madman
Super Moderator
Testosterone Therapy for the Treatment of Age-Related Hypogonadism: Risks with Uncertain Benefits (2021)
Christine P. Nguyen, Mark Hirsch, Suresh Kaul, Corinne Woods, and Hylton V. Joffe
Abstract Testosterone replacement therapy has been approved in the United States since the 1950s for men with ‘‘classical’’ hypogonadism. These men have specific and well-recognized hypothalamic, pituitary, or testicular conditions leading to deficient or absent endogenous testosterone. A more controversial treatment population is aging men, many with comorbidities, who have low serum testosterone concentrations compared with young healthy men and who do not have the well-recognized medical conditions that cause ‘‘classical’’ hypogonadism. Testosterone continues to be widely used in these men with ‘‘age-related hypogonadism’’ even though the benefits of testosterone for this use are uncertain and there are important risks, including a potential risk of major adverse cardiac events for the testosterone class, and two testosterone products with increases in blood pressure that can increase the risk of myocardial infarction and stroke. Given the uncertain clinical benefit of testosterone in men with ‘‘age-related hypogonadism’’ in the face of known and potential adverse outcomes, none of the testosterone products is FDA approved for such use.
*In summary, although they're still appears to be considerable use of testosterone for ‘‘age-related hypogonadism,’’ the labeling for testosterone therapies either states that the effectiveness and safety of such use have not been established or that such use is contraindicated. We recognize that recommendations and guidelines from professional societies on testosterone use for clinical conditions consistent with ‘‘age-related hypogonadism’’ do not necessarily align with the FDAapproved use of testosterone. The FDA approves a drug, including testosterone, for its intended use only when data submitted to FDA show benefits for such use demonstrated with substantial evidence from adequate and well-controlled trials and those benefits outweigh the known and potential risks. Once the FDA approves a drug, a health care provider may prescribe the drug for an unapproved use when the health care provider judges that it is medically appropriate for the patient. FDA does not regulate this off-label use, which is considered the practice of medicine. However, because most of the testosterone use is in patients with ‘‘age-related hypogonadism,’’ it is important for the public to know that the FDA is not aware of substantial evidence from adequate and well-controlled trials that establish benefits of testosterone in these men in the face of significant known and potential safety concerns with these drugs.
Understanding the Controversy Regarding Treatment of Age-Related Testosterone Deficiency (2021)
Abraham Morgentaler
In this volume of Androgens: Clinical Research and Therapeutics (the Journal), we present the Journal’s first point-counterpoint on one of the key issues in the field, namely whether testosterone (T) therapy (TTh) should be offered to men with what has been called ‘‘age-related hypogonadism.’’1,{ Writing in favor of treatment for men with age-related testosterone deficiency (TD) is Abdulmaged Traish, MBA, Ph.D., Editor-in-Chief of the Journal, 2 and arguing against the treatment of these men is Christine Nguyen, MD, and colleagues from the Food and Drug Administration (FDA) in the United States.3
The Journal is delighted to have such prominent authors express their views, and, in particular, we appreciate Dr. Nguyen and colleagues from the FDA engaging in this timely and much-needed scientific debate to explain their position to the public. Indeed, this debate largely exists because of the FDA, which appears to have coined the phrase ‘‘age-related hypogonadism’’ in a 2015 publication in which several of the same authors argued that TTh use should be restricted to men with specific long-known causes of TD and should not be offered to men without those specific conditions. Nguyen and colleagues suggested that low T levels occurred in men without these known conditions ‘‘for no discernable reason other than older age.’’1
The controversy arises because professional society guidelines from prominent medical groups such as the Endocrine Society4 and the American Urological Association,5 as well as clinical recommendations from other groups,6,7 make no such distinction based on etiology of TD, and recommend treatment for those with characteristic symptoms and/or signs of TD confirmed by low serum T levels.
As Dr. Traish ably explains,2 the biological effects and symptoms of TD occur from reduced levels of T, regardless of underlying etiology. So, it has been perplexing to clinicians and researchers alike why the FDA would take the position that a man with a pituitary tumor and a low serum T level would merit treatment, but a man without a pituitary tumor would not merit treatment, even with identical symptoms and serum T levels.
*The FDA is a critically important government institution charged with the protection of our public health. Yet it must be emphasized that its role is to regulate the pharmaceutical industry, and not health care providers. It bears emphasis that the FDA is not involved with the practice of medicine. Yet the medical community and insurance companies pay close attention to the FDA’s positions and insurance companies frequently restrict coverage based on FDA labels, especially if it helps their bottom line.
Although pressures on a regulatory agency such as the FDA differ substantially from those of health care providers and medical groups, it is to be hoped that the entirety of the scientific community, including the FDA, will soon come to recognize the importance of TTh not only for its symptomatic benefits in men with age-related TD but also for its impact on general health. I encourage everyone interested in TD and its treatment to read the excellent articles by Traish2 and by Nguyen and colleagues.3*
Christine P. Nguyen, Mark Hirsch, Suresh Kaul, Corinne Woods, and Hylton V. Joffe
Abstract Testosterone replacement therapy has been approved in the United States since the 1950s for men with ‘‘classical’’ hypogonadism. These men have specific and well-recognized hypothalamic, pituitary, or testicular conditions leading to deficient or absent endogenous testosterone. A more controversial treatment population is aging men, many with comorbidities, who have low serum testosterone concentrations compared with young healthy men and who do not have the well-recognized medical conditions that cause ‘‘classical’’ hypogonadism. Testosterone continues to be widely used in these men with ‘‘age-related hypogonadism’’ even though the benefits of testosterone for this use are uncertain and there are important risks, including a potential risk of major adverse cardiac events for the testosterone class, and two testosterone products with increases in blood pressure that can increase the risk of myocardial infarction and stroke. Given the uncertain clinical benefit of testosterone in men with ‘‘age-related hypogonadism’’ in the face of known and potential adverse outcomes, none of the testosterone products is FDA approved for such use.
*In summary, although they're still appears to be considerable use of testosterone for ‘‘age-related hypogonadism,’’ the labeling for testosterone therapies either states that the effectiveness and safety of such use have not been established or that such use is contraindicated. We recognize that recommendations and guidelines from professional societies on testosterone use for clinical conditions consistent with ‘‘age-related hypogonadism’’ do not necessarily align with the FDAapproved use of testosterone. The FDA approves a drug, including testosterone, for its intended use only when data submitted to FDA show benefits for such use demonstrated with substantial evidence from adequate and well-controlled trials and those benefits outweigh the known and potential risks. Once the FDA approves a drug, a health care provider may prescribe the drug for an unapproved use when the health care provider judges that it is medically appropriate for the patient. FDA does not regulate this off-label use, which is considered the practice of medicine. However, because most of the testosterone use is in patients with ‘‘age-related hypogonadism,’’ it is important for the public to know that the FDA is not aware of substantial evidence from adequate and well-controlled trials that establish benefits of testosterone in these men in the face of significant known and potential safety concerns with these drugs.
Understanding the Controversy Regarding Treatment of Age-Related Testosterone Deficiency (2021)
Abraham Morgentaler
In this volume of Androgens: Clinical Research and Therapeutics (the Journal), we present the Journal’s first point-counterpoint on one of the key issues in the field, namely whether testosterone (T) therapy (TTh) should be offered to men with what has been called ‘‘age-related hypogonadism.’’1,{ Writing in favor of treatment for men with age-related testosterone deficiency (TD) is Abdulmaged Traish, MBA, Ph.D., Editor-in-Chief of the Journal, 2 and arguing against the treatment of these men is Christine Nguyen, MD, and colleagues from the Food and Drug Administration (FDA) in the United States.3
The Journal is delighted to have such prominent authors express their views, and, in particular, we appreciate Dr. Nguyen and colleagues from the FDA engaging in this timely and much-needed scientific debate to explain their position to the public. Indeed, this debate largely exists because of the FDA, which appears to have coined the phrase ‘‘age-related hypogonadism’’ in a 2015 publication in which several of the same authors argued that TTh use should be restricted to men with specific long-known causes of TD and should not be offered to men without those specific conditions. Nguyen and colleagues suggested that low T levels occurred in men without these known conditions ‘‘for no discernable reason other than older age.’’1
The controversy arises because professional society guidelines from prominent medical groups such as the Endocrine Society4 and the American Urological Association,5 as well as clinical recommendations from other groups,6,7 make no such distinction based on etiology of TD, and recommend treatment for those with characteristic symptoms and/or signs of TD confirmed by low serum T levels.
As Dr. Traish ably explains,2 the biological effects and symptoms of TD occur from reduced levels of T, regardless of underlying etiology. So, it has been perplexing to clinicians and researchers alike why the FDA would take the position that a man with a pituitary tumor and a low serum T level would merit treatment, but a man without a pituitary tumor would not merit treatment, even with identical symptoms and serum T levels.
*The FDA is a critically important government institution charged with the protection of our public health. Yet it must be emphasized that its role is to regulate the pharmaceutical industry, and not health care providers. It bears emphasis that the FDA is not involved with the practice of medicine. Yet the medical community and insurance companies pay close attention to the FDA’s positions and insurance companies frequently restrict coverage based on FDA labels, especially if it helps their bottom line.
Although pressures on a regulatory agency such as the FDA differ substantially from those of health care providers and medical groups, it is to be hoped that the entirety of the scientific community, including the FDA, will soon come to recognize the importance of TTh not only for its symptomatic benefits in men with age-related TD but also for its impact on general health. I encourage everyone interested in TD and its treatment to read the excellent articles by Traish2 and by Nguyen and colleagues.3*
