Androgens

Investigators conducted a substudy of the TRAVERSE trial (Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men; ClinicalTrials.gov Identifier: NCT03518034). Of 5204 men aged 45 to 80 years with hypogonadism, 1175 had prediabetes and 3880 had diabetes. In the prediabetes group, mean hemoglobin A1c level was 5.8% at baseline.

Progression to diabetes did not differ significantly between men receiving testosterone gel vs placebo at 6 months (0.7% vs 1.4%), 12 months (7.8% vs 10.7%), 24 months (10.1% vs 14.6%), 36 months (12.8% vs 15.8%), or 48 months (13.4% vs 15.7%). Further, hemoglobin A1c, glycemic remission, and fasting glucose reduction were comparable, Shalender Bhasin, MB, BS, of Brigham and Women’s Hospital, Harvard Medical School in Boston, Massachusetts, and colleagues reported in JAMA Internal Medicine.

“Testosterone replacement therapy did not improve glycemic control in men with hypogonadism and prediabetes or diabetes,” Dr Bhasin’s team concluded.

Previous research has found that testosterone therapy does not increase the risk for cardiovascular events, fracture, or prostate cancer. It may improve anemia, but not cognitive function. TRT is associated with increased risks of venous thromboembolism, polycythemia, atrial fibrillation, and acute kidney injury.

In an accompanying editorial, Lona Mody, MD, MSc, and Kenneth E. Covinsky, MD, MPh, of University of Michigan, Ann Arbor, commented:

“Thus, the only indication for TRT in men with hypogonadism remains treatment of bothersome symptoms of hypogonadism, generally sexual dysfunction. Further, results of this study suggests that TRT will not benefit glycemic control in men without hypogonadism, despite the inappropriately high rates of use in this group.”

Disclosure: This research was supported by AbbVie, Inc, with additional financial support provided by Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories, LLC. Please see the original reference for a full list of disclosures.

Peter J. Snyder, MD, from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues examined the risk for clinical fracture in a time-to-event analysis subtrial of a randomized placebo-controlled trial that evaluated the cardiovascular safety of testosterone treatment in middle-aged and older men with hypogonadism. Eligible men were aged 45 to 80 years with preexisting, or a high risk for, cardiovascular disease; one or more symptoms of hypogonadism; and 2 morning testosterone concentrations less than 300 ng/dL in fasting plasma samples obtained at least 48 hours apart. A total of 5204 participants were randomly assigned to apply testosterone or placebo gel daily (2601 and 2603, respectively).

The researchers found that a clinical fracture occurred in 3.50 and 2.46% of participants in the testosterone and placebo groups, respectively, after a median follow-up of 3.19 years (hazard ratio, 1.43). For all other fracture end points, the fracture incidence also seemed higher in the testosterone group.

“We did not expect these results, because most previous studies showed that testosterone improved many measures of bone structure and quality,” the authors write.

The study was funded by AbbVie, Acerus Pharmaceuticals, Endo Pharmaceuticals, and Upsher-Smith Laboratories.

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