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2020, Number 2

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Rev Cuba Endoc 2020; 31 (2)

Late-onset hypogonadism treatment with testosterone

Monteagudo PG, Hernández RM, Gómez AM, Ovies CG

Language: Spanish
References: 87
Page: 1-23
PDF size: 289.44 Kb.


ABSTRACT

Introduction: The use of testosterone replacement therapy in older men has increased in recent years, which has generated multiple controversies not yet resolved about its benefits and potential risks, especially those related to the development or worsening of the prostate or cardiovascular disease.
Methods: A literature review was conducted with the aim of offering a state of the art that helps clinicians make decisions when considering testosterone treatment in patients with late-onset hypogonadism. The information search was carried out with the Google Scholar, Medline and Pubmed search engines.
Conclusions: Testosterone treatment in late-onset hypogonadism is safe, rational, and evidence-based, but it is not recommended to offer it to all older men with low serum testosterone levels. It is advised in those with overt symptoms of androgen deficiency, without active prostate, breast or liver cancer, elevated hematocrit, benign prostatic hyperplasia with severe obstructive symptoms, untested prostate nodule or induration, prostate specific antigen> 4 ng / mL (or > 3 ng / mL in high-risk patients), severe untreated obstructive sleep apnea, short-term fertility wishes, uncontrolled heart failure, acute myocardial infarction or stroke in the last SIX months, or thrombophilia. It is recommended to carry out quarterly monitoring during the first year and then according to each case, which includes evaluation of the clinical response, of conditions that can be aggravated by treatment, and of laboratory parameters.


REFERENCES

  1. Morgentaler A, Zitzmann M, Traish AM, Fox AW, Jones TH, Maggi M, et al. Fundamental concepts regarding testosterone deficiency and treatment: International expert consensus resolutions. Mayo Clin Proc. 2016;91(7):881-96. DOI: 10.1016/j.mayocp.2016.04.007

  2. Bhasin SH, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, et al. Testosterone Therapy in Men with Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715-44.

  3. Mulhall JP, Trost LW, Brannigan RE, Kurtz EJ, Redmon JB, Chiles KA, et al. Evaluation and Management of Testosterone Deficiency: AUA Guideline. J Urology. 2018;200:423-32. DOI: 10.1016/j.juro.2018.03.115

  4. Dean JD, McMahon CG, Guay AT, Morgentaler A, Althof SE, Becher EF, et al. The International Society for Sexual Medicine's Process of Care for the Assessment and Management of Testosterone Deficiency in Adult Men. J Sex Med. 2015;12:1660-86.

  5. Lunenfeld B, Mskhalaya G, Zitzmann M, Arver S, Kalinchenko S, Tishova Y, et al. Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men. Aging Male. 2015;18:5-15.

  6. Traish A. Goldsteinc I. Kimb N. Testosterone and Erectile Function: From Basic Research to a New Clinical Paradigm for Managing Men with Androgen Insufficiency and Erectile Dysfunction. Eur Urol. 2007;52(1):54-70.

  7. Horstman AM, Dillon EL, Urban RJ, Sheffield-Moore M. The role of androgens and estrogens on healthy aging and longevity. J Gerontol A Biol Sci Med Sci. 2012;67(11):1140-52.

  8. Diya K, Emad K, Bayumi S. The clinical relevance of serum testosterone and sexual activity in the ageing male. J Dental Medical Sciences. 2015;14(8):109-16.

  9. Ríos R, Jara N, Ratkman B, Valenzuela A, Palavecino C. Prevalence of Hypogonadism in a Male Population below 60 Years of Age with Metabolic Syndrome. Advances in Andrology. 2015;2015:1-7.

  10. Tang W, Zhuang X, Shu R, Guan D, Ji Y, Zhang B, et al. The prevalence of erectile dysfunction among subjects with late-onset hypogonadism: a population-based study in China. Int J Clin Exp Med. 2015;8(8):13901-10.

  11. Tajar A, Huhtaniemi IT, O'Neill TW, Finn JD, Pye SR, Lee DM, et al. Characteristics of androgen deficiency in late-onset hypogonadism: results from the European Male Aging Study (EMAS). J Clin Endocrinol Metab. 2012;97(5):1508-16.

  12. Celec P, Ostatníková D, Hodosy J. On the effects of testosterone on brain behavioral functions. Rev Neurociencia. 2015;9(12):1-12.

  13. Saad F, Yassin A, Haider A, Doros G, Gooren L. Elderly men over 65 years of age with late-onset hypogonadism benefit as much from testosterone treatment as do younger men. Korean J Urol. 2015;56:310-17.

  14. Jakiel G, Makara M, Ciebiera M, Slabuszewska A. Andropause - state of the art 2015 and review of selected aspects. Prz Menopauzalny. 2015;14(1):1-6.

  15. Lowenstein L, Shechter A, Porst H, Tripodi F, Reisman Y. Physicians' attitudes towards androgen replacement therapy for male and female sexual dysfunction. Int J Impotence Research. 2016; 28:57-61.

  16. Handelsman DJ. Global trends in testosterone prescribing, 2000-2011: expanding the spectrum of prescription drug misuse. Med J Aust. 2013;199(8):548-51.

  17. Bandari J, Ayyash OM, Emery SL, Wessel SB, Davies BJ. Marketing and Testosterone Treatment in the USA: A Systematic Review. Eur Urol Focus. 2017;3:395-402.

  18. Carrasquillo R, Chu K, Ramasamy R. Novel Therapy for Male Hypogonadism. Curr Urol Rep. 2018;19:63-71. DOI: 10.1007/s11934-018-0816

  19. An Q, Gu YQ. Testosterone replacement therapy: dilemmas and challenges in China and Asia. Asian J Androl. 2018;20:149-51.

  20. Saad F, Yassin A, Haider A, Doros G, Gooren L. Elderly men over 65 years of age with late-onset hypogonadism benefit as much from testosterone treatment as do younger men. Korean J Urol 2015;56:310-17.

  21. Aversa A, Morgentaler A. The practical management of testosterone deficiency in men. Nat Rev Urol. 2015;12:641-50.

  22. Sivabalasundaram V, Millar AC. Testosterone replacement therapy in the aging male. CGS Journal of CME. 2015;5(2):2-3.

  23. Khera M. Controversies in testosterone supplementation therapy. Asian J Androl. 2015;17:175-6.

  24. Morgentaler A, Miner MM, Caliber M, Guay AT, Khera M, Traish AM. Testosterone therapy and cardiovascular risk: advances and controversies. Mayo Clin Proc. 2015;90(2):224-51. DOI: 10.1016/j.mayocp.2014.10.011

  25. Morgentaler A, Feibus A, Baum N. Testosterone and cardiovascular disease -the controversy and the facts. Postgrad Med. 2015;127:159-65.

  26. Hwang K, Miner M. Controversies in testosterone replacement therapy: Testosterone and cardiovascular disease. Asian J Androl. 2015;17:187-91.

  27. Morgentaler A. Controversies and advances with testosterone therapy: A 40-year perspective. Urology. 2016;89:27-32.

  28. Saad F, Yassin A, Haider A, Doros G, Gooren L. Elderly men over 65 years of age with late-onset hypogonadism benefit as much from testosterone treatment as do younger men. Korean J Urol. 2015;56:310-7.

  29. Pivonello R, Menafra D, Riccio E, Garifalos F, Mazzella M, de Angelis, et al. Metabolic Disorders and Male Hypogonadotropic Hypogonadism. Front Endocrinol (Lausanne). 2019;10:345-8. DOI: 10.3389/fendo.2019.00345

  30. Guo C, Gu W, Liu M, Peng BO, Yao X, Yang B, et al. Efficacy and safety of testosterone replacement therapy in men with hypogonadism: A meta-analysis study of placebo-controlled trials. Exp Ther Med. 2016;11(3):853-63. DOI: 10.3892/etm.2015.2957

  31. Ponce OJ, Spencer-Bonilla G, Alvarez-Villalobos N, Serrano V, Singh-Ospina N, Rodriguez-Gutierrez R. The Efficacy and Adverse Events of Testosterone Replacement Therapy in Hypogonadal Men: A Systematic Review and Meta-Analysis of Randomized, Placebo-Controlled Trials. J Clin Endocrinol Metab. 2018;103(5):1745-54. DOI: 10.1210/jc.2018-00404

  32. Almehmadi Y, Yassin A, Nettleship J, Saad F. Testosterone replacement therapy improves the health-related quality of life of men diagnosed with late-onset hypogonadism. Arab J Urol. 2016;14(1):31-6.

  33. Coles GE. The Psychological Impact of Testosterone Replacement Therapy in Middle-Aged Men. Walden Dissertations and Doctoral Studies Collection. Walden University. 2019. [acceso: 15/04/2020]. Disponible en: Disponible en: https://pdfs.semanticscholar.org/0741/412501497802d23dfafcd0312eff7675d8e6.pdf?_ga=2.119281353.1933192452.1587025804-1220900639.1587025804

  34. Permpongkosol S, Khupulsup K, Leelaphiwat S, Pavavattananusorn S, Thongpradit S, Petchthong T. Effects of 8-Year Treatment of Long-Acting Testosterone Undecanoate on Metabolic Parameters, Urinary Symptoms, Bone Mineral Density, and Sexual Function in Men with Late-Onset Hypogonadism. J Sex Med. 2016;13(8):1199-211.

  35. Konaka H, Sugimoto K, Orikasa H, Iwamoto T, Takamura T, Takeda Y. Effects of long-term androgen replacement therapy on the physical and mental statuses of aging males with late-onset hypogonadism: a multicenter, randomized controlled trial in Japan. Asian J Androl. 2016;18:25-3.

  36. Yeap BB, Page ST, Grossmann M. Testosterone treatment in older men: clinical implications and unresolved questions from the Testosterone Trials. Lancet Diabetes Endocrinol. 2018;6:659-72. DOI: 10.1016/S2213-8587(17)30416-3

  37. Elliott J, Kelly SE, Millar AC, Peterson J, Chen L, Johnston A, et al. Testosterone therapy in hypogonadal men: a systematic review and network meta-analysis. BMJ Open. 2017;7:e015284. DOI: 10.1136/bmjopen-2016-015284

  38. Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res. 1941;1:293-7.

  39. Huggins C, Stevens RE Jr, Hodges CV. Studies on prostatic cancer. II. The effects of castration on advanced carcinoma of the prostate gland. Arch Surg. 1941;43:209-23.

  40. Dupree JM, Langille GM, Khera M, Lipshultz LI. The safety of testosterone supplementation therapy in prostate cancer. Nat Rev Urol. 2014;11:526-30.

  41. Cui Y, Zong H, Yan H, Zhang Y. The effect of testosterone replacement therapy on prostate cancer: A systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2014;17:132-43.

  42. Baas W, Kohler TS. Testosterone replacement therapy and BPH/LUTS. What is the evidence? Curr Urol Rep. 2016;17:46.

  43. Moore A, Butcher MJ, Köhler TS. Testosterone replacement therapy on the natural history of prostate disease. Curr Urol Rep. 2015;16:51.

  44. Dohle GR, Arver S, Bettocchi C, Jones TH, Kliesch S, Punab M. Guidelines on male hypogonadism. European Association of Urology. 2015 [acceso: 05/08/2019]. Disponible en: Disponible en: http://uroweb.org/wp-content/uploads/18-Male-Hypogonadism_LR1.pdf

  45. Alcántara A. Management of male hypogonadism and testosterone therapy: European Association of Urology position statement on the role of the urologist. Actas Urol Esp. 2018;42(3):212-3. DOI: 10.1016/j.acuro.2017.08.003

  46. Pérez C, Puigvert A, Vargas IB. ¿La disminución en la testosterona sérica es una causa de cáncer de próstata? La hipótesis de Prehn 10 años después. Rev Int Androl. 2008;6:1-3.

  47. Fuentes-Pastor J, Pellejero P, Ortiz I, Ramírez-Backhaus M, de Gracia A, Marrugo C, et al. Asociación del síndrome de hipogonadismo tardío y síndrome metabólico con el cáncer de próstata y su agresividad. Actas Urol Esp. 2016;40(7):440-5. DOI: 10.1016/j.acuro.2016.02.001

  48. Pomerol JM. Evidencias actuales acerca de la relación entre el tratamiento de reemplazo hormonal en el síndrome del déficit de testosterona y el CaP. Rev Int Androl. 2008;6(4):249-54.

  49. Bosco C, Crawley D, Adolfsson J, Rudman S, Hemelrijck VM. Quantifying the Evidence for the Risk of Metabolic Syndrome and Its Components following Androgen Deprivation Therapy for Prostate Cancer: A Meta-Analysis. PLOS ONE. 2015;10(3):1-12.

  50. Miah S, Tharakan T, Gallagher KA, Shah TT, Winkler M, Jayasena CN, et al. The effects of testosterone replacement therapy on the prostate: a clinical perspective. F1000 Research. 2019;8:217-25.

  51. Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, et al. Adverse Events Associated with Testosterone Administration. N Engl J Med. 2010;363:109-22. DOI: 10.1056/NEJMoa1000485

  52. Vigen R, O'Donnell CI, Baron AE, Grunwald G, Maddox TM, Bradley SM, et al. Association of Testosterone Therapy with Mortality, Myocardial Infarction, and Stroke in Men with Low Testosterone Levels. JAMA. 2013;310(17):1829-36. DOI: 10.1001/jama.2013.280386

  53. Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014 [acceso: 05/08/2019];9(1):e85805. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3905977

  54. US Food and Drug Administration. FDA Drug Safety Communication: FDA cautions about using testosterone products for low testosterone due to aging; requires labeling change to inform of possible increased risk of heart attack and stroke with use. 2015. [acceso: 05/08/2019]. Disponible en: Disponible en: https://www.fda.gov/Drugs/DrugSafety/ucm436259.htm

  55. Vigen R, O'Donnell CI, Baron AE, Grunwald G, Maddox TM, Bradley SM, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels (correction). JAMA. 2014;311(9):967.

  56. Kloner RA, Carson C, Dobs A, Kopecky S, Mohler ER. Testosterone and Cardiovascular Disease. J Am Coll Cardiol. 2016;67:545-57. DOI: 10.1016/j.jacc.2015.12.005

  57. Goodman N, Guay A, Dandona P, Dhindsa S, Fajman C, Cunningham GR. American Association of Clinical Endocrinologists and American College of Endocrinology position statement on the association of testosterone and cardiovascular risk. Endocr Pract. 2015;21(9):1066-73.

  58. Francomano D, Bruzziches R, Barbaro G, Lenzi A, Aversa A. Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study. J Endocrinol Invest. 2014; 37(4): 401-11.

  59. Maggi M, Wu FC, Jones TH, Jackson G, Behre HM, Hackett G, et al. Testosterone treatment is not associated with increased risk of adverse cardiovascular events: results from the Registry of Hypogonadism in Men (RHYME). Int J Clin Pract. 2016;70(10):843-52. DOI: 10.1111/ijcp.12876

  60. Traish AM, Haider A, Haider KS, Doros G, Saad F. Long-Term Testosterone Therapy Improves Cardiometabolic Function and Reduces Risk of Cardiovascular Disease in Men with Hypogonadism: A Real-Life Observational Registry Study Setting Comparing Treated and Untreated (Control) Groups. J Cardiovasc Pharmacol Ther. 2017;22(5):414-33. DOI: 10.1177/1074248417691136

  61. Cheetham TC, An JJ, Jacobsen SJ, Niu F, Sidney S, Quesenberry CP, et al. Association of Testosterone Replacement with Cardiovascular Outcomes Among Men with Androgen Deficiency. JAMA Intern Med. 2017;177(4):491-9. DOI: 10.1001/jamainternmed.2016.9546

  62. Wallis CJD, Lo K, Lee Y, Krakowsky Y, Garbens A, Satkunasivam R, et al. Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study. Lancet Diabetes Endocrinol. 2016;4:498-506. DOI: 10.1016/S2213-8587(16)00112-1

  63. Baillargeon J, Urban RJ, Kuo YF, Ottenbacher KJ, Raji MA, Du F, et al. Risk of Myocardial Infarction in Older Men Receiving Testosterone Therapy. Ann Pharmacother. 2014;48(9):1138-44.

  64. Corona G, Maseroli E, Rastrelli G, Isidori AM, Sforza A, Mannucci E, et al. Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis. Expert Opin Drug Saf. 2014;13(10):1327-51.

  65. Elagizi A, Köhler TS, Lavie CJ. Testosterone and Cardiovascular Health. Mayo Clin Proc. 2018;93(1):83-100. DOI: 10.1016/j.mayocp.2017.11.006

  66. Desroches B, Kohn TP, Welliver C, Pastuszak AW. Testosterone therapy in the new era of Food and Drug Administration oversight. Transl Androl Urol. 2016;5(2):207-12.

  67. Corona G, Dicuio M, Rastrelli G, Maseroli E, Lotti F, Sforza A, et al. Testosterone treatment and cardiovascular and venous thromboembolism risk: what is 'new'? J Investig Med. 2017;65:964-73.

  68. Jones TH. Testosterone and cardiovascular disease. Heart Metab. 2015;66:7-12.

  69. Rosano G, Vitale C. Testosterone in men with hypogonadism and high cardiovascular risk, Pros. Endocrine. 2015;50:320-5.

  70. Gagliano-Jucá T, Basaria S. Testosterone replacement therapy and cardiovascular risk. Nature Reviews Cardiology. 2019;16:555-74.

  71. Yeap BB, Anawalt BD. Why is understanding the relationship of testosterone to cardiovascular risk so important? Asian J Androl. 2018;20:107-8.

  72. Yeap BB. Testosterone and its metabolites: differential associations with cardiovascular and cerebrovascular events in men. Asian J Androl. 2018;20:109-14.

  73. Meyer EJ, Wittert G. Endogenous testosterone and mortality risk. Asian J Androl. 2018;20:115-9.

  74. Jones TH, Kelly DM. Randomized controlled trials - mechanistic studies of testosterone and the cardiovascular system. Asian J Androl. 2018;20:120-30.

  75. Gagliano-Juca T, Basaria S. Trials of testosterone replacement reporting cardiovascular adverse events. Asian J Androl. 2018; 20:131-7.

  76. Shores MM. Testosterone treatment and cardiovascular events in analyses of prescription databases. Asian J Androl. 2018;20: 138-44.

  77. An Q, Gu YQ. Testosterone replacement therapy: dilemmas and challenges in China and Asia. Asian J Androl. 2018;20:149-51.

  78. Holmegard HN, Nordestgaard BG, Jensen GB, Tybjærg-Hansen A, Benn M. Sex Hormones and Ischemic Stroke: A Prospective Cohort Study and Meta-Analyses. J Clin Endocrinol Metab. 2016:101:69-78.

  79. Luo S, Yeung SLA, Zhao JV, Burgess S, Schooling M. Association of genetically predicted testosterone with thromboembolism, heart failure, and myocardial infarction: mendelian randomisation study in UK Biobank. BMJ. 2019;364:l476. DOI: 10.1136/bmj.l476

  80. Pantalone KM, George J, Ji X, Kattan MW, Milinovich A, Bauman JM, et al. Testosterone replacement therapy and the risk of adverse cardiovascular outcomes and mortality. Basic Clin Andrology. 2019;29:5-13. DOI: 10.1186/s12610-019-0085-7

  81. Haider A, Yassin A, Haider KS, Doros G, Saad F, Rosano GM. Men with testosterone deficiency and a history of cardiovascular diseases benefit from long-term testosterone therapy: observational, real-life data from a registry study. Vasc Health Risk Manag. 2016 [acceso: 05/08/2019]; 12:251-61. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913536.

  82. Sharma R, Olurinde A, Gupta K, Chen G, Sharma M, Dawn B, et al. Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Eur Heart J. 2015;10:1-10.

  83. US National Institute of Health. Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE) Study. 2018 [acceso: 28/10/2019]. Disponible en: Disponible en: https://clinicaltrials.gov/ct2/show/NCT03518034

  84. Nieschlag E. Current topics in testosterone replacement of hypogonadal men. Best Pract Res Clin Endocrinol Metab. 2015;29:77-90.

  85. Dimopoulou C, EMAS Study Group. EMAS position statement: Testosterone replacement therapy in the aging male. Maturitas. 2016;84:94-9.

  86. Corona G, Sforza A, Maggi M. Testosterone Replacement Therapy: Long-Term Safety and Efficacy. World J Mens Health. 2017;35(2):65-76. DOI: 10.5534/wjmh.2017.35.2.65

  87. Shin YS, Park JK. The Optimal Indication for Testosterone Replacement Therapy in Late Onset Hypogonadism. J. Clin. Med. 2019;8(2):209-20. DOI:10.3390/jcm8020209




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