Nannan Thirumavalavan, MD, reflects on 1 year of FDA testosterone labeling changes

As we recognize the 1-year anniversary of the FDA’s decision to update labeling for testosterone products, Nannan Thirumavalavan, MD, reflected on how the change has influenced clinical practice and perceptions of testosterone replacement therapy (TRT) over the past year. Thirumavalavan is a urologist at University Hospitals and an associate professor of urology at Case Western Reserve University School of Medicine in Cleveland, Ohio.

Thirumavalavan explained that the FDA’s original cardiovascular warning stemmed from studies published around 2014 and 2015 that suggested testosterone therapy might increase the risk of adverse cardiac events. Those concerns led the agency to require updated labeling and to call for a large-scale outcomes study to more definitively assess safety. That effort resulted in the TRAVERSE trial NCT03518034, which later found no increased risk of major adverse cardiovascular events with TRT compared with placebo in appropriately selected men (HR, 0.96; 95% CI, 0.78 to 1.17; P < .001).¹ Based on those data, the FDA removed the boxed warning in 2025. Thirumavalavan said the change has helped reduce hesitation among both clinicians and patients, contributing to greater interest in treatment over the past year.

He noted that the TRAVERSE findings are particularly relevant because the study enrolled 5246 middle-aged and older men with hypogonadism who also had preexisting cardiovascular disease or elevated cardiovascular risk. Over a mean follow-up of 33 months, major cardiovascular events occurred at similar rates in the testosterone and placebo arms—7.0% and 7.3%, respectively—supporting the cardiovascular safety of TRT when prescribed appropriately and monitored carefully. Thirumavalavan emphasized that these results apply to men treated under physician supervision, with testosterone levels restored from low to normal physiologic ranges.

At the same time, he said the 1-year milestone is also an opportunity to remember that ongoing vigilance remains important. TRAVERSE identified higher rates of pulmonary embolism, atrial fibrillation, and acute kidney injury in the testosterone arm, findings that warrant further study. Although the mechanisms behind these signals remain uncertain, Thirumavalavan said they reinforce the need for individualized patient selection, counseling, and continued monitoring. Overall, he said the past year has brought greater confidence in TRT use, while underscoring the importance of thoughtful, evidence-based prescribing.

REFERENCE

1. Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular safety of testosterone-replacement therapy. N Engl J Med. 2023;389(2):107-117. doi:10.1056/NEJMoa2215025