Is Testosterone Being Abused in Middle Age?
- Moderator: Ajay Nehra, MD
- Debater - Pro: Ajay K. Nangia, MD
- Debater - Pro: Jacob Rajfer, MD
- Debater - Con: Martin M. Miner, MD
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Debater - Con: Ridwan Shabsigh, MD
Overview, Ajay Nehra, MD
Dr. Nehra began with an overview of the history of testosterone from the powers attributed to the testes in ancient times to the recent controversy of the use of testosterone in athletics.
Debater - Pro: Ajay K. Nangia, MD
Dr. Nangia argued that testosterone therapy is being abused because of its rapid increase in use in the past decade, poor monitoring, guidelines not being followed, and also a possible increase in risk with treatment. He stated that all age groups in the United States have seen a dramatic increase in use since 2001, but most concerning is the increase in the prescription of testosterone to men of younger age.
He noted that there are guidelines for the therapeutic use of testosterone but argued that they are too open. The FDA guidelines state that testosterone therapies should not be prescribed unless low testosterone levels are associated with a medical condition. Additionally, the guidelines indicate that testosterone levels should be measured for appropriate management of therapy.
Dr. Nangia raised the following concerns: in the United States, there are low-T clinics being run by nonspecialists, and some of these clinics are permitting the purchase of testosterone with cash, so it cannot be tracked. In an analysis of almost 11 million men treated with testosterone over 40 years, it was unknown what percentage of these men had a low testosterone level, and 25% of new users did not have their serum testosterone level measured at treatment onset. Testosterone testing is not increasing with the increase in testosterone initiation. Additionally, more than 73% of men initiating testosterone therapy in the United States had normal serum total testosterone levels before starting treatment.
He then described the cardiovascular risk associated with testosterone treatment, highlighting the findings of the Testosterone in Older Men with Mobility Limitations (TOM) trial: there was an increased number of cardiovascular events in men treated with testosterone, so the trial was stopped early. In a meta-analysis of cardiovascular events, there were more cardiovascular events in older men receiving testosterone replacement therapy. Additionally, in the meta-analysis, the risk for cardiovascular events increased in non-pharma trials over that of pharma trials. Citing the work of Vigen et al.,1 Dr. Nangia noted that an association has been found between testosterone therapy and mortality, myocardial infarction, and stroke.
Dr. Nangia argued that testosterone is being overprescribed and should be given for symptoms and low testosterone levels, as per guidelines. Additionally, he strongly advocated for appropriate monitoring of patient serum testosterone levels and raised the point that the long-term safety of testosterone use is unclear, especially given the recent data suggesting cardiovascular risk.
Debater - Con: Martin M. Miner, MD
Dr. Miner argued that when used according to The Endocrine Society guidelines2 from 2010, testosterone is not being abused nor overdiagnosed. He suggested that testosterone might be underused, but there are no data to show this yet, and that testosterone may have more benefits than currently recognized in terms of cognition, mood, and the reduction of bone fractures. He stated that there is no evidence for cardiovascular adverse events.
Dr. Miner acknowledged that there has been an increase in testosterone sales, but suggested that this does not imply overprescription.
Citing The Endocrine Society guidelines from 2010, Dr. Miner noted that the “right patient” must be treated and that this must be determined by 2 measurements of serum testosterone levels and evaluation of symptoms. Appropriate follow-up should involve additional serum testosterone level measurements as well as hematocrit testing. He said that testosterone levels should be repleted to midrange levels.
He went on to address the concerns regarding cardiovascular risk associated with testosterone. On the basis of the raw data from the study by Vigen et al.,1 he cited an incidence of mortality, myocardial infarction, and stroke in 21.2% of patients who did not receive testosterone therapy, compared with 10.0% of patients who received testosterone. Dr. Miner stated that these data cannot be generalized to all men because these patients underwent cardiac catheterization. These data differ greatly from the adjusted values reported in the abstract of the study because no standardized method was used to assign statistical weights.
Regarding the study by Finkle et al.,3 Dr. Miner noted that this was a retrospective cohort study of a healthcare insurance claims database, and that the choice of a comparison group treated with a phosphodiesterase type 5 inhibitor may have been inappropriate. He questioned the substantiality of an additional 1.27 myocardial infarctions in 1000 years of exposure to testosterone.
In response to the findings of the TOM study, Dr. Miner highlighted the fact that the starting doses of testosterone used were higher than those recommended by the drug manufacturer, so inadvertent oversupplementation may have occurred.
He also cited studies that have linked low testosterone levels with increased mortality risk, and restoration of testosterone with decreased mortality risk.
Dr. Miner argued that a registry is needed to assess cardiac events, and that a randomized controlled trial comparing testosterone vs placebo should be performed to determine the effect of treatment on safety outcomes.
Debater - Pro: Jacob Rajfer, MD
Dr. Raifer emphasized that treatment of a patient without close monitoring can constitute abuse, and he noted that many antiaging clinics, not typically run by urologists, are providing patients with prescriptions for testosterone without adequate monitoring of their serum levels or appropriate follow-up.
Dr. Raifer also noted that many of the studies examining the effects of testosterone on cardiovascular disease have not been appropriately powered, but stated that the cost of such a study may be prohibitive. However, he suggested that caution should be applied regarding the association between cardiovascular disease and testosterone treatment because 2 recent studies have shown an increased risk, after application of statistical weighting to normalize between the groups.
Debater - Con: Ridwan Shabsigh, MD
Dr. Shabsigh argued that testosterone is being underused, not abused. In a 5-year observational study, testosterone replacement therapy was found to decrease body weight, waist circumference, and body mass index.4 Additionally, he cited the benefits of testosterone in metabolic syndrome,4 diabetes,5 osteoporosis,6 and benign prostatic hyperplasia/lower urinary tract symptoms.7
He stated that the cardiovascular risk associated with testosterone has not yet been proven, and in comparison to the high prevalence of hypogonadism, he suggested that testosterone therapy is underused.
Summary, Ajay Nehra, MD
Dr. Nehra stated that there is clearly a lot of debate regarding testosterone treatment. He highlighted the need for further trials to determine the risks associated with testosterone replacement therapy.
References
- Vigen R, O'Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310(17):1829-1836.
- Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536-2559.
- Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014;9(1):e85805.
- Yassin DJ, Doros G, Hammerer PG, Yassin AA. Long-term testosterone treatment in elderly men with hypogonadism and erectile dysfunction reduces obesity parameters and improves metabolic syndrome and health-related quality of life. J Sex Med. 2014 Apr 8 [Epub ahead of print].
- Haider A, Yassin A, Doros G, Saad F. Effects of long-term testosterone therapy on patients with "diabesity": results of observational studies of pooled analyses in obese hypogonadal men with type 2 diabetes. Int J Endocrinol. 2014;2014:683515.
- Haider A, Meergans U, Traish A. Progressive improvement of T-scores in men with osteoporosis and subnormal serum testosterone levels upon treatment with testosterone over six years. Int J Endocrinol. 2014;2014:496948.
- Yassin DJ, El Douaihy Y, Yassin AA, Kashanian J, Shabsigh R, Hammerer PG. Lower urinary tract symptoms improve with testosterone replacement therapy in men with late-onset hypogonadism: 5-year prospective, observational and longitudinal registry study. World J Urol. 2013 Oct 18 [Epub ahead of print].