Serum testosterone levels naturally begin to decline gradually with age, but not necessarily to levels below those considered normal for healthy young men. In the NIH-sponsored Testosterone Trials, researchers evaluated the effects of testosterone therapy in 790 men aged 65 years or older with low testosterone and symptoms possibly attributable to low testosterone. In the studies, which were conducted at 12 sites across the country, researchers randomly assigned participants to therapy with testosterone gel or placebo gel, applied daily to the skin. They then measured serum testosterone levels in the participants at 1, 2, 3, 6, 9 and 12 months.
The effects of testosterone gel were evaluated in terms of improvements to sexual function, physical function and vitality, with results published in February 2016. Additional trials, published this year, assessed the effects of testosterone on anemia, bone mineral density, noncalcified coronary artery plaque and cognitive function.
Endocrine Today spoke with study researcher Susan S. Ellenberg, PhD, professor of biostatistics at the University of Pennsylvania’s Perelman School of Medicine, about the design of the T Trials, their recently published findings, and what these findings may mean for clinical practice.
How were the T Trials designed? What were their objectives?
Ellenberg: We designed the trials based on the recommendations of what was then called the Institute of Medicine (IOM) of the National Academies of Science, now the National Academy of Medicine. Those recommendations were motivated by concern about the increased use of testosterone and the limited understanding of the benefits and risks. The IOM recommended that a series of coordinated, randomized studies be done that could determine whether there were any clear advantages to therapy. Then, if benefits were documented, it would be worth doing much larger studies to do a full comparison of the risks and benefits. The primary risk of concern with testosterone treatment has been prostate cancer. In epidemiologic studies, higher levels of testosterone are associated with increased risk for prostate cancer. The concern then is, if you supplement with testosterone, are you going to increase the risk? Of course, our study was too small to assess that — we had only a handful of cases of prostate cancer. More recently, concerns have also arisen regarding cardiovascular risk.
What have been the main findings so far?
Ellenberg: We published the first set of findings about a year ago in The New England Journal of Medicine. That paper reported the results of the three primary studies under the umbrella of the T Trials. Those studies focused on sexual function, vitality and physical function.