HHS Just Changed Its Stance On Testosterone Therapy—What It Means For You
Most men assume that if their testosterone is low, they can get treatment. But since 2015, FDA labeling has included cautionary language noting that the safety and effectiveness of testosterone therapy in age-related low testosterone had not been established.
But on June 18, the U.S. Department of Health and Human Services (HHS) announced that it is requesting updates to testosterone replacement therapy (TRT) prescribing information (labeling). If finalized, the changes would remove that statement and revise two other major safety warnings.
The HHS wants to remove this age-related limitation
Since 2015, testosterone replacement therapy product labeling has included a limitation stating that safety and effectiveness had not been established in men with age-related hypogonadism, a condition involving low testosterone levels without a known underlying cause. 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.
The trial that showed no meaningful cardiovascular risk
Central to this decision is the TRAVERSE trial,1 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, so this was a significant finding. The TRAVERSE trial directly addressed that concern with large-scale clinical evidence.
It’s worth noting that a 2024 systematic review and meta-analysis2 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.
The HHS asks to revise labeling about prostate health
HHS is also requesting updates to longstanding safety information related to prostate health.
Under current labeling, TRT 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, TRT 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 TRT. 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. This is why 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 (BPH), also known as enlarged prostate. Current labeling generally warns that TRT may worsen BPH symptoms. The FDA's 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.
The takeaway
These requested label updates would give physicians and patients a clearer, more current framework for making treatment decisions. But it's important to note that this is simply 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’s 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.