Testosterone Offers Modest Gains for Anemia and Bone Density

EndocrineWeb highlights results of the last 2 of 7 studies—looking at the effects of testosterone replacement for anemia and bone strength in older men with low circulating hormone levels—from the National Institutes of Health (NIH) sponsored Testosterone Trials (TTrials).

Interviews with Thomas M. Gill, MD and Tamara L. Wexler, MD, PhD

Given the natural decline in testosterone levels as men age, the potential value of raising testosterone levels, similar to estrogen replacement in women, was ripe for investigation. Highlights from 2 of the last 4 TTrials—looking at the potential for testosterone replacement to lessen cognitive decline and cardiovascular disease—were reported earlier this week.  

These final 2 studies, examining anemia and bone density,  were included in the TTrials because these conditions have been linked to low levels of testosterone in older men, but results from previous research on the efficacy of testosterone treatment were conflicting.

Testosterone supplementation in older men won't lessen the effects of aging, and may worsen chronic diseases in some.

Cindy N. Roy, PhD, program director of the NIH’s division of kidney, urologic, and hematologic diseases, and colleagues examined whether a year of testosterone treatment in older men was able to improve anemia.1

Significantly more men with unexplained anemia showed marked improvements in their hemoglobin level following 1 year of testosterone treatment, according to Dr. Roy, an assistant professor of geriatric medicine and gerontology at Johns Hopkins University School of Medicine in Baltimore, Maryland, and colleagues.

“Testosterone seems to have a general effect of increasing hemoglobin in these men regardless of the baseline levels, and in fact, this is one of the potential adverse consequences of testosterone treatment," Thomas M. Gill, MD, Humana Foundation Professor of Medicine at Yale University School of Medicine in New Haven, CT, told EndocrineWeb.

"It is a blood test that needs to be monitored for men who are treated with testosterone, although benefits were seen in men with known and unknown causes of anemia,” Dr. Gill said.

The Efficacy of Testosterone Replacement for Anemia 

Investigators assessed hemoglobin levels in all participants of the TTrials, and 126 were diagnosed with anemia, defined as hemoglobin levels ≤12.7 g/dL, including 62 patients with no identified cause of anemia. Participants were not informed about or treated for anemia as part of the trial, although a small number took iron supplements outside of the trial.

Dr. Roy reported1 that 54% of the men had improvements in hemoglobin levels of ≥1.0 g/dL than those receiving a placebo (15%) and significantly more men in the treatment group were no longer anemic after 1 year (58.3%) than in the placebo group (22.2%). 

For patients with anemia of known cause, improvements in hemoglobin levels of ≥1.0 g/dL were also significantly associated with testosterone treatment.1 The observed increases in hemoglobin were associated with modest improvements in measures of vitality and physical function.

Among the 336 TTrial participants without anemia, 6 (2%) developed erythrocytosis due to excessive hemoglobin levels of 17.5 g/dL or more, flagging a potential risk of testosterone treatment in men without anemia.1

Research Findings from the Bone TTrial

investigating the efficacy of testosterone treatment for bone health in older men, Peter J. Snyder, MD, professor of medicine at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, PA, and his research team, reported finding significant increases in volumetric bone mineral density (vBMD) and estimated bone strength compared to placebo.2

A total of 211 participants in the TTrials were enrolled in the Bone Trial to assess the possible benefits of short-term testosterone treatment on bone mineral density. Prior to enrollment, none of the participants had signs of osteoporosis nor were they taking any medications known to affect bone heath, except over-the-counter calcium and vitamin D supplements.

The bone investigators assessed vBDM and bone strength of the lumbar spine and hip, at baseline and after 1 year, using quantitative computed tomography, and found significant improvements in both measures, especially in the spine compared to the hip.

“These men didn’t have osteoporosis, and on average, their bones were within the normal range in density and strength,” noted Dr. Gill. “It is unlikely that testosterone would be used solely for the purpose of improving bone health, but if a man were going to be treated with testosterone for another reason; for example, to improve sexual function, he might experience an additional benefit of strengthening his bones.”

TTrial Overview: Results of 7 Testosterone Studies

The results from the previously reported outcomes were published concurrently in the Journal of the American Medical Association  and last year in the New England Journal of Medicine in which short-term testosterone repletion was associated with modest improvements in sexual function, but no improvements in vitality (physical function),3 and significant, adverse increases in noncalcified plaque volume in the coronary arteries,4 while no effect was found in cognitive function.

The findings of testosterone supplementation for anemia and bone health,1,2  were the final 2 outcomes from the TTrial, a set of 7 coordinated trials that set out to examine the short-term effects of testosterone repletion therapy in men aged 65 years or older with low circulating testosterone.

Thomas M. Gill, MD, lead investigator at the Yale study site and coauthor for all the TTrials, told EndocrineWeb that overall, the results from the final 4 TTrials, 

 were mixed, showing a benefit to bone health and anemia, 
no benefit to cognition, and a suggestion of potentially harmful cardiovascular effects.

“[Testosterone treatment] is not the fountain of youth that we might have hoped or expected,” he said. “The best evidence for the benefit of testosterone remains sexual function shown in the results, published in NEJM,3 last year.”

“The most important point to keep in mind is that this is the largest, carefully multi-designed, randomized, clinical trial to look at the effects of testosterone replacement in this cohort,” said Tamara L Wexler MD, PhD, from the NYU Langone Medical Center in New York, New York, in reviewing the studies for EndocrineWeb; she concurred with Dr. Gill that most of the results were unsurprising but important.

“While there may not seem to be exciting media headlines for the takeaways from these results, this study was designed to answer long-standing questions, in a structured way,” said Dr. Wexler, "and this was effectively achieved."

For a full discussion of the testosterone research, view the EndoScan review of the literature.



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