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Knowledge is Power
613
EDITORIAL Knowledge is Power
Seize every opportunity along the way, for how sad it would be if the road you chose became the road not taken.
As Editor-in-Chief of our extraordinarily special publication, The Journal of Sexual Medicine ( JSM), I am honoring freelance writer Robert Brault and taking that road. I am proudly writing this editorial to publicly discuss what I believe to be a highly impactful article that is considered by many to be ill-conceived and filled with conclusions that simply do not make sense. I feel it is important to discuss and challenge this now. It is my duty and responsibility to speak out here. My motivation is the well-being of and management opportunities for all of our patients. Being silent is not an option. Knowledge is power. Let me share an anecdote showing the true clinical impact of published data. A long-time patient of mine, now 59 years old, contacted me. His erectile dysfunction had been successfully treated, in part by oral PDE5 inhibitors, and his hypogonadal symptoms of fatigue, low energy, depressive symptoms, low sexual drive, variable erectile function, and general malaise had been successfully managed by daily administration of transdermal testosterone therapy. Recent follow-up blood tests of total and free testosterone had returned results in the middle tertile of the normal range. He also had occasional angina secondary to underlying coronary artery disease that had been treated, in part, by multiple drug-eluting stents in the right and left coronary arteries. He contacted me with urgency in his voice because his cardiologist wanted him to immediately stop the testosterone treatment based on data from a new article in The Journal of the American Medical Association ( JAMA) claiming testosterone was dangerous in men with coronary artery disease [1]. His wife became extremely distressed that he was taking the testosterone. I told him that the information published was contrary to previous evidence on the use of testosterone treatment in men with hypogonadism and promised to speak with his cardiologist. Despite my short conversation with his busy cardiologist, the patient made the decision to stop his testosterone treatment. As of this editorial, he still remains off testosterone treatment, with many of © 2014 International Society for Sexual Medicine
the hypogonadal symptoms returning, especially low energy, fatigue, and general malaise. The same day, a 55-year-old ophthalmologist patient of mine with low sexual drive and hypogonadism called me to tell me he would no longer take testosterone treatment because of a recent publication on the negative effects of testosterone that was “all over the media” [2]. He too remains off testosterone treatment. Four other patients on testosterone either called or sent e-mails expressing concerns over their testosterone therapy. That same afternoon I arrived at the monthly Sexual Medicine Rounds at Alvarado Hospital, and before I even started to lecture, a colleague in the audience raised his hand to ask for my take on the new JAMA article and my thoughts concerning the safety of testosterone therapy. By day’s end I was too was reading in multiple media outlets about this new JAMA article [3] espousing what I thought to be unusual data: that testosterone was associated with a higher risk of death, heart attack, and stroke. Author Gertrude Stein wrote, “Everybody gets so much information all day long that they lose their common sense.” Given the daily barrage of information, often coming through media sound bites, it is our responsibility to make sense of new data that may affect our patients—especially as in this case the data from the JAMA article simply did not make sense to me and many of my colleagues. The new JAMA data differ greatly from what has been published for years in the JSM and other journals. Knowledge is power. There are numerous epidemiologic studies in the JSM and in other journals showing correlation between low testosterone levels and sexual dysfunctions such as low libido and decreased erectile function. There are multiple epidemiologic studies showing correlations between low testosterone levels and multiple metabolic diseases, such as cardiovascular disease, diabetes mellitus, hypertension, hypercholesterolemia, obesity, and metabolic syndrome. There are also prospective studies showing that treatments with biologically available testosterone may improve diabetes mellitus, hypertension, hypercholesterolemia, and metabolic syndrome. Furthermore, the risks realized in those J Sex Med 2014;11:613–615
614 patients in prospective placebo-controlled studies did not include early death, myocardial infarction, or stroke [4–27]. There is no question that we need large, multiinstitutional, long-term, placebo-controlled, prospective safety and efficacy data on testosterone treatment in hypogonadal men, especially with regard to morbidity and mortality concerns. But was the recent JAMA article [1] such a prospective investigation? I needed to know more than the sound bite. I needed to understand how the article in question came to such very different conclusions about the risks of testosterone treatment. When I finally had the opportunity to read “Association of Testosterone Therapy with Mortality, Myocardial Infarction, and Stroke in Men with Low Testosterone Levels” [1] later that day, I was struck by several disconcerting observations concerning the study design. I reread the article five times that evening, as it is actually a very complicated study, with approximately 50 different variables studied. First, the study by Vigen and colleagues was a very statistically oriented study, not a classic double-blind, placebo-controlled, prospective study of the type from which clinical conclusions are traditionally fashioned. This was a retrospective, observational study of men who had had significant health concerns—that is, they had undergone a coronary angiography procedure. I was then struck by the treatment testosterone level. This value was only 332 ng/dL, and that did not seem to be very therapeutic, being far below what most of us consider a good target value post-treatment. Other methodological issues with the study were also noted. Subjects were not randomized to testosterone treatment vs. no testosterone treatment. The most frequent testosterone treatment prescribed was the testosterone patch, and in my clinical experience, there is poor compliance with this delivery system because of allergic reactions to the patch adhesive. In addition, the conclusions of this team of authors seemed unrealistic, as they were based on testosterone use even though 17% of treatment patients filled their prescriptions for testosterone only once. That level of minimal treatment exposure to testosterone is simply insufficient to make conclusions concerning serious health risks. Further, there was no evidence that patients assigned to testosterone treatment were actually compliant with their testosterone, as none of these patients were contacted. And why were follow-up J Sex Med 2014;11:613–615
Editorial testosterone levels measured in only 60% of treated men? There were no follow-up testosterone measurements over time. Another interesting negative aspect of this study was that the median starting time of testosterone treatment after the coronary angiogram was approximately 1.5 years later. The mean time after the start of testosterone treatment was actually less than a year. This time period is insufficient for one to be able to draw conclusions about the definitive risk or benefit of testosterone therapy. The current consensus definition of the diagnosis of hypogonadism is a combination of (i) low testosterone blood levels and (ii) concurrent clinical symptoms of androgen deficiency. In the JAMA publication, the diagnosis of hypogonadism was based solely on blood levels of testosterone as determined by assays that, incidentally, were not performed in a central laboratory but in a variety of laboratories. The article in question is not simply a poorly conceived and poorly designed study. The data do not reflect current data from prospective studies. While new studies with new data will always be valued, that value will be based on the quality of the research. As a clinician, I felt compelled to write about this highly clinically impactful article (as measured by the intense media exposure) because of patient fear resulting in withdrawal from therapy. If you are interested in investigating further, please read the accompanying invited commentary, “Death by Testosterone? We Think Not!” More than 20 recognized international experts in testosterone treatment for use in hypogonadal patients have signed this document. Knowledge is power. Now, when patients and health-care providers ask me about the benefits and dangers of testosterone treatment based on the newly published article, I provide them with multiple other publications of prospective and placebo-controlled research and let them draw their own conclusions. Knowledge is power. With this editorial and the accompanying commentary, The Journal of Sexual Medicine has taken an important stand in the field of sexual medicine. For the record, a PubMed search of articles published in 2013 with the keyword “testosterone” returned 5 articles in JAMA and 46 in your JSM. The JSM represents the field. The JSM represents the experts in testosterone and sexual medicine. While we are all awaiting carefully designed, long-term, multi-institutional, placebo-controlled,
615
Editorial prospective safety and efficacy data on testosterone treatment in men with hypogonadism, we will not remain silent concerning the clinical implications of an article that simply does not make sense and that interferes with sexual medicine patients’ treatment confidence. Knowledge is power. Please read your JSM to gain the knowledge. Cite your journal regularly. Review for it and write for it. We can all make a difference. In the end, our patients who are bothered by sexual health concerns rely upon our knowledge of good clinical data to help make important and meaningful sexual medicine management choices. Irwin Goldstein, MD References 1 Vigen R, O’Donnell CI, Barón AE, Grunwald GK, Maddox TM, Bradley SM, Barqawi A, Woning G, Wierman ME, Plomondon ME, Rumsfeld JS, Ho PM. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA 2013;310:1829–36. 2 Beck M. Testosterone therapy tied to heart risks. Wall Street Journal, November 5, 2013. Available at: http://online.wsj .com/news/articles/SB10001424052702303661404579180294 201174958 (accessed January 4, 2014). 3 Kim J. Testosterone therapy raises heart and death risks, study finds. Everyday Health, November 5, 2013. http://www .everydayhealth.com/low-testosterone/testosterone-therapy -raises-heart-and-death-risks-study-finds.aspx (accessed January 4, 2014). 4 Corona G, Rastrelli G, Maggi M. Diagnosis and treatment of late-onset hypogonadism: Systematic review and meta-analysis of TRT outcomes. Best Pract Res Clin Endocrinol Metab 2013;27:557–79. 5 Isidori AM, Buvat J, Corona G, Goldstein I, Jannini EA, Lenzi A, Porst H, Salonia A, Traish AM, Maggi M. A critical analysis of the role of testosterone in erectile function: From pathophysiology to treatment—a systematic review. Eur Urol 2014;65:99–112. 6 Francomano D, Ilacqua A, Bruzziches R, Lenzi A, Aversa A. Effects of 5-year treatment with testosterone undecanoate on lower urinary tract symptoms in obese men with hypogonadism and metabolic syndrome. Urology 2014;83:167–74. 7 Muraleedharan V, Marsh H, Kapoor D, Channer KS, Jones TH. Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Eur J Endocrinol 2013;169:725–33. 8 Hackett G, Cole N, Bhartia M, Kennedy D, Raju J, Wilkinson P. Testosterone replacement therapy with long-acting testosterone undecanoate improves sexual function and quality-oflife parameters versus placebo in a population of men with type 2 diabetes. J Sex Med 2013;10:1612–27. 9 Morales A. The long and tortuous history of the discovery of testosterone and its clinical application. J Sex Med 2013;10: 1178–83. 10 Corona G, Rastrelli G, Ricca V, Jannini EA, Vignozzi L, Monami M, Sforza A, Forti G, Mannucci E, Maggi M. Risk factors associated with primary and secondary reduced libido in male patients with sexual dysfunction. J Sex Med 2013;10:1074–89.
11 Buvat J, Maggi M, Guay A, Torres LO. Testosterone deficiency in men: Systematic review and standard operating procedures for diagnosis and treatment. J Sex Med 2013;10:245–84. 12 Rubio-Aurioles E, Bivalacqua TJ. Standard operational procedures for low sexual desire in men. J Sex Med 2013;10:94–107. 13 Zitzmann M, Mattern A, Hanisch J, Gooren L, Jones H, Maggi M. IPASS: A study on the tolerability and effectiveness of injectable testosterone undecanoate for the treatment of male hypogonadism in a worldwide sample of 1438 men. J Sex Med 2013;10:579–88. 14 Kaufman JM, Miller MG, Fitzpatrick S, McWhirter C, Brennan JJ. One-year efficacy and safety study of a 1.62% testosterone gel in hypogonadal men: Results of a 182-day open-label extension of a 6-month double-blind study. J Sex Med 2012;9:1149–61. 15 Corona G, Gacci M, Baldi E, Mancina R, Forti G, Maggi M. Androgen deprivation therapy in prostate cancer: Focusing on sexual side effects. J Sex Med 2012;9:887–902. 16 Di Sante S, Conners WP, Morgentaler A. Influence of baseline serum testosterone on changes in body composition in response to testosterone therapy. J Sex Med 2012;9:585–93. 17 Khera M, Bhattacharya RK, Blick G, Kushner H, Nguyen D, Miner MM. Improved sexual function with testosterone replacement therapy in hypogonadal men: Real-world data from the Testim Registry in the United States (TRiUS). J Sex Med 2011;8:3204–13. 18 Corona G, Rastrelli G, Forti G, Maggi M. Update in testosterone therapy for men. J Sex Med 2011;8:639–54. 19 Lin JW, Lee JK, Wu CK, Caffrey JL, Chang MH, Hwang JJ, Dowling N, Lin YS. Metabolic syndrome, testosterone, and cardiovascular mortality in men. J Sex Med 2011;8:2350–60. 20 Carson CC III, Rosano G. Exogenous testosterone, cardiovascular events, and cardiovascular risk factors in elderly men: A review of trial data. J Sex Med 2012;9:54–67. 21 Corona G, Rastrelli G, Monami M, Melani C, Balzi D, Sforza A, Forti G, Mannucci E, Maggi M. Body mass index regulates hypogonadism-associated CV risk: Results from a cohort of subjects with erectile dysfunction. J Sex Med 2011;8:2098–105. 22 Kaufman JM, Miller MG, Garwin JL, Fitzpatrick S, McWhirter C, Brennan JJ. Efficacy and safety study of 1.62% testosterone gel for the treatment of hypogonadal men. J Sex Med 2011;8:2079–89. 23 Corona G, Monami M, Rastrelli G, Aversa A, Tishova Y, Saad F, Lenzi A, Forti G, Mannucci E, Maggi M. Testosterone and metabolic syndrome: A meta-analysis study. J Sex Med 2011;8:272–83. 24 Permpongkosol S, Tantirangsee N, Ratana-olarn K. Treatment of 161 men with symptomatic late onset hypogonadism with long-acting parenteral testosterone undecanoate: Effects on body composition, lipids, and psychosexual complaints. J Sex Med 2010;7:3765–74. 25 Traish AM, Gooren LJ. Safety of physiological testosterone therapy in women: Lessons from female-to-male transsexuals (FMT) treated with pharmacological testosterone therapy. J Sex Med 2010;7:3758–64. 26 Buvat J, Montorsi F, Maggi M, Porst H, Kaipia A, Colson MH, Cuzin B, Moncada I, Martin-Morales A, Yassin A, Meuleman E, Eardley I, Dean JD, Shabsigh R. Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1% hydroalcoholic testosterone gel in the treatment of erectile dysfunction (TADTEST study). J Sex Med 2011;8:284–93. 27 Aversa A, Bruzziches R, Francomano D, Rosano G, Isidori AM, Lenzi A, Spera G. Effects of testosterone undecanoate on cardiovascular risk factors and atherosclerosis in middle-aged men with late-onset hypogonadism and metabolic syndrome: Results from a 24-month, randomized, double-blind, placebocontrolled study. J Sex Med 2010;7:3495–503.
J Sex Med 2014;11:613–615
EDITORIAL Knowledge is Power
Seize every opportunity along the way, for how sad it would be if the road you chose became the road not taken.
As Editor-in-Chief of our extraordinarily special publication, The Journal of Sexual Medicine ( JSM), I am honoring freelance writer Robert Brault and taking that road. I am proudly writing this editorial to publicly discuss what I believe to be a highly impactful article that is considered by many to be ill-conceived and filled with conclusions that simply do not make sense. I feel it is important to discuss and challenge this now. It is my duty and responsibility to speak out here. My motivation is the well-being of and management opportunities for all of our patients. Being silent is not an option. Knowledge is power. Let me share an anecdote showing the true clinical impact of published data. A long-time patient of mine, now 59 years old, contacted me. His erectile dysfunction had been successfully treated, in part by oral PDE5 inhibitors, and his hypogonadal symptoms of fatigue, low energy, depressive symptoms, low sexual drive, variable erectile function, and general malaise had been successfully managed by daily administration of transdermal testosterone therapy. Recent follow-up blood tests of total and free testosterone had returned results in the middle tertile of the normal range. He also had occasional angina secondary to underlying coronary artery disease that had been treated, in part, by multiple drug-eluting stents in the right and left coronary arteries. He contacted me with urgency in his voice because his cardiologist wanted him to immediately stop the testosterone treatment based on data from a new article in The Journal of the American Medical Association ( JAMA) claiming testosterone was dangerous in men with coronary artery disease [1]. His wife became extremely distressed that he was taking the testosterone. I told him that the information published was contrary to previous evidence on the use of testosterone treatment in men with hypogonadism and promised to speak with his cardiologist. Despite my short conversation with his busy cardiologist, the patient made the decision to stop his testosterone treatment. As of this editorial, he still remains off testosterone treatment, with many of © 2014 International Society for Sexual Medicine
the hypogonadal symptoms returning, especially low energy, fatigue, and general malaise. The same day, a 55-year-old ophthalmologist patient of mine with low sexual drive and hypogonadism called me to tell me he would no longer take testosterone treatment because of a recent publication on the negative effects of testosterone that was “all over the media” [2]. He too remains off testosterone treatment. Four other patients on testosterone either called or sent e-mails expressing concerns over their testosterone therapy. That same afternoon I arrived at the monthly Sexual Medicine Rounds at Alvarado Hospital, and before I even started to lecture, a colleague in the audience raised his hand to ask for my take on the new JAMA article and my thoughts concerning the safety of testosterone therapy. By day’s end I was too was reading in multiple media outlets about this new JAMA article [3] espousing what I thought to be unusual data: that testosterone was associated with a higher risk of death, heart attack, and stroke. Author Gertrude Stein wrote, “Everybody gets so much information all day long that they lose their common sense.” Given the daily barrage of information, often coming through media sound bites, it is our responsibility to make sense of new data that may affect our patients—especially as in this case the data from the JAMA article simply did not make sense to me and many of my colleagues. The new JAMA data differ greatly from what has been published for years in the JSM and other journals. Knowledge is power. There are numerous epidemiologic studies in the JSM and in other journals showing correlation between low testosterone levels and sexual dysfunctions such as low libido and decreased erectile function. There are multiple epidemiologic studies showing correlations between low testosterone levels and multiple metabolic diseases, such as cardiovascular disease, diabetes mellitus, hypertension, hypercholesterolemia, obesity, and metabolic syndrome. There are also prospective studies showing that treatments with biologically available testosterone may improve diabetes mellitus, hypertension, hypercholesterolemia, and metabolic syndrome. Furthermore, the risks realized in those J Sex Med 2014;11:613–615
614 patients in prospective placebo-controlled studies did not include early death, myocardial infarction, or stroke [4–27]. There is no question that we need large, multiinstitutional, long-term, placebo-controlled, prospective safety and efficacy data on testosterone treatment in hypogonadal men, especially with regard to morbidity and mortality concerns. But was the recent JAMA article [1] such a prospective investigation? I needed to know more than the sound bite. I needed to understand how the article in question came to such very different conclusions about the risks of testosterone treatment. When I finally had the opportunity to read “Association of Testosterone Therapy with Mortality, Myocardial Infarction, and Stroke in Men with Low Testosterone Levels” [1] later that day, I was struck by several disconcerting observations concerning the study design. I reread the article five times that evening, as it is actually a very complicated study, with approximately 50 different variables studied. First, the study by Vigen and colleagues was a very statistically oriented study, not a classic double-blind, placebo-controlled, prospective study of the type from which clinical conclusions are traditionally fashioned. This was a retrospective, observational study of men who had had significant health concerns—that is, they had undergone a coronary angiography procedure. I was then struck by the treatment testosterone level. This value was only 332 ng/dL, and that did not seem to be very therapeutic, being far below what most of us consider a good target value post-treatment. Other methodological issues with the study were also noted. Subjects were not randomized to testosterone treatment vs. no testosterone treatment. The most frequent testosterone treatment prescribed was the testosterone patch, and in my clinical experience, there is poor compliance with this delivery system because of allergic reactions to the patch adhesive. In addition, the conclusions of this team of authors seemed unrealistic, as they were based on testosterone use even though 17% of treatment patients filled their prescriptions for testosterone only once. That level of minimal treatment exposure to testosterone is simply insufficient to make conclusions concerning serious health risks. Further, there was no evidence that patients assigned to testosterone treatment were actually compliant with their testosterone, as none of these patients were contacted. And why were follow-up J Sex Med 2014;11:613–615
Editorial testosterone levels measured in only 60% of treated men? There were no follow-up testosterone measurements over time. Another interesting negative aspect of this study was that the median starting time of testosterone treatment after the coronary angiogram was approximately 1.5 years later. The mean time after the start of testosterone treatment was actually less than a year. This time period is insufficient for one to be able to draw conclusions about the definitive risk or benefit of testosterone therapy. The current consensus definition of the diagnosis of hypogonadism is a combination of (i) low testosterone blood levels and (ii) concurrent clinical symptoms of androgen deficiency. In the JAMA publication, the diagnosis of hypogonadism was based solely on blood levels of testosterone as determined by assays that, incidentally, were not performed in a central laboratory but in a variety of laboratories. The article in question is not simply a poorly conceived and poorly designed study. The data do not reflect current data from prospective studies. While new studies with new data will always be valued, that value will be based on the quality of the research. As a clinician, I felt compelled to write about this highly clinically impactful article (as measured by the intense media exposure) because of patient fear resulting in withdrawal from therapy. If you are interested in investigating further, please read the accompanying invited commentary, “Death by Testosterone? We Think Not!” More than 20 recognized international experts in testosterone treatment for use in hypogonadal patients have signed this document. Knowledge is power. Now, when patients and health-care providers ask me about the benefits and dangers of testosterone treatment based on the newly published article, I provide them with multiple other publications of prospective and placebo-controlled research and let them draw their own conclusions. Knowledge is power. With this editorial and the accompanying commentary, The Journal of Sexual Medicine has taken an important stand in the field of sexual medicine. For the record, a PubMed search of articles published in 2013 with the keyword “testosterone” returned 5 articles in JAMA and 46 in your JSM. The JSM represents the field. The JSM represents the experts in testosterone and sexual medicine. While we are all awaiting carefully designed, long-term, multi-institutional, placebo-controlled,
615
Editorial prospective safety and efficacy data on testosterone treatment in men with hypogonadism, we will not remain silent concerning the clinical implications of an article that simply does not make sense and that interferes with sexual medicine patients’ treatment confidence. Knowledge is power. Please read your JSM to gain the knowledge. Cite your journal regularly. Review for it and write for it. We can all make a difference. In the end, our patients who are bothered by sexual health concerns rely upon our knowledge of good clinical data to help make important and meaningful sexual medicine management choices. Irwin Goldstein, MD References 1 Vigen R, O’Donnell CI, Barón AE, Grunwald GK, Maddox TM, Bradley SM, Barqawi A, Woning G, Wierman ME, Plomondon ME, Rumsfeld JS, Ho PM. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA 2013;310:1829–36. 2 Beck M. Testosterone therapy tied to heart risks. Wall Street Journal, November 5, 2013. Available at: http://online.wsj .com/news/articles/SB10001424052702303661404579180294 201174958 (accessed January 4, 2014). 3 Kim J. Testosterone therapy raises heart and death risks, study finds. Everyday Health, November 5, 2013. http://www .everydayhealth.com/low-testosterone/testosterone-therapy -raises-heart-and-death-risks-study-finds.aspx (accessed January 4, 2014). 4 Corona G, Rastrelli G, Maggi M. Diagnosis and treatment of late-onset hypogonadism: Systematic review and meta-analysis of TRT outcomes. Best Pract Res Clin Endocrinol Metab 2013;27:557–79. 5 Isidori AM, Buvat J, Corona G, Goldstein I, Jannini EA, Lenzi A, Porst H, Salonia A, Traish AM, Maggi M. A critical analysis of the role of testosterone in erectile function: From pathophysiology to treatment—a systematic review. Eur Urol 2014;65:99–112. 6 Francomano D, Ilacqua A, Bruzziches R, Lenzi A, Aversa A. Effects of 5-year treatment with testosterone undecanoate on lower urinary tract symptoms in obese men with hypogonadism and metabolic syndrome. Urology 2014;83:167–74. 7 Muraleedharan V, Marsh H, Kapoor D, Channer KS, Jones TH. Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Eur J Endocrinol 2013;169:725–33. 8 Hackett G, Cole N, Bhartia M, Kennedy D, Raju J, Wilkinson P. Testosterone replacement therapy with long-acting testosterone undecanoate improves sexual function and quality-oflife parameters versus placebo in a population of men with type 2 diabetes. J Sex Med 2013;10:1612–27. 9 Morales A. The long and tortuous history of the discovery of testosterone and its clinical application. J Sex Med 2013;10: 1178–83. 10 Corona G, Rastrelli G, Ricca V, Jannini EA, Vignozzi L, Monami M, Sforza A, Forti G, Mannucci E, Maggi M. Risk factors associated with primary and secondary reduced libido in male patients with sexual dysfunction. J Sex Med 2013;10:1074–89.
11 Buvat J, Maggi M, Guay A, Torres LO. Testosterone deficiency in men: Systematic review and standard operating procedures for diagnosis and treatment. J Sex Med 2013;10:245–84. 12 Rubio-Aurioles E, Bivalacqua TJ. Standard operational procedures for low sexual desire in men. J Sex Med 2013;10:94–107. 13 Zitzmann M, Mattern A, Hanisch J, Gooren L, Jones H, Maggi M. IPASS: A study on the tolerability and effectiveness of injectable testosterone undecanoate for the treatment of male hypogonadism in a worldwide sample of 1438 men. J Sex Med 2013;10:579–88. 14 Kaufman JM, Miller MG, Fitzpatrick S, McWhirter C, Brennan JJ. One-year efficacy and safety study of a 1.62% testosterone gel in hypogonadal men: Results of a 182-day open-label extension of a 6-month double-blind study. J Sex Med 2012;9:1149–61. 15 Corona G, Gacci M, Baldi E, Mancina R, Forti G, Maggi M. Androgen deprivation therapy in prostate cancer: Focusing on sexual side effects. J Sex Med 2012;9:887–902. 16 Di Sante S, Conners WP, Morgentaler A. Influence of baseline serum testosterone on changes in body composition in response to testosterone therapy. J Sex Med 2012;9:585–93. 17 Khera M, Bhattacharya RK, Blick G, Kushner H, Nguyen D, Miner MM. Improved sexual function with testosterone replacement therapy in hypogonadal men: Real-world data from the Testim Registry in the United States (TRiUS). J Sex Med 2011;8:3204–13. 18 Corona G, Rastrelli G, Forti G, Maggi M. Update in testosterone therapy for men. J Sex Med 2011;8:639–54. 19 Lin JW, Lee JK, Wu CK, Caffrey JL, Chang MH, Hwang JJ, Dowling N, Lin YS. Metabolic syndrome, testosterone, and cardiovascular mortality in men. J Sex Med 2011;8:2350–60. 20 Carson CC III, Rosano G. Exogenous testosterone, cardiovascular events, and cardiovascular risk factors in elderly men: A review of trial data. J Sex Med 2012;9:54–67. 21 Corona G, Rastrelli G, Monami M, Melani C, Balzi D, Sforza A, Forti G, Mannucci E, Maggi M. Body mass index regulates hypogonadism-associated CV risk: Results from a cohort of subjects with erectile dysfunction. J Sex Med 2011;8:2098–105. 22 Kaufman JM, Miller MG, Garwin JL, Fitzpatrick S, McWhirter C, Brennan JJ. Efficacy and safety study of 1.62% testosterone gel for the treatment of hypogonadal men. J Sex Med 2011;8:2079–89. 23 Corona G, Monami M, Rastrelli G, Aversa A, Tishova Y, Saad F, Lenzi A, Forti G, Mannucci E, Maggi M. Testosterone and metabolic syndrome: A meta-analysis study. J Sex Med 2011;8:272–83. 24 Permpongkosol S, Tantirangsee N, Ratana-olarn K. Treatment of 161 men with symptomatic late onset hypogonadism with long-acting parenteral testosterone undecanoate: Effects on body composition, lipids, and psychosexual complaints. J Sex Med 2010;7:3765–74. 25 Traish AM, Gooren LJ. Safety of physiological testosterone therapy in women: Lessons from female-to-male transsexuals (FMT) treated with pharmacological testosterone therapy. J Sex Med 2010;7:3758–64. 26 Buvat J, Montorsi F, Maggi M, Porst H, Kaipia A, Colson MH, Cuzin B, Moncada I, Martin-Morales A, Yassin A, Meuleman E, Eardley I, Dean JD, Shabsigh R. Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1% hydroalcoholic testosterone gel in the treatment of erectile dysfunction (TADTEST study). J Sex Med 2011;8:284–93. 27 Aversa A, Bruzziches R, Francomano D, Rosano G, Isidori AM, Lenzi A, Spera G. Effects of testosterone undecanoate on cardiovascular risk factors and atherosclerosis in middle-aged men with late-onset hypogonadism and metabolic syndrome: Results from a 24-month, randomized, double-blind, placebocontrolled study. J Sex Med 2010;7:3495–503.
J Sex Med 2014;11:613–615