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Androgen Deprivation Therapy for Prostate Cancer: Effects on Body Composition and Metabolic Health

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Energy Balance and Prostate Cancer

Part of the book series: Energy Balance and Cancer ((EBAC,volume 14))

Abstract

Prostate cancer (PCa) is the most common malignancy diagnosed in American men. Androgen-deprivation therapy (ADT) has become the standard treatment for locally invasive, recurrent and metastatic PCa. Despite its effectiveness in lowering testosterone levels and improving survival in a subset of patients, ADT is associated with adverse effects including sexual dysfunction, vasomotor symptoms, anemia, osteoporosis and decreased quality of life. Altered body composition, resulting in reduced muscle mass and increased fat mass, is also frequently encountered in patients receiving ADT. As a result of these adverse changes in body composition, metabolic complications such as insulin resistance, diabetes, dyslipidemia and metabolic syndrome have also increased. These metabolic disturbances might be responsible for the increased cardiovascular morbidity and mortality seen in this patient population. Thus, screening, monitoring and treatment for cardiovascular risk factors (i.e. hyperglycemia, diabetes, hyperlipidemia, hypertension, obesity) in men receiving ADT might be prudent. Here we review the literature evaluating body composition changes as well as metabolic and cardiovascular complications of ADT.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.

    Google Scholar 

  2. Smith MR. Androgen deprivation therapy for prostate cancer: new concepts and concerns. Curr Opin Endocrinol Diabetes Obes. 2007;14(3):247–54.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bubley GJ, et al. Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group. J Clin Oncol. 1999;17(11):3461–7.

    Article  CAS  PubMed  Google Scholar 

  4. Messing EM, et al. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med. 1999;341(24):1781–8.

    Article  CAS  PubMed  Google Scholar 

  5. Sharifi N, Gulley JL, Dahut WL. Androgen deprivation therapy for prostate cancer. JAMA. 2005;294(2):238–44.

    Article  CAS  PubMed  Google Scholar 

  6. Shahinian VB, et al. Increasing use of gonadotropin-releasing hormone agonists for the treatment of localized prostate carcinoma. Cancer. 2005;103(8):1615–24.

    Article  CAS  PubMed  Google Scholar 

  7. Levine GN, et al. Androgen-deprivation therapy in prostate cancer and cardiovascular risk: a science advisory from the American Heart Association, American Cancer Society, and American Urological Association: endorsed by the American Society for Radiation Oncology. CA Cancer J Clin. 2010;60(3):194–201.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Labrie F, et al. Gonadotropin-releasing hormone agonists in the treatment of prostate cancer. Endocr Rev. 2005;26(3):361–79.

    Article  CAS  PubMed  Google Scholar 

  9. Connolly RM, Carducci MA, Antonarakis ES. Use of androgen deprivation therapy in prostate cancer: indications and prevalence. Asian J Androl. 2012;14(2):177–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Storer TW, Miciek R, Travison TG. Muscle function, physical performance and body composition changes in men with prostate cancer undergoing androgen deprivation therapy. Asian J Androl. 2012;14(2):204–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Basaria S. Androgen deprivation therapy, insulin resistance, and cardiovascular mortality: an inconvenient truth. J Androl. 2008;29(5):534–9.

    Article  PubMed  Google Scholar 

  12. Spitzer M, et al. Risks and benefits of testosterone therapy in older men. Nat Rev Endocrinol. 2013;9(7):414–24.

    Article  CAS  PubMed  Google Scholar 

  13. Vermeulen A, Goemaere S, Kaufman JM. Testosterone, body composition and aging. J Endocrinol Invest. 1999;22(5 Suppl):110–6.

    CAS  PubMed  Google Scholar 

  14. Basaria S, Dobs AS. Hypogonadism and androgen replacement therapy in elderly men. Am J Med. 2001;110(7):563–72.

    Article  CAS  PubMed  Google Scholar 

  15. Derby CA, et al. Body mass index, waist circumference and waist to hip ratio and change in sex steroid hormones: the Massachusetts Male Ageing Study. Clin Endocrinol (Oxf). 2006;65(1):125–31.

    Article  CAS  Google Scholar 

  16. Ding EL, et al. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2006;295(11):1288–99.

    Article  CAS  PubMed  Google Scholar 

  17. Laaksonen DE, et al. Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care. 2004;27(5):1036–41.

    Article  CAS  PubMed  Google Scholar 

  18. Wu FC, von Eckardstein A. Androgens and coronary artery disease. Endocr Rev. 2003;24(2):183–217.

    Article  CAS  PubMed  Google Scholar 

  19. Corona G, et al. Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study. Eur J Endocrinol. 2011;165(5):687–701.

    Article  CAS  PubMed  Google Scholar 

  20. Bhasin S, et al. The mechanisms of androgen effects on body composition: mesenchymal pluripotent cell as the target of androgen action. J Gerontol A Biol Sci Med Sci. 2003;58(12):M1103–10.

    Article  PubMed  Google Scholar 

  21. Lin HY, et al. Increased hepatic steatosis and insulin resistance in mice lacking hepatic androgen receptor. Hepatology. 2008;47(6):1924–35.

    Article  CAS  PubMed  Google Scholar 

  22. Nathan L, et al. Testosterone inhibits early atherogenesis by conversion to estradiol: critical role of aromatase. Proc Natl Acad Sci USA. 2001;98(6):3589–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Smith MR, et al. Changes in body composition during androgen deprivation therapy for prostate cancer. J Clin Endocrinol Metab. 2002;87(2):599–603.

    Article  CAS  PubMed  Google Scholar 

  24. Smith MR. Changes in fat and lean body mass during androgen-deprivation therapy for prostate cancer. Urology. 2004;63(4):742–5.

    Article  PubMed  Google Scholar 

  25. Basaria S, et al. Long-term effects of androgen deprivation therapy in prostate cancer patients. Clin Endocrinol (Oxf). 2002;56(6):779–86.

    Article  CAS  Google Scholar 

  26. Smith JC, et al. The effects of induced hypogonadism on arterial stiffness, body composition, and metabolic parameters in males with prostate cancer. J Clin Endocrinol. 2001;86(9):4261–7.

    Article  CAS  Google Scholar 

  27. Lee H, et al. Changes in bone mineral density and body composition during initial and long-term gonadotropin-releasing hormone agonist treatment for prostate carcinoma. Cancer. 2005;104(8):1633–7.

    Article  CAS  PubMed  Google Scholar 

  28. van Londen GJ, et al. Body composition changes during androgen deprivation therapy for prostate cancer: a 2-year prospective study. Crit Rev Oncol Hematol. 2008;68(2):172–7.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Haseen F, et al. The effect of androgen deprivation therapy on body composition in men with prostate cancer: systematic review and meta-analysis. J Cancer Surviv. 2010;4(2):128–39.

    Article  PubMed  Google Scholar 

  30. Hughes VA, et al. Longitudinal changes in body composition in older men and women: role of body weight change and physical activity. Am J Clin Nutr. 2002;76(2):473–81.

    CAS  PubMed  Google Scholar 

  31. Collins L, Basaria S. Adverse effects of androgen deprivation therapy in men with prostate cancer: a focus on metabolic and cardiovascular complications. Asian J Androl. 2012;14(2):222–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Grundy SM. Obesity, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metabol. 2004;89(6):2595–600.

    Article  CAS  Google Scholar 

  33. Muller M, et al. Endogenous sex hormones and metabolic syndrome in aging men. J Clin Endocrinol Metabol. 2005;90(5):2618–23.

    Article  CAS  Google Scholar 

  34. Haffner SM, et al. Low levels of sex hormone-binding globulin and testosterone predict the development of non-insulin-dependent diabetes mellitus in men. MRFIT Research Group. Multiple Risk Factor Intervention Trial. Am J Epidemiol. 1996;143(9):889–97.

    Article  CAS  PubMed  Google Scholar 

  35. Haffner SM, et al. Relationship of sex hormones to lipids and lipoproteins in nondiabetic men. J Clin Endocrinol Metabol. 1993;77(6):1610–5.

    CAS  Google Scholar 

  36. Pitteloud N, et al. Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men. J Clin Endocrinol Metabol. 2005;90(5):2636–41.

    Article  CAS  Google Scholar 

  37. Marin P, et al. The effects of testosterone treatment on body composition and metabolism in middle-aged obese men. Int J Obes Relat Metab Disord. 1992;16(12):991–7.

    CAS  PubMed  Google Scholar 

  38. Basaria S, et al. Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen-deprivation therapy. Cancer. 2006;106(3):581–8.

    Article  CAS  PubMed  Google Scholar 

  39. Smith MR, Lee H, Nathan DM. Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metabol. 2006;91(4):1305–8.

    Article  CAS  Google Scholar 

  40. Dockery F, et al. Testosterone suppression in men with prostate cancer leads to an increase in arterial stiffness and hyperinsulinaemia. Clin Sci (Lond). 2003;104(2):195–201.

    Article  CAS  Google Scholar 

  41. Saglam HS, et al. Fasting blood glucose and lipid profile alterations following twelve-month androgen deprivation therapy in men with prostate cancer. ScientificWorldJournal. 2012;2012:696329.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Derweesh IH, et al. Risk of new-onset diabetes mellitus and worsening glycaemic variables for established diabetes in men undergoing androgen-deprivation therapy for prostate cancer. BJU Int. 2007;100(5):1060–5.

    PubMed  Google Scholar 

  43. Keating NL, O'Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol. 2006;24(27):4448–56.

    Article  CAS  PubMed  Google Scholar 

  44. Zmuda JM, et al. Longitudinal relation between endogenous testosterone and cardiovascular disease risk factors in middle-aged men. A 13-year follow-up of former Multiple Risk Factor Intervention Trial participants. Am J Epidemiol. 1997;146(8):609–17.

    Article  CAS  PubMed  Google Scholar 

  45. Malkin CJ, et al. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab. 2004;89(7):3313–8.

    Article  CAS  PubMed  Google Scholar 

  46. Braga-Basaria M, et al. Lipoprotein profile in men with prostate cancer undergoing androgen deprivation therapy. Int J Impot Res. 2006;18(5):494–8.

    Article  CAS  PubMed  Google Scholar 

  47. Mitsuzuka K, et al. Influence of 1 year of androgen deprivation therapy on lipid and glucose metabolism and fat accumulation in Japanese patients with prostate cancer. Prostate Cancer Prostatic Dis. 2016;19(1):57–62.

    Article  CAS  PubMed  Google Scholar 

  48. Salvador C, et al. Analysis of the lipid profile and atherogenic risk during androgen deprivation therapy in prostate cancer patients. Urol Int. 2013;90(1):41–4.

    Article  CAS  PubMed  Google Scholar 

  49. Ford ES. Prevalence of the metabolic syndrome in US populations. Endocrinol Metab Clin North Am. 2004;33(2):333–50.

    Article  PubMed  Google Scholar 

  50. DeFronzo RA, Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care. 1991;14(3):173–94.

    Article  CAS  PubMed  Google Scholar 

  51. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1998;37(12):1595–607.

    Article  Google Scholar 

  52. Beltran-Sanchez H, et al. Prevalence and trends of metabolic syndrome in the adult U.S. population, 1999–2010. J Am Coll Cardiol. 2013;62(8):697–703.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Kupelian V, et al. Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in nonobese men. J Clin Endocrinol Metabol. 2006;91(3):843–50.

    Article  CAS  Google Scholar 

  54. Laaksonen DE, et al. The metabolic syndrome and smoking in relation to hypogonadism in middle-aged men: a prospective cohort study. J Clin Endocrinol Metab. 2005;90(2):712–9.

    Article  CAS  PubMed  Google Scholar 

  55. Samper Ots PM, et al. SIMBOSPROST: Prevalence of metabolic syndrome and osteoporosis in prostate cancer patients treated with radiotherapy and androgen deprivation therapy: A multicentre, cross-sectional study. Rep Pract Oncol Radiother. 2015;20(5):370–6.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Braga-Basaria M, et al. Metabolic syndrome in men with prostate cancer undergoing long-term androgen-deprivation therapy. J Clin Oncol. 2006;24(24):3979–83.

    Article  PubMed  Google Scholar 

  57. Ropero Valverde J, Planas Morin J, Salvador Lacambra C, Trilla Herrera E, Placer Santos J, et al. Prevalence of metabolic syndrome in prostate cancer patients under androgen deprivation therapy: Interim results of a case-control study. Eur Urol Suppl. 2011;10:337.

    Article  Google Scholar 

  58. Bosco C, et al. 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):e0117344.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Smith MR, O'Malley AJ, Keating NL. Gonadotrophin-releasing hormone agonists, diabetes and cardiovascular disease in men with prostate cancer: which metabolic syndrome? BJU Int. 2008;101(11):1335–6.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Bo JJ, et al. Androgen deprivation therapy through bilateral orchiectomy: increased metabolic risks. Asian J Androl. 2011;13(6):833–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Smith MR, et al. Adipocytokines, obesity, and insulin resistance during combined androgen blockade for prostate cancer. Urology. 2008;71(2):318–22.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Smith MR, et al. Metabolic changes during gonadotropin-releasing hormone agonist therapy for prostate cancer: differences from the classic metabolic syndrome. Cancer. 2008;112(10):2188–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Morote J, et al. The metabolic syndrome and its components in patients with prostate cancer on androgen deprivation therapy. J Urol. 2015;193(6):1963–9.

    Article  CAS  PubMed  Google Scholar 

  64. Rezaei MM, et al. Metabolic syndrome in patients with prostate cancer undergoing intermittent androgen-deprivation therapy. Can Urol Assoc J. 2016;10(9-10):E300–5.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Epstein MM, et al. Temporal trends in cause of death among Swedish and US men with prostate cancer. J Natl Cancer Inst. 2012;104(17):1335–42.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Satariano WA, Ragland KE, Van Den Eeden SK. Cause of death in men diagnosed with prostate carcinoma. Cancer. 1998;83(6):1180–8.

    Article  CAS  PubMed  Google Scholar 

  67. Basaria S. Cardiovascular disease associated with androgen-deprivation therapy: time to give it due respect. J Clin Oncol. 2015;33(11):1232–4.

    Article  CAS  PubMed  Google Scholar 

  68. Saigal CS, et al. Androgen deprivation therapy increases cardiovascular morbidity in men with prostate cancer. Cancer. 2007;110(7):1493–500.

    Article  CAS  PubMed  Google Scholar 

  69. D’Amico AV, et al. Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions. J Clin Oncol. 2007;25(17):2420–5.

    Article  PubMed  Google Scholar 

  70. Tsai HK, et al. Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality. J Natl Cancer Inst. 2007;99(20):1516–24.

    Article  PubMed  Google Scholar 

  71. Nanda A, et al. Hormonal therapy use for prostate cancer and mortality in men with coronary artery disease-induced congestive heart failure or myocardial infarction. JAMA. 2009;302(8):866–73.

    Article  CAS  PubMed  Google Scholar 

  72. Ziehr DR, et al. Association of androgen-deprivation therapy with excess cardiac-specific mortality in men with prostate cancer. BJU Int. 2015;116(3):358–65.

    Article  CAS  PubMed  Google Scholar 

  73. Conteduca V, et al. The cardiovascular risk of gonadotropin releasing hormone agonists in men with prostate cancer: an unresolved controversy. Crit Rev Oncol Hematol. 2013;86(1):42–51.

    Article  PubMed  Google Scholar 

  74. Nguyen PL, et al. Adverse effects of androgen deprivation therapy and strategies to mitigate them. Eur Urol. 2015;67(5):825–36.

    Article  CAS  PubMed  Google Scholar 

  75. Bhatia N, et al. Cardiovascular Effects of Androgen Deprivation Therapy for the Treatment of Prostate Cancer: ABCDE Steps to Reduce Cardiovascular Disease in Patients With Prostate Cancer. Circulation. 2016;133(5):537–41.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Gilbert SE, et al. Effects of a lifestyle intervention on endothelial function in men on long-term androgen deprivation therapy for prostate cancer. Br J Cancer. 2016;114(4):401–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Basaria S, Bhasin S. Targeting the skeletal muscle-metabolism axis in prostate-cancer therapy. N Engl J Med. 2012;367(10):965–7.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Section on Men’s Health, Aging and Metabolism, Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Ave, BLI-541, Boston, MA, 02115, USA

    Grace Huang M.D.

  2. Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Ave, BLI-541, Boston, MA, 02115, USA

    Shehzad Basaria M.D.

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  1. Grace Huang M.D.
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Correspondence to Grace Huang M.D. .

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Editors and Affiliations

  1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

    Elizabeth A. Platz

  2. Center for Science, Health and Society, Case Western Reserve University, Cleveland, Ohio, USA

    Nathan A. Berger

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Huang, G., Basaria, S. (2018). Androgen Deprivation Therapy for Prostate Cancer: Effects on Body Composition and Metabolic Health. In: Platz, E., Berger, N. (eds) Energy Balance and Prostate Cancer. Energy Balance and Cancer, vol 14. Springer, Cham. https://doi.org/10.1007/978-3-319-64940-5_7

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  • DOI: https://doi.org/10.1007/978-3-319-64940-5_7

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