What men should know about proposed changes for testosterone therapy
Treatment might become more easily accessible, but it isn't right for everyone.
- Reviewed by Marc B. Garnick, MD, Editor in Chief, Harvard Medical School Annual Report on Prostate Diseases; Editorial Advisory Board Member, Harvard Health Publishing
Millions of men already take testosterone replacement therapy (TRT) to treat symptoms such as chronic fatigue and reduced libido. Now the FDA is calling for significant changes to TRT labeling. And those changes could substantially broaden TRT’s accessibility.
A key hormone
Produced mainly in the testicles, testosterone is a hormone with vital roles in men’s health. It builds and preserves muscle mass, supports libido and mental resilience, and helps maintain energy and an overall sense of well-being. It also declines steadily with age, with levels falling by about 1% to 2% per year after men reach age 30.
If a man’s testosterone level drops below normal levels and he has symptoms like fatigue or erectile dysfunction, he may be diagnosed with age-related hypogonadism. TRT, which is formulated in gels, skin patches, and injectables, might ease symptoms — but not without controversial risks.
In 2014, the FDA warned of reports linking TRT with a higher risk of stroke, heart attack, and death, and urged extra caution when prescribing the hormone for men with prostate cancer or an enlarged prostate. But the thinking is shifting.
A sweeping regulatory shift
The FDA’s proposed labeling changes for TRT were prompted by results from the TRAVERSE clinical trial. The industry-sponsored study found no elevated risk of cardiovascular events (such as stroke or heart attack) or prostate diseases in men taking TRT for age-related hypogonadism. However, compared with men who were given a placebo, the TRT-treated men in the study had higher risks for other side effects, including atrial fibrillation, acute kidney injury, and blood clots in the lungs.
Based on the study results, the FDA recommended last year that manufacturers remove cautionary language from TRT labels warning of a higher risk of heart attack and stroke. At that time, the agency also proposed that certain testosterone products include a new warning about potential treatment-related increases in blood pressure.
This year, the FDA has proposed additional changes. The agency is requesting that product labels drop language stating that TRT’s safety and effectiveness are unproven in men with age‑related hypogonadism.
The FDA will continue specifying that men with metastatic prostate cancer should not use testosterone. For men with low-grade localized known or suspected prostate cancer, the FDA suggests a less strict warning. While testosterone may stimulate growth of some existing prostate cancer, these men can discuss the pros and cons of appropriate TRT with their physician.
Finally, the FDA is recommending that companies update TRT warnings for prostate enlargement (BPH), citing evidence that men with mild to moderate symptoms can still consider TRT. Men with severe symptoms should avoid it.
Important insight
For insights into the FDA’s proposed changes on TRT and their potential implications for men’s health, we turned to Dr. Marc B. Garnick, Gorman Brothers Professor of Medicine at Harvard Medical School and the Beth Israel Deaconess Medical Center, and Editor in Chief of the Harvard Special Health Report Guide to Prostate Diseases.
Q: What is the FDA trying to communicate with this new stance on TRT?
Dr. Garnick: I think they’re clearly easing the ability of men to access TRT and also easing the hesitancy of prescribers to make it available.
Q: Who should get TRT, in your opinion?
Dr. Garnick: These therapies were first approved for patients who had little to no testosterone, such as people with Klinefelter’s disease [a genetic condition that prevents the testicles from making enough of the hormone], for instance, or someone who had both of their testicles removed. In such cases, TRT is definitely medically appropriate. But the FDA based its approval of these medicines on normalizing blood testosterone levels, and not on measures of effectiveness at relieving symptoms.
Q: What about men with age-related hypogonadism?
Dr. Garnick: This condition is defined as two separate morning testosterone values of less than 300 nanograms per deciliter, when blood levels of the hormone are typically at their peak, along with symptoms such as decreased libido, fewer spontaneous erections, fatigue, less energy, or depressed mood. These symptoms vary from man to man, and can also result from other factors, like insufficient sleep. I suspect that that the number of men whose symptoms improve dramatically with TRT will be fewer than expected. That said, if men with symptoms of hypogonadism are aware of the risks and have an informed discussion with their physician, I think it’s perfectly appropriate to give TRT a try.
Q: What underlying health conditions should make a man especially cautious about starting TRT?
Dr. Garnick: The TRAVERSE study did show some worrying findings, specifically atrial fibrillation, acute kidney injury, and pulmonary blood clots. Many of the men who developed these problems may have had pre-existing abnormalities in platelet function or in coagulation factors that predispose them to blood clots. If I’m counseling a man who is contemplating TRT, I make sure he doesn’t have underlying clotting issues. Testosterone therapy can increase red blood cell counts, measured as hemoglobin and hematocrit. These lab values need to be monitored regularly to avoid high levels that may give rise to circulatory problems.
Q: Testosterone fuels the growth of prostate tumors and many treatments for the disease suppress the hormone. How should men considering TRT think about prostate cancer?
Dr. Garnick: Clearly men with metastatic prostate cancer should not get TRT. The real issue for me concerns men who have had localized prostate cancer and are now five or more years out from therapy without any evidence of recurrence. There are some data to suggest that you can give those patients TRT safely, but those results aren’t from randomized clinical trials.
Q: Should those men be closely monitored?
Dr. Garnick: Absolutely! Everybody on TRT should be monitored with routine prostate specific antigen (PSA) checks, in addition to red blood cell count checks. I’ve had patients referred in my own practice who were diagnosed with prostate cancer when their PSA started rising after having received TRT. Testosterone administration can cause small elevations in PSA levels, which then led to a diagnosis of prostate cancer that was most likely pre-existing.
Is TRT safe if you have an enlarged prostate?The prostate continues to grow with age, and the degree of growth varies widely between men. Benign prostate hyperplasia (BPH) occurs when an enlarged prostate impedes the flow of urine out of the bladder. BPH can significantly impair quality of life, eventually progressing to urinary retention, catheter dependence, or surgery. But what if you also have low testosterone? Can you take testosterone replacement therapy? “Prostate growth is testosterone-dependent. Although the TRAVERSE clinical trial did not demonstrate worsening urinary symptoms in men with mild or moderate symptoms, these carefully selected men were followed for less than three years. It remains uncertain how younger men will fare over potentially decades of testosterone treatment as their prostates continue to age and grow,” says Dr. Heidi Rayala, an assistant professor of surgery at Harvard Medical School and a urologic surgeon at Beth Israel Deaconess Medical Center. Counseling, Dr. Rayala notes, “should consider a man’s age, severity of prostate-related symptoms, family history of prostate cancer, likely duration of testosterone therapy, and especially goals for sexual function. This is particularly important because treatments for BPH may themselves negatively affect sexual function.” |
Image: © FatCamera/Getty Images
About the Author
C.W. Schmidt, Editor, Harvard Medical School Annual Report on Prostate Diseases
About the Reviewer
Marc B. Garnick, MD, Editor in Chief, Harvard Medical School Annual Report on Prostate Diseases; Editorial Advisory Board Member, Harvard Health Publishing
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