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 approved, the changes would remove a longtime restriction on age-related low testosterone treatment and revise two major safety warnings.
Since 2015, labeling for testosterone therapy products has included a statement that safety and effectiveness had not been established in men with age-related hypogonadism, a condition of low testosterone without a known underlying cause. HHS is now asking that this limitation be removed.
The restriction was originally added because evidence of benefit was limited and there were concerns about possible cardiovascular risks. After more than a decade of additional research, the FDA has concluded the limitation is no longer needed.
A key factor in 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 therapy. Cardiovascular risk was a primary reason for the 2015 restriction.
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 combined with other randomized controlled trials, this signal was not consistently seen, and no overall increase in cardiovascular risk was found across the broader evidence base.
HHS is also requesting updates to safety information related to prostate health. Under current labeling, testosterone therapy is generally not advised 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 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 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 therapy may worsen BPH symptoms. The FDA review found that available clinical trial data do not show worsening symptoms in men with mild to moderate BPH. 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. It is important to note that this is a request from HHS to the FDA to make these changes. The revisions will be implemented through updated labeling submitted by manufacturers and reviewed through the agency’s standard labeling update process before they appear in clinical use.
For patients navigating a low testosterone diagnosis, these developments may shape how clinicians interpret the benefits and risks of treatment over time.
