as suggested by the magnitude of the changes, the correction of anemia in the majority of men, and the association of the increases with improvements in global impression of change in overall health and energy. Measurement of testosterone might be considered in men age 65 and older who have unexplained anemia and symptoms suggestive of low testosterone levels.
  • Bone trial – The goal of this trial was to determine whether testosterone treatment would increase volumetric bone mineral density (vBMD)—the amount of mineral in bone—and estimated bone strength in older men with low testosterone. vBMD, a marker of increased risk for fractures, was measured in hip and spine at baseline and 12 months later. After one year of treatment, older men with low T significantly increased vBMD and estimated bone strength compared to controls, more so in the spine than in the hip. A larger and longer trial would be needed to determine if testosterone treatment reduces fracture risk.

Journal of the American Medical Association

  • Cardiovascular trial – The study assessed the effects of testosterone treatment on the progression of noncalcified coronary artery plaque—a buildup within the walls of the blood vessels in the heart—which is a risk factor for cardiovascular disease. The study found that noncalcified plaque volume increased significantly more in the testosterone-treated group compared to controls, as measured by coronary computerized tomographic arteriography, a special type of heart scan. The researchers note that, because just 170 men had the scans, the clinical importance is uncertain and may depend on how testosterone affects different components of plaque. A larger and longer trial is needed to establish the clinical significance of these findings.
  • Cognition trial – This trial sought to determine if testosterone treatment improved cognition in older men with age-associated memory impairment (AAMI), a mild form of impairment, distinct from dementia. Of the initial participants in the T Trials, 493 met the criteria for AAMI. After one year of treatment, there were no significant differences between the testosterone treatment and the placebo groups.

“The results on diverse outcomes indicate the potential trade-offs between benefits and risks of testosterone treatment in older men,” said Evan Hadley, M.D., director of NIA’s Division of Geriatrics and Clinical Gerontology. “However, clarifying the effects of testosterone on many major clinical outcomes such as cardiovascular events, fractures, and disability will require longer, larger-scale trials. The results also illustrate that decisions about testosterone treatment need to be individualized, taking into account each patient’s balance of risks for the various conditions that testosterone treatment could affect.”

More information about the Testosterone Trial is available at https://clinicaltrials.gov/ct2/show/NCT00799617?term=NCT00799617&rank=1.

The U.S. Food and Drug Administration has additional information about testosterone.

About the National Institute on Aging (NIA): The NIA leads the federal government effort conducting and supporting research on aging and the health and well-being of older people. The Institute’s broad scientific program seeks to understand the nature of aging and to extend the healthy, active years of life. For more information on research, aging, and health, go to www.nia.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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