The U.S. Department of Health and Human Services announced on June 18 that it is requesting updates to the prescribing information for testosterone replacement therapy. If finalized, the changes would remove a safety statement that has been on labels since 2015 and revise two other major warnings.
Since 2015, labeling for testosterone replacement therapy has included a statement that the safety and effectiveness of the treatment had not been established in men with age-related low testosterone. HHS is now requesting that this limitation be removed.
The original restriction was added because evidence of benefit was limited at the time and concerns had been raised about possible cardiovascular risks. With more than a decade of additional research now available, the FDA has concluded the limitation is no longer warranted.
Central to this decision is the TRAVERSE trial, a large clinical study involving more than 5,200 men. The trial found no meaningful increase in the risk of major adverse cardiovascular events, including heart attack and stroke, among men receiving testosterone replacement therapy.
Cardiovascular risk had been one of the primary reasons the 2015 limitation was put in place. The TRAVERSE trial directly addressed that concern with large-scale clinical evidence.
A 2024 systematic review and meta-analysis identified a potential signal for increased non-fatal arrhythmias, including atrial fibrillation, within the TRAVERSE trial population. However, when data from TRAVERSE were pooled with other randomized controlled trials, this signal was not consistently observed, and no overall increase in cardiovascular risk was detected across the broader evidence base.
HHS is also requesting updates to longstanding safety information related to prostate health. Under current labeling, testosterone replacement therapy is generally inadvisable in men with known or suspected prostate cancer, and the labeling warns that treatment may increase the risk of developing prostate cancer. Under the proposed revisions, testosterone replacement therapy would remain contraindicated only in men with metastatic prostate cancer.
Available clinical trial and epidemiologic data have not generally shown an increased risk of prostate cancer in men receiving testosterone replacement therapy. However, important uncertainties remain because prostate cancer can take years to develop and existing studies may not have followed patients long enough to detect long-term effects. The proposed labeling would continue to recommend that healthcare providers assess risk, screen patients before treatment, and monitor patients during therapy.
Separately, HHS is requesting revisions to warnings related to benign prostatic hyperplasia, also known as enlarged prostate. Current labeling generally warns that testosterone replacement therapy may worsen symptoms. The FDA review found that available clinical trial data do not show worsening symptoms in men with mild to moderate benign prostatic hyperplasia. The proposed changes would revise the warning accordingly, while recommending continued monitoring for men with severe symptomatic disease.
These requested label updates would give physicians and patients a clearer framework for making treatment decisions. This is a request from HHS to make these changes. HHS has asked the FDA to update the prescribing information, and the revisions will be implemented through updated labeling submitted by manufacturers and reviewed through the agency standard labeling update process before they appear in clinical use.
For patients navigating a low testosterone diagnosis, these developments are worth watching, as they may shape how clinicians interpret the benefits and risks of treatment over time.
