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The use of exercise interventions to overcome adverse effects of androgen deprivation therapy

Nature Reviews Urology volume 13, pages 353–364 (2016)Cite this article

Subjects

Key Points

  • Androgen deprivation therapy (ADT) adversely affects lean body mass, fat mass and bone mineral density, resulting in an increased risk of diabetes mellitus, bone fracture and possibly cardiovascular disease

  • Exercise can mitigate ADT-induced changes in body composition and physical functioning, but trials that investigate its effect on the risks of diabetes mellitus, bone fracture and cardiovascular disease are still warranted

  • Exercise can mitigate fatigue, improve disease-specific quality of life (although probably more difficult to achieve) and might also have a positive effect on sexual functioning in men with prostate cancer receiving ADT

  • The safety and effects of physical activity in men with prostate cancer and bone metastases require further investigation

Abstract

Androgen deprivation therapy (ADT) induces severe hypogonadism and is associated with several adverse effects that negatively affect health and quality of life in patients with prostate cancer. ADT changes body composition characterized by an increase in fat mass and a reduction in muscle mass and strength. Insulin sensitivity is also diminished and population-based studies indicate an increased risk of diabetes mellitus and cardiovascular disease in men receiving ADT. Particularly the first 6 months of treatment seem to hold an additional risk of new cardiovascular events for patients with already existing cardiovascular disease. In this initial phase of ADT, metabolic changes are also most prominent. In addition, ADT increases the rate of bone loss and fracture risk. Currently available evidence supports the use of exercise interventions to improve physical function and mitigate ADT-induced fatigue. Some studies also indicate that exercise might moderate ADT-related changes in body composition. However, beneficial effects of exercise interventions on other ADT-related conditions have not been conclusively proven. Trials investigating the effects of ADT on fracture risk and development of diabetes mellitus and cardiovascular disease are still warranted. Furthermore, studies investigating safety and effects of physical activity in men with bone metastases are lacking.

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References

  1. Pagliarulo, V. et al. Contemporary role of androgen deprivation therapy for prostate cancer. Eur. Urol. 61, 11–25 (2012).

    Article  CAS  PubMed  Google Scholar 

  2. Smith, M. R. et al. Sarcopenia during androgen-deprivation therapy for prostate cancer. J. Clin. Oncol. 30, 3271–3276 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Zitzmann, M. Testosterone deficiency, insulin resistance and the metabolic syndrome. Nat. Rev. Endocrinol. 5, 673–681 (2009).

    Article  CAS  PubMed  Google Scholar 

  4. Keating, N. L., O'Malley, A. J. & Smith, M. R. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J. Clin. Oncol. 24, 4448–4456 (2006).

    Article  CAS  Google Scholar 

  5. O'Farrell, S. et al. Risk and timing of cardiovascular disease after androgen-deprivation therapy in men with prostate cancer. J. Clin. Oncol. 33, 1243–1251 (2015).

    Article  CAS  PubMed  Google Scholar 

  6. Jespersen, C. G., Nørgaard, M. & Borre, M. Androgen-deprivation therapy in treatment of prostate cancer and risk of myocardial infarction and stroke: a nationwide Danish population-based cohort study. Eur. Urol. 65, 704–709 (2014).

    Article  CAS  PubMed  Google Scholar 

  7. Alibhai, S. M. H. et al. Changes in bone mineral density in men starting androgen deprivation therapy and the protective role of vitamin D. Osteoporos. Int. 24, 2571–2579 (2013).

    Article  CAS  PubMed  Google Scholar 

  8. Cormie, P., Newton, R. U. & Taaffe, D. R., Spry, N. & Galvão, D. A. Exercise therapy for sexual dysfunction after prostate cancer. Nat. Rev. Urol. 10, 731–736 (2013).

    Article  CAS  PubMed  Google Scholar 

  9. Hussain, M. et al. Intermittent versus continuous androgen deprivation in prostate cancer. N. Engl. J. Med. 368, 1314–1325 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Alberga, A. S. et al. Age and androgen-deprivation therapy on exercise outcomes in men with prostate cancer. Support. Care Cancer 20, 971–981 (2012).

    Article  PubMed  Google Scholar 

  11. Bourke, L. et al. Lifestyle intervention in men with advanced prostate cancer receiving androgen suppression therapy: a feasibility study. Cancer Epidemiol. Biomarkers Prev. 20, 647–657 (2011).

    Article  PubMed  Google Scholar 

  12. Bourke, L. et al. Lifestyle changes for improving disease-specific quality of life in sedentary men on long-term androgen-deprivation therapy for advanced prostate cancer: a randomised controlled trial. Eur. Urol. 65, 865–872 (2014).

    Article  PubMed  Google Scholar 

  13. Cormie, P. et al. Safety and efficacy of resistance exercise in prostate cancer patients with bone metastases. Prostate Cancer Prostatic Dis. 16, 328–335 (2013).

    Article  CAS  PubMed  Google Scholar 

  14. Cormie, P. et al. Can supervised exercise prevent treatment toxicity in patients with prostate cancer initiating androgen-deprivation therapy: a randomised controlled trial. BJU Int. 115, 256–266 (2015).

    Article  PubMed  Google Scholar 

  15. Culos-Reed, S. N., Robinson, J. L., Lau, H., O'Connor, K. & Keats, M. R. Benefits of a physical activity intervention for men with prostate cancer. J. Sport Exerc. Psychol. 29, 118–127 (2007).

    Article  PubMed  Google Scholar 

  16. Culos-Reed, S. N. et al. Physical activity for men receiving androgen deprivation therapy for prostate cancer: benefits from a 16-week intervention. Support. Care Cancer 18, 591–599 (2010).

    Article  PubMed  Google Scholar 

  17. Hanson, E. D. et al. Strength training induces muscle hypertrophy and functional gains in black prostate cancer patients despite androgen deprivation therapy. J. Gerontol. A Biol. Sci. Med. Sci. 68, 490–498 (2013).

    Article  CAS  PubMed  Google Scholar 

  18. Galvão, D. A. et al. Resistance training and reduction of treatment side effects in prostate cancer. Med. Sci. Sports Exerc. 38, 2045–2052 (2006).

    Article  PubMed  Google Scholar 

  19. Galvão, D. A. et al. Endocrine and immune responses to resistance training in prostate cancer patients. Prostate Cancer Prostatic Dis. 11, 160–165 (2008).

    Article  CAS  PubMed  Google Scholar 

  20. Galvão, D. A., Taaffe, D. R., Spry, N., Joseph, D. & Newton, R. U. Combined resistance and aerobic exercise program reverses muscle loss in men undergoing androgen suppression therapy for prostate cancer without bone metastases: a randomized controlled trial. J. Clin. Oncol. 28, 340–347 (2010).

    Article  CAS  PubMed  Google Scholar 

  21. Galvão, D. A., Taaffe, D. R., Spry, N., Joseph, D. & Newton, R. U. Acute versus chronic exposure to androgen suppression for prostate cancer: impact on the exercise response. J. Urol. 186, 1291–1297 (2011).

    Article  CAS  PubMed  Google Scholar 

  22. Galvão, D. A. et al. A multicentre year-long randomised controlled trial of exercise training targeting physical functioning in men with prostate cancer previously treated with androgen suppression and radiation from TROG 03.04 RADAR. Eur. Urol. 65, 856–864 (2014).

    Article  PubMed  Google Scholar 

  23. Mina, D. S. et al. A randomized trial of aerobic versus resistance exercise in prostate cancer survivors. J. Aging Phys. Act. 21, 455–478 (2013).

    Article  Google Scholar 

  24. O'Neill, R. F., Haseen, F., Murray, L. J., O'Sullivan, J. M. & Cantwell, M. M. A randomised controlled trial to evaluate the efficacy of a 6-month dietary and physical activity intervention for patients receiving androgen deprivation therapy for prostate cancer. J. Cancer Surviv. 9, 431–440 (2015).

    Article  PubMed  Google Scholar 

  25. Segal, R. J. et al. Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. J. Clin. Oncol. 21, 1653–1659 (2003).

    Article  PubMed  Google Scholar 

  26. Segal, R. J. et al. Randomized controlled trial of resistance or aerobic exercise in men receiving radiation therapy for prostate cancer. J. Clin. Oncol. 27, 344–351 (2009).

    Article  PubMed  Google Scholar 

  27. Winters-Stone, K. M. et al. Skeletal response to resistance and impact training in prostate cancer survivors. Med. Sci. Sports Exerc. 46, 1482–1488 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hvid, T. et al. Endurance training improves insulin sensitivity and body composition in prostate cancer patients treated with androgen deprivation therapy. Endocr. Relat. Cancer 20, 621–632 (2013).

    Article  CAS  PubMed  Google Scholar 

  29. Cormie, P. et al. Improving sexual health in men with prostate cancer: randomised controlled trial of exercise and psychosexual therapies. BMC Cancer 14, 199 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Stenholm, S. et al. Sarcopenic obesity: definition, cause and consequences. Curr. Opin. Clin. Nutr. Metab. Care 11, 693–700 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Fielding, R. A. et al. Sarcopenia: an undiagnosed condition in older adults. current consensus definition: prevalence, etiology, and consequences. J. Am. Med. Dir. Assoc. 12, 249–256 (2011).

    Article  PubMed  Google Scholar 

  32. Isidori, A. M. et al. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. International Working Group on Sarcopenia. Clin. Endocrinol. (Oxf.) 63, 280–293 (2005).

    Article  CAS  Google Scholar 

  33. Finkelstein, J. S. et al. Gonadal steroids and body composition, strength, and sexual function in men. N. Engl. J. Med. 369, 1011–1022 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Galvão, D. A. et al. Changes in muscle, fat and bone mass after 36 weeks of maximal androgen blockade for prostate cancer. BJU Int. 102, 44–47 (2008).

    Article  PubMed  Google Scholar 

  35. Smith, M. R. et al. Changes in body composition during androgen deprivation therapy for prostate cancer. J. Clin. Endocrinol. Metab. 87, 599–603 (2002).

    Article  CAS  PubMed  Google Scholar 

  36. Smith, M. R. Changes in fat and lean body mass during androgen-deprivation therapy for prostate cancer. Urology 63, 742–745 (2004).

    Article  PubMed  Google Scholar 

  37. Lee, H., McGovern, K., Finkelstein, J. S. & Smith, M. R. Changes in bone mineral density and body composition during initial and long-term gonadotropin-releasing hormone agonist treatment for prostate carcinoma. Cancer 104, 1633–1637 (2005).

    Article  CAS  PubMed  Google Scholar 

  38. Van Londen, G. J., Levy, M. E., Perera, S., Nelson, J. B. & Greenspan, S. L. Body composition changes during androgen deprivation therapy for prostate cancer: a 2-year prospective study. Crit. Rev. Oncol. Hematol. 68, 172–177 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Keating, N. L., O'Malley, A. J., Freedland, S. J. & Smith, M. R. Diabetes and cardiovascular disease during androgen deprivation therapy: observational study of veterans with prostate cancer. J. Natl Cancer Inst. 102, 39–46 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Alibhai, S. M. H. et al. Impact of androgen deprivation therapy on cardiovascular disease and diabetes. J. Clin. Oncol. 27, 3452–3458 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Keating, N. L., Liu, P.-H., O'Malley, A. J., Freedland, S. J. & Smith, M. R. Androgen-deprivation therapy and diabetes control among diabetic men with prostate cancer. Eur. Urol. 65, 816–824 (2014).

    Article  CAS  PubMed  Google Scholar 

  42. Smith, J. C. et al. The effects of induced hypogonadism on arterial stiffness, body composition, and metabolic parameters in males with prostate cancer. J. Clin. Endocrinol. Metab. 86, 4261–4267 (2001).

    Article  CAS  PubMed  Google Scholar 

  43. Nguyen, P. L. et al. Androgen deprivation therapy reversibly increases endothelium-dependent vasodilation in men with prostate cancer. J. Am. Heart Assoc. 4, e001914–e001914 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Smith, M. R., Lee, H. & Nathan, D. M. Insulin sensitivity during combined androgen blockade for prostate cancer. J. Clin. Endocrinol. Metab. 91, 1305–1308 (2006).

    Article  CAS  PubMed  Google Scholar 

  45. Smith, M. R., Lee, H., Fallon, M. A. & Nathan, D. M. Adipocytokines, obesity, and insulin resistance during combined androgen blockade for prostate cancer. Urology 71, 318–322 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Yu, I.-C., Lin, H.-Y., Sparks, J. D., Yeh, S. & Chang, C. Androgen receptor roles in insulin resistance and obesity in males: the linkage of androgen-deprivation therapy to metabolic syndrome. Diabetes 63, 3180–3188 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Gillies, C. L. et al. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. BMJ 334, 299 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Elliott, L. & Cifu, A. S. Healthy lifestyle counseling in persons with cardiovascular risk factors. JAMA 314, 398–399 (2015).

    Article  CAS  PubMed  Google Scholar 

  49. Tsai, H. K., D'Amico, A. V., Sadetsky, N., Chen, M.-H. & Carroll, P. R. Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality. J. Natl Cancer Inst. 99, 1516–1524 (2007).

    Article  PubMed  Google Scholar 

  50. Saigal, C. S. et al. Androgen deprivation therapy increases cardiovascular morbidity in men with prostate cancer. Cancer 110, 1493–1500 (2007).

    Article  CAS  PubMed  Google Scholar 

  51. Albertsen, P. C. et al. Cardiovascular morbidity associated with gonadotropin releasing hormone agonists and an antagonist. Eur. Urol. 65, 565–573 (2014).

    Article  CAS  PubMed  Google Scholar 

  52. Nguyen, P. L. et al. Coronary revascularization and mortality in men with congestive heart failure or prior myocardial infarction who receive androgen deprivation. Cancer 117, 406–413 (2011).

    Article  PubMed  Google Scholar 

  53. Nguyen, P. L. et al. Influence of androgen deprivation therapy on all-cause mortality in men with high-risk prostate cancer and a history of congestive heart failure or myocardial infarction. Int. J. Radiat. Oncol. 82, 1411–1416 (2012).

    Article  Google Scholar 

  54. Malkin, C. Testosterone as a protective factor against atherosclerosis — immunomodulation and influence upon plaque development and stability. J. Endocrinol. 178, 373–380 (2003).

    Article  CAS  PubMed  Google Scholar 

  55. Nguyen, P. et al. Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. JAMA 306, 2359–2366 (2011).

    Article  CAS  PubMed  Google Scholar 

  56. Dong, F., Skinner, D. C., John Wu, T. & Ren, J. The heart: a novel gonadotrophin-releasing hormone target. J. Neuroendocrinol. 23, 456–463 (2011).

    Article  CAS  PubMed  Google Scholar 

  57. Hu, J. C. et al. Androgen-deprivation therapy for nonmetastatic prostate cancer is associated with an increased risk of peripheral arterial disease and venous thromboembolism. Eur. Urol. 61, 1119–1128 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Azoulay, L. et al. Androgen-deprivation therapy and the risk of stroke in patients with prostate cancer. Eur. Urol. 60, 1244–1250 (2011).

    Article  CAS  PubMed  Google Scholar 

  59. Punnen, S., Cooperberg, M. R., Sadetsky, N. & Carroll, P. R. Androgen deprivation therapy and cardiovascular risk. J. Clin. Oncol. 29, 3510–3516 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Alberti, K. G. et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120, 1640–1645 (2009).

    Article  CAS  PubMed  Google Scholar 

  61. Bosco, C., Crawley, D., Adolfsson, J., Rudman, S. & Van Hemelrijck, M. Quantifying the evidence for the risk of metabolic syndrome and its components following androgen deprivation therapy for prostate cancer: a meta-analysis. PLoS ONE 10, e0117344 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Morote, J. et al. The metabolic syndrome and its components in patients with prostate cancer on androgen deprivation therapy. J. Urol. 193, 1963–1969 (2015).

    Article  CAS  PubMed  Google Scholar 

  63. Smith, M. R. et al. Metabolic changes during gonadotropin-releasing hormone agonist therapy for prostate cancer. Cancer 112, 2188–2194 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Eri, L. M., Urdal, P. & Bechensteen, A. G. Effects of the luteinizing hormone-releasing hormone agonist leuprolide on lipoproteins, fibrinogen and plasminogen activator inhibitor in patients with benign prostatic hyperplasia. J. Urol. 154, 100–104 (1995).

    Article  CAS  PubMed  Google Scholar 

  65. Salvador, C. et al. Analysis of the lipid profile and atherogenic risk during androgen deprivation therapy in prostate cancer patients. Urol. Int. 90, 41–44 (2013).

    Article  CAS  PubMed  Google Scholar 

  66. Fox, C. S. et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation 116, 39–48 (2007).

    Article  PubMed  Google Scholar 

  67. Saylor, P. J. & Smith, M. R. Metabolic complications of androgen deprivation therapy for prostate cancer. J. Urol. 189 (Suppl. 1), S34–S44 (2013).

    CAS  PubMed  Google Scholar 

  68. Vanderschueren, D. et al. Sex steroid actions in male bone. Endocr. Rev. 35, 906–960 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Wadhwa, V. K., Weston, R., Mistry, R. & Parr, N. J. 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. 104, 800–805 (2009).

    Article  CAS  PubMed  Google Scholar 

  70. Greenspan, S. L. et al. Bone loss after initiation of androgen deprivation therapy in patients with prostate cancer. J. Clin. Endocrinol. Metab. 90, 6410–6417 (2005).

    Article  CAS  PubMed  Google Scholar 

  71. Alibhai, S. M. et al. Fracture types and risk factors in men with prostate cancer on androgen deprivation therapy: a matched cohort study of 19,079 men. J. Urol. 184, 918–924 (2010).

    Article  PubMed  Google Scholar 

  72. Melton, L. J. et al. Fracture risk in men with prostate cancer: a population-based study. J. Bone Miner. Res. 26, 1808–1815 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Abrahamsen, B. et al. Fracture risk in Danish men with prostate cancer: a nationwide register study. BJU Int. 100, 749–754 (2007).

    Article  PubMed  Google Scholar 

  74. Thorstenson, A. et al. Incidence of fractures causing hospitalisation in prostate cancer patients: results from the population-based PCBaSe Sweden. Eur. J. Cancer 48, 1672–1681 (2012).

    Article  PubMed  Google Scholar 

  75. Shahinian, V. B., Kuo, Y.-F., Freeman, J. L. & Goodwin, J. S. Risk of fracture after androgen deprivation for prostate cancer. N. Engl. J. Med. 352, 154–164 (2005).

    Article  CAS  PubMed  Google Scholar 

  76. Hussain, S. A., Weston, R., Stephenson, R. N., George, E. & Parr, N. J. Immediate dual energy X-ray absorptiometry reveals a high incidence of osteoporosis in patients with advanced prostate cancer before hormonal manipulation. BJU Int. 92, 690–694 (2003).

    Article  CAS  PubMed  Google Scholar 

  77. Lassemillante, A.-C., Doi, S. A., Hooper, J. D., Prins, J. B. & Wright, O. R. Prevalence of osteoporosis in prostate cancer survivors: a meta-analysis. Endocrine 45, 370–381 (2014).

    Article  CAS  PubMed  Google Scholar 

  78. Roodman, G. D. Mechanisms of bone metastasis. N. Engl. J. Med. 350, 1655–1664 (2004).

    Article  CAS  PubMed  Google Scholar 

  79. Hofbauer, L. C., Rachner, T. D., Coleman, R. E. & Jakob, F. Endocrine aspects of bone metastases. Lancet Diabetes Endocrinol. 2, 500–512 (2014).

    Article  CAS  PubMed  Google Scholar 

  80. Todenhöfer, T., Stenzl, A., Hofbauer, L. C. & Rachner, T. D. Targeting bone metabolism in patients with advanced prostate cancer: current options and controversies. Int. J. Endocrinol. 2015, 1–9 (2015).

    Article  CAS  Google Scholar 

  81. Saylor, P. J. et al. Factors associated with vertebral fractures in men treated with androgen deprivation therapy for prostate cancer. J. Urol. 186, 482–486 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. El-Khoury, F., Cassou, B., Charles, M. A. & Dargent-Molina, P. The effect of fall prevention exercise programmes on fall induced injuries in community dwelling older adults: systematic review and meta-analysis of randomised controlled trials. BMJ 347, f6234 (2013).

    PubMed  PubMed Central  Google Scholar 

  83. Wu, F. C. W. et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N. Engl. J. Med. 363, 123–135 (2010).

    Article  CAS  PubMed  Google Scholar 

  84. Ng, E. et al. The influence of testosterone suppression and recovery on sexual function in men with prostate cancer: observations from a prospective study in men undergoing intermittent androgen suppression. J. Urol. 187, 2162–2167 (2012).

    Article  CAS  PubMed  Google Scholar 

  85. Rousseau, L., Dupont, A., Labrie, F. & Couture, M. Sexuality changes in prostate cancer patients receiving antihormonal therapy combining the antiandrogen flutamide with medical (LHRH agonist) or surgical castration. Arch. Sex. Behav. 17, 87–98 (1988).

    Article  CAS  PubMed  Google Scholar 

  86. Potosky, A. L. et al. Quality-of-life outcomes after primary androgen deprivation therapy: results from the Prostate Cancer Outcomes Study. J. Clin. Oncol. 19, 3750–3757 (2001).

    Article  CAS  PubMed  Google Scholar 

  87. Traish, A. M. et al. Effects of medical or surgical castration on erectile function in an animal model. J. Androl. 24, 381–387 (2003).

    Article  PubMed  Google Scholar 

  88. Baba, K. et al. Effect of testosterone on the number of NADPH diaphorase-stained nerve fibers in the rat corpus cavernosum and dorsal nerve. Urology 56, 533–538 (2000).

    Article  CAS  PubMed  Google Scholar 

  89. Giuliano, F., Rampint, O., Schirar, A., Jardin, A. & Rousseau, J.-P. Autonomie control of penile erection: modulation by testosterone in the rat. J. Neuroendocrinol. 5, 677–683 (1993).

    Article  CAS  PubMed  Google Scholar 

  90. Zhang, X., Melman, A. & DiSanto, M. E. Update on corpus cavernosum smooth muscle contractile pathways in erectile function: a role for testosterone? J. Sex. Med. 8, 1865–1879 (2011).

    Article  CAS  PubMed  Google Scholar 

  91. Higano, C. S. Sexuality and intimacy after definitive treatment and subsequent androgen deprivation therapy for prostate cancer. J. Clin. Oncol. 30, 3720–3725 (2012).

    Article  PubMed  Google Scholar 

  92. Benedict, C. et al. Sexual bother in men with advanced prostate cancer undergoing androgen deprivation therapy. J. Sex. Med. 11, 2571–2580 (2014).

    Article  PubMed  Google Scholar 

  93. Reese, J. B. Coping with sexual concerns after cancer. Curr. Opin. Oncol. 23, 313–321 (2011).

    Article  PubMed  Google Scholar 

  94. DiBlasio, C. J. et al. Patterns of sexual and erectile dysfunction and response to treatment in patients receiving androgen deprivation therapy for prostate cancer. BJU Int. 102, 39–43 (2008).

    Article  PubMed  Google Scholar 

  95. Elliott, S., Latini, D. M., Walker, L. M., Wassersug, R. & Robinson, J. W. Androgen deprivation therapy for prostate cancer: recommendations to improve patient and partner quality of life. J. Sex. Med. 7, 2996–3010 (2010).

    Article  CAS  PubMed  Google Scholar 

  96. Miles, C. L. et al. Interventions for sexual dysfunction following treatments for cancer. Cochrane Database Syst. Rev. 4, CD005540 (2007).

    Google Scholar 

  97. Sadovsky, R. et al. Cancer and sexual problems. J. Sex. Med. 7, 349–373 (2010).

    Article  PubMed  Google Scholar 

  98. Walker, L. M., Wassersug, R. J. & Robinson, J. W. Psychosocial perspectives on sexual recovery after prostate cancer treatment. Nat. Rev. Urol. 12, 167–176 (2015).

    Article  PubMed  Google Scholar 

  99. Cormie, P. et al. Exercise maintains sexual activity in men undergoing androgen suppression for prostate cancer: a randomized controlled trial. Prostate Cancer Prostatic Dis. 16, 170–175 (2013).

    Article  CAS  PubMed  Google Scholar 

  100. Hamilton, K., Chambers, S. K., Legg, M., Oliffe, J. L. & Cormie, P. Sexuality and exercise in men undergoing androgen deprivation therapy for prostate cancer. Support. Care Cancer 23, 133–142 (2015).

    Article  CAS  PubMed  Google Scholar 

  101. The Medical Research Council Prostate Cancer Working Party Investigators Group. Immediate versus deferred treatment for advanced prostatic cancer: initial results of the Medical Research Council Trial. Br. J. Urol. 79, 235–246 (1997).

  102. Casey, R. G., Corcoran, N. M. & Larry Goldenberg, S. Quality of life issues in men undergoing androgen deprivation therapy: a review. Asian J. Androl. 14, 226–231 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Herr, H. W. & O'Sullivan, M. Quality of life of asymptomatic men with nonmetastatic prostate cancer on androgen deprivation therapy. J. Urol. 163, 1743–1746 (2000).

    Article  CAS  PubMed  Google Scholar 

  104. Stone, P., Hardy, J., Huddart, R., A'Hern, R. & Richards, M. Fatigue in patients with prostate cancer receiving hormone therapy. Eur. J. Cancer 36, 1134–1141 (2000).

    Article  CAS  PubMed  Google Scholar 

  105. Langston, B., Armes, J., Levy, A., Tidey, E. & Ream, E. The prevalence and severity of fatigue in men with prostate cancer: a systematic review of the literature. Support. Care Cancer 21, 1761–1771 (2013).

    Article  PubMed  Google Scholar 

  106. McGinty, H. L. et al. Cognitive functioning in men receiving androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis. Support. Care Cancer 22, 2271–2280 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  107. Gonzalez, B. D. et al. Course and predictors of cognitive function in patients with prostate cancer receiving androgen-deprivation therapy: a controlled comparison. J. Clin. Oncol. 33, 2021–2027 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Alibhai, S. M. H. et al. Impact of androgen-deprivation therapy on cognitive function in men with nonmetastatic prostate cancer. J. Clin. Oncol. 28, 5030–5037 (2010).

    Article  CAS  PubMed  Google Scholar 

  109. Joly, F. et al. Impact of androgen deprivation therapy on physical and cognitive function, as well as quality of life of patients with nonmetastatic prostate cancer. J. Urol. 176, 2443–2447 (2006).

    Article  CAS  PubMed  Google Scholar 

  110. Cella, D., Nichol, M. B., Eton, D., Nelson, J. B. & Mulani, P. Estimating clinically meaningful changes for the functional assessment of cancer therapy—prostate: results from a clinical trial of patients with metastatic hormone-refractory prostate cancer. Value Health 12, 124–129 (2009).

    Article  PubMed  Google Scholar 

  111. Cella, D., Eton, D. T., Lai, J.-S., Peterman, A. H. & Merkel, D. E. Combining anchor and distribution-based methods to derive minimal clinically important differences on the Functional Assessment of Cancer Therapy (FACT) anemia and fatigue scales. J. Pain Symptom Manage. 24, 547–561 (2002).

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Urology, Herlev and Gentofte University Hospital, Herlev Ringvej 75, 2730, Herlev, Denmark

    Peter Busch Østergren & Jens Sønksen

  2. Department of Endocrinology, Herlev and Gentofte University Hospital, Herlev Ringvej 75, 2730, Herlev, Denmark

    Caroline Kistorp, Finn Noe Bennedbæk & Jens Faber

  3. Department of Urology, Roskilde University Hospital, Køgevej 7–13, Roskilde, 4000, Denmark

    Mikkel Fode

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Contributions

P.B.Ø. researched data for the article and wrote the manuscript. All authors substantially contributed to discussion of the article content and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Peter Busch Østergren.

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Competing interests

J.S. is a speaker for Astellas, consultant and speaker for Eli Lilly, Menarini and Coloplast, and board member and shareholder of Multicept. M.F. is a consultant and speaker for Eli Lilly, Astellas and Menarini. P.B.Ø., C.K., F.N.B. and J.F. do not declare any competing interests.

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Østergren, P., Kistorp, C., Bennedbæk, F. et al. The use of exercise interventions to overcome adverse effects of androgen deprivation therapy. Nat Rev Urol 13, 353–364 (2016). https://doi.org/10.1038/nrurol.2016.67

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