Re: Docket No. FDA-2025-N-6743 for “Food and Drug Administration Expert Panel on Testosterone Replacement Therapy for Men; Request for Information.”
The National Center for Health Research (NCHR) appreciates the opportunity to share our analysis of the risks and benefits of “testosterone replacement therapy” (TRT) for men as they age. NCHR is a nonprofit research center that focuses on the safety and effectiveness of medical and consumer products. We do not accept funding from entities that have a financial interest in our analyses, so we have no conflicts of interest.
There is one well-designed study on testosterone treatment for men that provides key information. Due to concerns about testosterone harming cardiovascular health, TRAVERSE, a major 2-year randomized controlled trial, tested transdermal testosterone that was calibrated to bring participants’ low testosterone levels to normal levels. The results found it increased blood pressure, atrial fibrillation, and other nonfatal heart arrhythmia, but did not increase cardiovascular events. The TRAVERSE data also indicated that testosterone increased kidney injury. These findings raise serious because it was only a 2-year study and focused on normal testosterone levels. These findings could potentially underestimate the likely impact on how testosterone is used in practice.
Although the 2-year trial was too short to detect any increased prostate cancer risk, TRAVERSE found that testosterone increased PSA levels, which can predict risk of prostate cancer many years in advance. Whether men taking testosterone are more likely to develop prostate cancer requires longer-term research.
There have been claims that testosterone helps bone health. Although studies have shown that testosterone increases bone density, TRAVERSE results indicated a significant increase in fractures. This is consistent with studies showing drugs that increase bone density in women can also result in fractures.
The FDA’s December 2025 expert panel on testosterone was enthusiastic about testosterone, but the meeting was focused on opinions, not solid scientific evidence. Discussion of data did not adequately mention risks and provided some misleading information about benefits. Personal experiences can be useful in understanding data when there are clear, consistent patterns, but should not replace scientific evidence.
Testosterone is not a fountain of youth or vitality. Clinical trials indicate it does not reduce or prevent chronic fatigue, irritability, weight gain, or depression. Although there is some evidence that it increases libido, studies have reported that it does not improve sexual function or treat erectile dysfunction. In the doses given for low testosterone, it does not improve strength or physical ability. Moreover, there is no established relationship between “Low-T” and most of the symptoms that testosterone is being promoted to treat.
There is considerable interest and demand for testosterone to treat the normal signs and symptoms of aging, but no solid scientific evidence that it is effective for that use. It is possible that the risks and benefits of TRT might differ based on timing, age of the patient, duration of use, formulation, or dose, but well-designed randomized controlled clinical trials would be needed to determine any such benefits or risks. Meanwhile, since the risks of testosterone treatment include blood clots, testicular atrophy, sleep apnea, worsening congestive heart failure, and polycythemia, it is therefore clear that the risks outweigh the few established benefits.
The pressure on the FDA to give its seal of approval to testosterone for men is similar to presentations made about testosterone for women at the FDA’s July expert panel meeting on hormones for menopause. We note that a recent systematic review of randomized controlled trials found that it had a very small increase (less than one per month) in women’s sexual events, and did not establish any benefit for women’s cognitive function or musculoskeletal health. Similarly, observational studies did not establish a significant link between women’s testosterone levels and cardiovascular or musculoskeletal health, mood, depression, or cognitive function. Unfortunately, there are no long-term data on the risks of testosterone for women, although post-menopausal women with high levels of endogenous testosterone have a higher risk for breast cancer,
Based on HHS’ goal of relying on gold-standard science, the FDA should not propose changes in indication or labeling of testosterone for men or women at this time. Well-designed randomized controlled clinical trials of sufficient size and duration are needed before any changes should be instituted.
Respectfully submitted,
National Center for Health Research