CHICAGO – , long-awaited results from a major clinical trial show.
Among over 5,000 men aged 45-80 years randomized to daily transdermal testosterone gel or matching placebo gel for an average of 22 months, no increased risk was seen for a first occurrence of any component of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.
There was also no increased risk for prostate cancer over the 33-month follow-up period. However, there were increases in rates of atrial fibrillation, acute kidney injury, and pulmonary embolism in the testosterone group.
In terms of efficacy, testosterone therapy was associated with improved sexual function over two years of treatment and correction, or prevention, of anemia, but had no effect on progression to diabetes or glycemic parameters.
And, an unexpected finding was a significant and unexplained 43% increase in fractures with testosterone therapy.
The TRAVERSE study was mandated by the Food and Drug Administration in 2015 in response to concerns and conflicting data regarding the cardiovascular safety of testosterone replacement therapy in men. It was conducted by a consortium of five manufacturers of testosterone replacement products, led by AbbVie.
The results were presented during a symposium at the annual meeting of the Endocrine Society. The mandated safety data were published online in the New England Journal of Medicine. The efficacy outcomes, undertaken opportunistically due to the trial’s large sample size and relatively long followup time, will be published later this year.
Taken together, the TRAVERSE findings are expected to transform the risk–benefit discussions with patients about the use of testosterone therapy for hypogonadism, study coauthor Shalender Bhasin, MD, told this news organization.
“Testosterone deficiency doesn’t kill people as far as we know but it is really an important symptomatic condition that affects quality of life. Many middle-aged and older men seek assistance for these symptoms, so it’s an important condition and the treatment decisions are complicated,” said Dr. Bhasin, director of the research program in Men’s Health: Aging and Metabolism, at Brigham and Women’s Hospital in Boston.
These new data will be incorporated into future guidelines on testosterone therapy in men with hypoandrogenism, noted Dr. Bhasin, a coauthor of The Endocrine Society’s 2018 guidelines.
Findings apply only to men with bona fide testosterone deficiency
Asked to comment, endocrinologist Bradley D. Anawalt, MD, told this news organization that “the community of physicians who prescribe testosterone to men was waiting with bated breath” for the TRAVERSE results.
Dr. Bradley D. Anawalt
“Until now, we’ve had to say well, there might be a risk of strokes and heart attacks. This study does a lot to say that’s not a serious risk, in the first few years anyway, of testosterone therapy. We still need long-term follow-up in these patients, or others, to see what the long-term risks are, but it’s really reassuring,” added Dr. Anawalt, professor of medicine at the University of Washington, Seattle.
Both Dr. Bhasin and Dr. Anawalt said the TRAVERSE trial in men is similar in many ways to the Women’s Health Initiative (WHI). “[TRAVERSE] is not as big as [WHI], but it’s framed in a similar way to ask those safety questions and to weigh the risk and benefit,” Dr. Anawalt explained.
However, Dr. Anawalt stressed that the TRAVERSE safety data apply only to men with documented testosterone deficiency.
“It’s important to emphasize that this is a study of men with bona fide testosterone deficiency and symptoms. It doesn’t give carte blanche to prescribe to men with normal testosterone concentrations. It doesn’t tell us about the safety of that,” he noted.