3rd Annual Jefferson Urology Symposium: Men’s Health Forum

© The Canadian Journal of Urology TM : International Supplement, August 2020 Controversies with testosterone therapy Mohit Khera, MD Department of Urology, Baylor College of Medicine, Houston, Texas, USA KHERAM. Controversies with testosterone therapy. Can J Urol 2020;27(Suppl 3):20-23. Introduction: Over the past decade, there have been concerns with safety of testosterone therapy (TTh) in hypogonadal men. Several concerns have centered on the use of TTh and its potential link to cardiovascular (CV) events, prostate cancer, and benign prostatic hyperplasia (BPH). There has also been controversy in determining which patients are appropriate candidates for TTh and if lifestyle modification has any role in improving serum testosterone values in hypogonadal men. Materials and methods: A literature review of all articles assessing testosterone and the use of TTh and the association with CV events, prostate cancer, BPH and lifestyle modification was conducted. Results: Majority of patients treated with TTh today are treated off-label. Low serum testosterone levels have been associated with increased CV events. Currently, there is inconclusive evidence to support that TTh increases the risk of CV events. There is an absence of evidence linking TTh to the development of prostate cancer or worsening of BPH symptoms. Finally, lifestyle modification, such as decreasing weight and improving sleep, can improve serum testosterone levels in hypogonadal men. Conclusions: Clinicians prescribing testosterone should be aware of the current controversies associated with TTh. The current literature does not suggest that there is a significant risk with TTh and prostate cancer, worsening of BPH symptoms or CV events. However, more studies, including randomized placebo-controlled trials, are needed. Finally, patients should be counseled appropriately regarding the indications for TTh and the benefits of lifestyle modification prior to initiating TTh. KeyWords: testosterone therapy, safety, hypogonadal men Address correspondence to Dr. Mohit Khera, Department of Urology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030 USA Indications for testosterone therapy In 1981, the FDA issued a class labeling change regarding the indications to treat hypogonadal patients. The label at that time stated “Androgens are indicated for replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone.” The label then went on to list certain medical conditions associated with primary and secondary hypogonadism, such as orchitis or pituitary tumor, respectively. Nowhere in the label did it list symptoms, such as erectile dysfunction, low libido, or fatigue, as indications for treatment. However, the label at that time did list “idiopathic” as a one of the potential causes for hypogonadism. Therefore, if a hypogonadal patient did not have a listed medical condition, one could assume that the cause was idiopathic and the 20 patient could be treated on-label. In 2015, the FDA issued a safety announcement stating “The U.S. Food and Drug Administration (FDA) cautions that prescription testosterone products are approved only for men who have low testosterone levels caused by certain medical conditions. The benefit and safety of these medications have not been established for the treatment of low testosterone levels due to aging, even if a man’s symptoms seem related to low testosterone.” As a result of this announcement, the FDArequired that the testosterone label remove the word “idiopathic” under the listed conditions indicated for testosterone therapy (TTh). Thus, hypogonadal patients not having a medical condition known to result in hypogonadism were considered to be treated off-label at this point. Maseroli et al found that roughly 85% of patients being treated with TTh did not have a known medical condition associatedwith hypogonadismand thus they were being treated off-label. 1 Another concern with the indications for TTh is the use of T as monotherapy to treat erectile dysfunction. Current T guidelines recommend the use of TTh in hypogonadal men who