Androgen deprivation therapy (ADT) in men with prostate cancer increases the risk of osteoporotic fractures, type 2 diabetes and, possibly, cardiovascular events.
There is considerable uncertainty about the risk–benefit ratio of ADT in non-palliative treatment; the benefits of ADT in treating non-metastatic prostate cancer need to be carefully weighed against the risks of ADT-induced adverse events.
Baseline assessment of bone health at the initiation of ADT should include measurement of bone mineral density (BMD) by dual energy x-ray absorptiometry and, in men with osteopaenia, a thoracolumbar spine x-ray.
General measures to prevent bone loss, including regular physical activity, as well as ensuring calcium and vitamin D sufficiency, should be instituted routinely.
All men with a previous minimal trauma fracture should receive pharmacological therapy unless contraindicated; for those who have not sustained a minimal trauma fracture, treatment is advised if the BMD T score is ≤ − 2.0, or if the 10-year risk of a major osteoporotic fracture exceeds 20%.
Men with prostate cancer who are receiving ADT should be closely monitored for weight gain and diabetes; intensive lifestyle intervention is recommended to prevent ADT-induced weight gain and insulin resistance.
Management of the metabolic sequelae of ADT includes optimal reduction of cardiovascular risk factors, with particular attention to weight, blood pressure, lipid profile, smoking cessation, and glycaemic control.
- 1. Australian Institute of Health and Welfare. Welfare. Cancer. Key facts and figures. Canberra: AIHW, 2007. http://www.aihw.gov.au/cancer/index.cfm (accessed Feb 2011).
- 2. ProstateCancer Foundation of Australia. Prostate cancer statistics. http://www.prostate.org.au/articleLive/pages/Prostate-Cancer-Statistics.html (accessed Feb 2011).
- 3. Damber JE, Aus G. Prostate cancer. Lancet 2008; 371: 1710-1721.
- 4. National Cancer Institute, United States National Institutes of Health. Surveillance, epidemiology and end results (SEER). Stat fact sheets: prostate cancer 2008. Bethesda, MD: NCI, 2008. http://seer.cancer.gov/statfacts/html/prost.html (accessed Feb 2011).
- 5. Satariano WA, Ragland KE, Van Den Eeden SK. Cause of death in men diagnosed with prostate carcinoma. Cancer 1998; 83: 1180-1188.
- 6. Lu-Yao G, Stukel TA, Yao SL. Changing patterns in competing causes of death in men with prostate cancer: a population based study. J Urol 2004; 171: 2285-2290.
- 7. Bolla M, de Reijke TM, Van Tienhoven G, et al. Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med 2009; 360: 2516-2527.
- 8. Sharifi N, Gulley JL, Dahut WL. Androgen deprivation therapy for prostate cancer. JAMA 2005; 294: 238-244.
- 9. Shahani S, Braga-Basaria M, Basaria S. Androgen deprivation therapy in prostate cancer and metabolic risk for atherosclerosis. J Clin Endocrinol Metab 2008; 93: 2042-2049.
- 10. Holmes-Walker DJ, Woo H, Gurney H, et al. Maintaining bone health in patients with prostate cancer. Med J Aust 2006; 184: 176-179. <MJA full text>
- 11. Medicare Australia. Pharmaceutical Benefits Schedule item reports. http://www.medicareaustralia.gov.au/statistics/pbs_item.shtml (accessed Nov 2009).
- 12. Leuprolide versus diethylstilbestrol for metastatic prostate cancer. The Leuprolide Study Group. N Engl J Med 1984; 311: 1281-1286.
- 13. Smith MR. Androgen deprivation therapy for prostate cancer: new concepts and concerns. Curr Opin Endocrinol Diabetes Obes 2007; 14: 247-254.
- 14. Jones G, Nguyen T, Sambrook P, et al. Progressive loss of bone in the femoral neck in elderly people: longitudinal findings from the Dubbo osteoporosis epidemiology study. BMJ 1994; 309: 691-695.
- 15. Dunstan DW, Zimmet PZ, Welborn TA, et al. The rising prevalence of diabetes and impaired glucose tolerance: the Australian Diabetes, Obesity and Lifestyle Study. Diabetes Care 2002; 25: 829-834.
- 16. Cooper C, Campion G, Melton LJ 3rd. Hip fractures in the elderly: a world-wide projection. Osteoporos Int 1992; 2: 285-289.
- 17. Center JR, Nguyen TV, Schneider D, et al. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 1999; 353: 878-882.
- 18. Ebeling PR. Osteoporosis in men. N Engl J Med 2008; 358: 1474-1482.
- 19. Greenspan SL. Approach to the prostate cancer patient with bone disease. J Clin Endocrinol Metab 2008; 93: 2-7.
- 20. Higano CS. Androgen-deprivation-therapy-induced fractures in men with nonmetastatic prostate cancer: what do we really know? Nat Clin Pract Urol 2008; 5: 24-34.
- 21. Panju AH, Breunis H, Cheung AM, et al. Management of decreased bone mineral density in men starting androgen-deprivation therapy for prostate cancer. BJU Int 2009; 103: 753-757.
- 22. Wadhwa VK, Weston R, Mistry R, Parr NJ. Long-term changes in bone mineral density and predicted fracture risk in patients receiving androgen-deprivation therapy for prostate cancer, with stratification of treatment based on presenting values. BJU Int 2009; 104: 800-805.
- 23. Greenspan SL, Coates P, Sereika SM, et al. Bone loss after initiation of androgen deprivation therapy in patients with prostate cancer. J Clin Endocrinol Metab 2005; 90: 6410-6417.
- 24. Diamond TH, Higano CS, Smith MR, et al. Osteoporosis in men with prostate carcinoma receiving androgen-deprivation therapy: recommendations for diagnosis and therapies. Cancer 2004; 100: 892-899.
- 25. Hamilton EJ, Ghasem-Zadeh A, Gianatti E, et al. Structural decay of bone microarchitecture in men with prostate cancer treated with androgen deprivation therapy. J Clin Endocrinol Metab 2010; 95: E456-E463.
- 26. Morote J, Orsola A, Abascal JM, et al. Bone mineral density changes in patients with prostate cancer during the first 2 years of androgen suppression. J Urol 2006; 175: 1679-1683; discussion 1683.
- 27. Morote J, Morin JP, Orsola A, et al. Prevalence of osteoporosis during long-term androgen deprivation therapy in patients with prostate cancer. Urology 2007; 69: 500-504.
- 28. Smith MR, Lee WC, Brandman J, et al. Gonadotropin-releasing hormone agonists and fracture risk: a claims-based cohort study of men with nonmetastatic prostate cancer. J Clin Oncol 2005; 23: 7897-7903.
- 29. Smith MR, Boyce SP, Moyneur E, et al. Risk of clinical fractures after gonadotropin-releasing hormone agonist therapy for prostate cancer. J Urol 2006; 175: 136-139; discussion 139.
- 30. Shahinian VB, Kuo YF, Freeman JL, Goodwin, JS. Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med 2005; 352: 154-164.
- 31. Abrahamsen B, Nielsen MF, Eskildsen P, et al. Fracture risk in Danish men with prostate cancer: a nationwide register study. BJU Int 2007; 100: 749-754.
- 32. Oefelein MG, Ricchuiti V, Conrad W, et al. Skeletal fracture associated with androgen suppression induced osteoporosis: the clinical incidence and risk factors for patients with prostate cancer. J Urol 2001; 166: 1724-1728.
- 33. Taylor LG, Canfield SE, Du XL. Review of major adverse effects of androgen-deprivation therapy in men with prostate cancer. Cancer 2009; 115: 2388-2399.
- 34. Galvao DA, Nosaka K, Taaffe DR, et al. Resistance training and reduction of treatment side effects in prostate cancer patients. Med Sci Sports Exerc 2006; 38: 2045-2052.
- 35. Segal RJ, Reid RD, Courneya KS, et al. Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. J Clin Oncol 2003; 21: 1653-1659.
- 36. Giovannucci E, Rimm EB, Wolk A, et al. Calcium and fructose intake in relation to risk of prostate cancer. Cancer Res 1998; 58: 442-447.
- 37. Diamond TH, Bucci J, Kersley JH, et al. Osteoporosis and spinal fractures in men with prostate cancer: risk factors and effects of androgen deprivation therapy. J Urol 2004; 172: 529-532.
- 38. Smith MR, McGovern FJ, Zietman AL, et al. Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Engl J Med 2001; 345: 948-955.
- 39. Diamond TH, Winters J, Smith A, et al. The antiosteoporotic efficacy of intravenous pamidronate in men with prostate carcinoma receiving combined androgen blockade: a double blind, randomized, placebo-controlled crossover study. Cancer 2001; 92: 1444-1450.
- 40. Michaelson MD, Kaufman DS, Lee H, et al. Randomized controlled trial of annual zoledronic acid to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer. J Clin Oncol 2007; 25: 1038-1042.
- 41. Smith MR, Eastham J, Gleason DM, et al. Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol 2003; 169: 2008-2012.
- 42. Satoh T, Kimura M, Matsumoto K, et al. Single infusion of zoledronic acid to prevent androgen deprivation therapy-induced bone loss in men with hormone-naive prostate carcinoma. Cancer 2009; 115: 3468-3474.
- 43. Ryan CW, Huo D, Bylow K, et al. Suppression of bone density loss and bone turnover in patients with hormone-sensitive prostate cancer and receiving zoledronic acid. BJU Int 2007; 100: 70-75.
- 44. Greenspan SL, Nelson JB, Trump DL, Resnick NM. Effect of once-weekly oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer: a randomized trial. Ann Intern Med 2007; 146: 416-424.
- 45. Planas J, Trilla E, Raventos C, et al. Alendronate decreases the fracture risk in patients with prostate cancer on androgen-deprivation therapy and with severe osteopenia or osteoporosis. BJU Int 2009; 104: 1637-1640.
- 46. Ishizaka K, Machida T, Kobayashi S, et al. Preventive effect of risedronate on bone loss in men receiving androgen-deprivation therapy for prostate cancer. Int J Urol 2007; 14: 1071-1075.
- 47. Izumi K, Mizokami A, Sugimoto K, et al. Risedronate recovers bone loss in patients with prostate cancer undergoing androgen-deprivation therapy. Urology 2009; 73: 1342-1346.
- 48. Smith MR, Egerdie B, Hernandez Toriz N, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 2009; 361: 745-755.
- 49. Smith MR, Fallon MA, Lee H, Finkelstein JS. Raloxifene to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: a randomized controlled trial. J Clin Endocrinol Metab 2004; 89: 3841-3846.
- 50. Smith MR, Malkowicz SB, Chu F, et al. Toremifene increases bone mineral density in men receiving androgen deprivation therapy for prostate cancer: interim analysis of a multicenter phase 3 clinical study. J Urol 2008; 179: 152-155.
- 51. Tanvetyanon T. Physician practices of bone density testing and drug prescribing to prevent or treat osteoporosis during androgen deprivation therapy. Cancer 2005; 103: 237-241.
- 52. Wilcox A, Carnes ML, Moon TD, et al. Androgen deprivation in veterans with prostate cancer: implications for skeletal health. Ann Pharmacother 2006; 40: 2107-2114.
- 53. Sanders KM, Nowson CA, Kotowicz MA, et al. Calcium and bone health: position statement for the Australian and New Zealand Bone and Mineral Society, Osteoporosis Australia and the Endocrine Society of Australia. Med J Aust 2009; 190: 316-320. <MJA full text>
- 54. Reid DM, Doughty J, Eastell R, et al. Guidance for the management of breast cancer treatment-induced bone loss: a consensus position statement from a UK Expert Group. Cancer Treat Rev 2008; 34 Suppl 1: S3-S18.
- 55. Kanis JA, Stevenson M, McCloskey EV, et al. Glucocorticoid-induced osteoporosis: a systematic review and cost-utility analysis. Health Technol Assess 2007; 11, iii-iv, ix-xi: 1-231.
- 56. Grossmann M, Thomas MC, Panagiotopoulos S, et al. Low testosterone levels are common and associated with insulin resistance in men with diabetes. J Clin Endocrinol Metab 2008; 93: 1834-1840.
- 57. Allan CA, McLachlan RI. Age-related changes in testosterone and the role of replacement therapy in older men. Clin Endocrinol (Oxf) 2004; 60: 653-670.
- 58. Basaria S, Lieb J 2nd, Tang AM, et al. Long-term effects of androgen deprivation therapy in prostate cancer patients. Clin Endocrinol (Oxf) 2002; 56: 779-786.
- 59. Smith MR, Finkelstein JS, McGovern FJ, et al. Changes in body composition during androgen deprivation therapy for prostate cancer. J Clin Endocrinol Metab 2002; 87: 599-603.
- 60. Smith MR, Lee H, Nathan DM. Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab 2006; 91: 1305-1308.
- 61. Hamilton EJ, Gianatti E, Strauss BJ, et al. Increase in visceral and subcutaneous abdominal fat in men with prostate cancer treated with androgen deprivation therapy. Clin Endocrinol (Oxf) 2011; 74: 377-383.
- 62. Zamboni M, Mazzali G, Fantin F, et al. Sarcopenic obesity: a new category of obesity in the elderly. Nutr Metab Cardiovasc Dis 2008; 18: 388-395.
- 63. Shepherd PR, Kahn BB. Glucose transporters and insulin action implications for insulin resistance and diabetes mellitus. N Engl J Med 1999; 341: 248-257.
- 64. Smith JC, Bennett S, Evans LM, et al. The effects of induced hypogonadism on arterial stiffness, body composition, and metabolic parameters in males with prostate cancer. J Clin Endocrinol Metab 2001; 86: 4261-4267.
- 65. Dockery F, Bulpitt CJ, Agarwal S, et al. Testosterone suppression in men with prostate cancer leads to an increase in arterial stiffness and hyperinsulinaemia. Clin Sci (Lond) 2003; 104: 195-201.
- 66. Keating NL, O’Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol 2006; 24: 4448-4456.
- 67. Haidar A, Yassin A, Saad F, Shabsigh R. Effects of androgen deprivation on glycaemic control and on cardiovascular biochemical risk factors in men with advanced prostate cancer with diabetes. Aging Male 2007; 10: 189-196.
- 68. Despres JP, Lamarche B, Mauriege P, et al. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 1996; 334: 952-957.
- 69. Van Hemelrick M, Garmo H, Bratt H, et al. Increased cardiovascular morbidity and mortality following endocrine treatment for prostate cancer: an analysis in 30 642 men in PCBaSe Sweden [abstract 1Ba]. Eur J CancerSupp 2009; 7: 1.
- 70. Saigal CS, Gore JL, Krupski TL, et al. Androgen deprivation therapy increases cardiovascular morbidity in men with prostate cancer. Cancer 2007; 110: 1493-1500.
- 71. D’Amico AV, Denham JW, Crook J, et al. Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions. J Clin Oncol 2007; 25: 2420-2425.
- 72. Twigg SM, Kamp MC, Davis TM, et al. Prediabetes: a position statement from the Australian Diabetes Society and Australian Diabetes Educators Association. Med J Aust 2007; 186: 461-465. <MJA full text>
- 73. Lipid management guidelines —2001. National Heart Foundation of Australia, The Cardiac Society of Australia and New Zealand. Med J Aust 2001; 175 (9 Suppl): S57-S88.
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