Muscle and bone effects of androgen deprivation therapy: Current and emerging therapies

Endocrine-Related Cancer

Volumn 21, Issue 5, 2014, Pages R371-R394

  Cheung, Ada S ^a,b   Zajac, Jeffrey D ^a,b   Grossmann, Mathis ^a,b  

^a AUSTIN HEALTH   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Androgen deprivation; Cardiovascular diseases; Muscle; Osteoporosis; Prostatic neoplasms

Indexed keywords

ANTIANDROGEN; ANTINEOPLASTIC HORMONE AGONISTS AND ANTAGONISTS;

ANIMAL; BONE; BONE DISEASES; CHEMICALLY INDUCED; DRUG EFFECTS; HUMAN; MALE; METABOLISM; MUSCULAR ATROPHY; PROSTATIC NEOPLASMS; SKELETAL MUSCLE;

ANDROGEN ANTAGONISTS; ANIMALS; ANTINEOPLASTIC AGENTS, HORMONAL; BONE AND BONES; BONE DISEASES; HUMANS; MALE; MUSCLE, SKELETAL; MUSCULAR ATROPHY; PROSTATIC NEOPLASMS;

EID: 84907482751     PISSN: 13510088     EISSN: 14796821     Source Type: Journal    
DOI: 10.1530/ERC-14-0172     Document Type: Review

References (124)

1. Alibhai SM, Breunis H, Timilshina N, Johnston C, Tomlinson G, Tannock I, Krahn M, Fleshner NE, Warde P, Canning SD et al. 2010a Impact of androgen-deprivation therapy on physical function and quality of life in men with nonmetastatic prostate cancer. Journal of Clinical Oncology 28 5038-5045. (doi:10.1200/JCO.2010.29.8091)
2. Alibhai SM, Duong-Hua M, Cheung AM, Sutradhar R, Warde P, Fleshner NE & Paszat L 2010b Fracture types and risk factors in men with prostate cancer on androgen deprivation therapy: a matched cohort study of 19, 079 men. Journal of Urology 184 918-923. (doi:10.1016/j.juro.2010.04.068)
3. Basaria S & Bhasin S 2012 Targeting the skeletal muscle-metabolism axis in prostate-cancer therapy. New England Journal of Medicine 367 965-967.(doi:10.1056/NEJMcibr1203160)
4. Basaria S, LiebJ II, Tang AM, DeWeese T, Carducci M, Eisenberger M & Dobs AS2002 Long-term effects of androgen deprivation therapy inprostate cancer patients. Clinical Endocrinology 56 779-786.(doi:10.1046/j.1365-2265.2002.01551.x)
5. Basaria S, Collins L, Dillon EL, Orwoll K, Storer TW, Miciek R, Ulloor J, Zhang A, Eder R, Zientek H et al. 2013 The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 68 87-95.(doi:10.1093/gerona/gls078)
6. Beebe-Dimmer JL, Cetin K, Shahinian V, Morgenstern H, Yee C, Schwartz KL & Acquavella J 2012 Timing of androgen deprivation therapy use and fracture risk among elderly men with prostate cancer in the United States. Pharmacoepidemiology and Drug Safety 21 70-78. (doi:10.1002/pds.2258)
7. Berruti A, Dogliotti L, Terrone C, Cerutti S, Isaia G, Tarabuzzi R, ReimondoG, Mari M, Ardissone P, De Luca S et al. 2002 Changes in bone mineral density, lean body mass and fat content as measured by dual energy X-ray absorptiometry in patients with prostate cancer without apparent bone metastases given androgen deprivation therapy. Journal of Urology 167 2361-2367 (discussion 2367). (doi:10.1016/S0022-5347(05)64985-3)
8. Bhasin S, Jasuja R, Tu P, Storer TW & Guo W 2011 Novel strategies for improving physical function. Hormone Research in Paediatrics 76 (Suppl 1) 17-23. (doi:10.1159/000329148)
9. Bhoopalam N, Campbell SC, Moritz T, Broderick WR, Iyer P, Arcenas AG, Van Veldhuizen PJ, Friedman N, Reda D, Warren S et al. 2009 Intravenous zoledronic acid to prevent osteoporosis in a veteran population with multiple risk factors for bone loss on androgen deprivation therapy. Journal of Urology 182 2257-2264. (doi:10.1016/j.juro.2009.07.046)
10. Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C et al. 2002 Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet 360 103-106. (doi:10.1016/S0140-6736(02)09408-4)
11. Bolla M, de Reijke TM, Van Tienhoven G, Van den Bergh AC, Oddens J, Poortmans PM, Gez E, Kil P, Akdas A, Soete G et al. 2009 Duration of androgen suppression in the treatment of prostate cancer. New England Journal of Medicine 360 2516-2527. (doi:10.1056/NEJMoa0810095)
12. Bonaiuti D, Shea B, Iovine R, Negrini S, Robinson V, Kemper HC, Wells G, Tugwell P & Cranney A 2002 Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database of Systematic Reviews 2002 Issue 2 CD000333. (doi:10.1002/14651858.CD000333)
13. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F et al. 2011 Abiraterone and increased survivalin metastatic prostate cancer. New England Journal of Medicine 364 1995-2005. (doi:10.1056/NEJMoa1014618)
14. Bourke L, Doll H, Crank H, Daley A, Rosario D & Saxton JM 2011 Lifestyleintervention in men with advanced prostate cancer receiving androgen suppression therapy: a feasibility study. Cancer Epidemiology, Biomarkers & Prevention 20 647-657. (doi:10.1158/1055-9965.EPI-10-1143)
15. Boxer RS, Kenny AM, Dowsett R & Taxel P 2005 The effect of 6 months of androgen deprivation therapy on muscle and fat mass in older men with localized prostate cancer. Aging Male 8 207-212. (doi:10.1080/13685530500361226)
16. Brown JE, Ellis SP, Lester JE, Gutcher S, Khanna T, Purohit OP, McCloskey E & Coleman RE 2007 Prolonged efficacy of a single dose of the bisphosphonate zoledronic acid. Clinical Cancer Research 13 5406-5410. (doi:10.1158/1078-0432.CCR-07-0247)
17. Bylow K, Dale W, Mustian K, Stadler WM, Rodin M, Hall W, Lachs M &Mohile SG 2008 Falls and physical performance deficits in older patients with prostate cancer undergoing androgen deprivation therapy. Urology 72 422-427. (doi:10.1016/j.urology.2008.03.032)
18. Bylow K, Hemmerich J, Mohile SG, Stadler WM, Sajid S & Dale W 2011 Obese frailty, physical performance deficits, and falls in older men with biochemical recurrence of prostate cancer on androgen deprivation therapy: a case-control study. Urology 77 934-940. (doi:10.1016/j.urology.2010.11.024)
19. Cannata DH, Kirschenbaum A & Levine AC 2012 Androgen deprivation therapy as primary treatment for prostate cancer. Journal of Clinical Endocrinology and Metabolism 97 360-365. (doi:10.1210/jc.2011-2353)
20. Carmack Taylor CL, Demoor C, Smith MA, Dunn AL, Basen-Engquist K, Nielsen I, Pettaway C, Sellin R, Massey P & Gritz ER 2006 Active for Life After Cancer: a randomized trial examining a lifestyle physical activity program for prostate cancer patients. Psycho-Oncology 15 847-862.(doi:10.1002/pon.1023)
21. Casey R, Gesztesi Z & Rochford J 2010 Long term zoledronic acid during androgen blockade for prostate cancer. Canadian Journal of Urology 17 5170-5177.
22. Casey RG, Corcoran NM & Goldenberg SL 2012 Quality of life issues in men undergoing androgen deprivation therapy: a review. Asian Journal of Andrology 14 226-231. (doi:10.1038/aja.2011.108)
23. Cheung AS, Pattison D, Bretherton I, Hoermann R, Lim Joon D, Ho E, Jenkins T, Hamilton EJ, Bate K, Chan I et al. 2013 Cardiovascular risk and bone loss in men undergoing androgen deprivation therapy fornon-metastatic prostate cancer: implementation of standardized management guidelines. Andrology 1 583-589. (doi:10.1111/j.2047-2927.2013.00093.x)
24. Choo R, Lukka H, Cheung P, Corbett T, Briones-Urbina R, Vieth R, Ehrlich L, Kiss A & Danjoux C 2013 Randomized, double-blinded, placebocontrolled, trial of risedronate for the prevention of bone mineral density loss in nonmetastatic prostate cancer patients receiving radiation therapyplus androgen deprivation therapy. International Journal of Radiation Oncology, Biology, Physics 85 1239-1245. (doi:10.1016/j.ijrobp.2012.11.007)
25. Clay CA, Perera S, Wagner JM, Miller ME, Nelson JB & Greenspan SL 2007 Physical function in men with prostate cancer on androgen deprivation therapy. Physical Therapy 87 1325-1333. (doi:10.2522/ptj.20060302)
26. Cormie P, Galvao DA, Spry N, Joseph D, Chee R, Taaffe DR, Chambers SK &Newton RU 2014 Can supervised exercise prevent treatment toxicity in prostate cancer patients initiating androgen deprivation therapy: a randomised controlled trial. BJU International [in press]. (doi:10.1111/bju.12646)
27. Crawford J, Prado CMM, Hancock ML, Johnston MA, Dalton JT & Steiner MS 2013 Abstract P3.11-026: Results from two phase 3 randomized trials of enobosarm, selective androgen receptor modulator (SARM), for the prevention and treatment of muscle wasting in NSCLC. In 15th World Congress on Lung Cancer. Sydney, Australia: International Association for the Study of Lung Cancer.
28. Culos-Reed SN, Robinson JL, Lau H, O'Connor K & Keats MR 2007 Benefits of a physical activity intervention for men with prostate cancer. Journal of Sport & Exercise Psychology 29 118-127.
29. Culos-Reed SN, Robinson JW, Lau H, Stephenson L, Keats M, Norris S, KlineG & Faris P 2010 Physical activity for men receiving androgen deprivation therapy for prostate cancer: benefits from a 16-week intervention. Supportive Care in Cancer 18 591-599. (doi:10.1007/s00520-009-0694-3)
30. Dalton JT, Barnette KG, Bohl CE, Hancock ML, Rodriguez D, Dodson ST, Morton RA & Steiner MS 2011 The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial.Journal of Cachexia, Sarcopenia and Muscle 2 153-161. (doi:10.1007/s13539-011-0034-6)
31. Denham JW, Nowitz M, Joseph D, Duchesne G, Spry NA, Lamb DS, Matthews J, Turner S, Atkinson C, Tai KH et al. 2013 Impact of androgen suppression and zoledronic acid on bone mineral density and fractures in the Trans-Tasman Radiation Oncology Group (TROG) 03.04 Randomised Androgen Deprivation and Radiotherapy (RADAR)randomized controlled trial for locally advanced prostate cancer. BJU International [in press]. (doi:10.1111/bju.12497)
32. Diamond TH, Winters J, Smith A, De Souza P, Kersley JH, Lynch WJ &Bryant C 2001 The antiosteoporotic efficacy of intravenous pamidronatein men with prostate carcinoma receiving combined androgen blockade: a double blind, randomized, placebo-controlled crossover study. Cancer 92 1444-1450. (doi:10.1002/1097-0142(20010915)92:6!1444::AID-CNCR1468O3.0.CO;2-M)
33. Dobs AS, Boccia RV, Croot CC, Gabrail NY, Dalton JT, Hancock ML, Johnston MA & Steiner MS 2013 Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncology 14 335-345.(doi:10.1016/S1470-2045(13)70055-X)
34. Dorff TB, Flaig TW, Tangen CM, Hussain MH, Swanson GP, Wood DP Jr, Sakr WA, Dawson NA, Haas NB, Crawford ED et al. 2011 Adjuvant androgen deprivation for high-risk prostate cancer after radicalprostatectomy: SWOG S9921 study. Journal of Clinical Oncology 29 2040-2045. (doi:10.1200/JCO.2010.32.2776)
35. Ebeling PR 2008 Clinical practice. Osteoporosis in men. New England Journal of Medicine 358 1474-1482. (doi:10.1056/NEJMcp0707217)
36. Falahati-Nini A, Riggs BL, Atkinson EJ, O'Fallon WM, Eastell R & Khosla S2000 Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. Journal of Clinical Investigation 106 1553-1560. (doi:10.1172/JCI10942)
37. Finkelstein JS, Lee H, Burnett-Bowie SA, Pallais JC, Yu EW, Borges LF, Jones BF, Barry CV, Wulczyn KE, Thomas BJ et al. 2013 Gonadal steroids and body composition, strength, and sexual function in men. New England Journal of Medicine 369 1011-1022. (doi:10.1056/NEJMoa1206168)
38. Fizazi K, Massard C, Bono P, Jones R, Kataja V, James N, Garcia JA, Protheroe A, Tammela TL, Elliott T et al. 2014 Activity and safety of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (ARADES): an open-label phase 1 dose-escalation and randomised phase 2 dose expansion trial. Lancet Oncology 15 975-985.(doi:10.1016/S1470-2045(14)70240-2)
39. Galvao DA, Spry NA, Taaffe DR, Newton RU, Stanley J, Shannon T, Rowling C & Prince R 2008 Changes in muscle, fat and bone mass after 36 weeks of maximal androgen blockade for prostate cancer. BJU International 102 44-47. (doi:10.1111/j.1464-410X.2008.07539.x)
40. Galvao DA, Taaffe DR, Spry N, Joseph D, Turner D & Newton RU 2009a Reduced muscle strength and functional performance in men with prostate cancer undergoing androgen suppression: a comprehensive cross-sectional investigation. Prostate Cancer and Prostatic Diseases 12 198-203. (doi:10.1038/pcan.2008.51)
41. Galvao DA, Spry N, Taaffe DR, Denham J, Joseph D, Lamb DS, Levin G, Duchesne G & Newton RU 2009b A randomized controlled trial of an exercise intervention targeting cardiovascular and metabolic risk factors for prostate cancer patients from the RADAR trial. BMC Cancer 9 419. (doi:10.1186/1471-2407-9-419)
42. Galvao DA, Taaffe DR, Spry N, Joseph D & Newton RU 2010 Combinedresistance and aerobic exercise program reverses muscle loss in men undergoing androgen suppression therapy for prostate cancer without bone metastases: a randomized controlled trial. Journal of Clinical Oncology 28 340-347. (doi:10.1200/JCO.2009.23.2488)
43. Gao W, Kearbey JD, Nair VA, Chung K, Parlow AF, Miller DD & Dalton JT2004 Comparison of the pharmacological effects of a novel selective androgen receptor modulator, the 5a-reductase inhibitor finasteride, and the antiandrogen hydroxyflutamide in intact rats: new approach for benign prostate hyperplasia. Endocrinology 145 5420-5428.(doi:10.1210/en.2004-0627)
44. Garcia-Fontana B, Morales-Santana S, Varsavsky M, Garcia-Martin A, Garcia-Salcedo JA, Reyes-Garcia R & Munoz-Torres M 2014 Sclerostin serum levels in prostate cancer patients and their relationship with sex steroids. Osteoporosis International 25 645-651. (doi:10.1007/s00198-013-2462-y)
45. Gardner JR, Livingston PM & Fraser SF 2014 Effects of exercise on treatment-related adverse effects for patients with prostate cancer receiving androgen-deprivation therapy: a systematic review. Journal of Clinical Oncology 32 335-346. (doi:10.1200/JCO.2013.49.5523)
46. Greenspan SL 2008 Approach to the prostate cancer patient with bone disease. Journal of Clinical Endocrinology and Metabolism 93 2-7.(doi:10.1210/jc.2007-1402)
47. Greenspan SL, Coates P, Sereika SM, Nelson JB, Trump DL & Resnick NM2005 Bone loss after initiation of androgen deprivation therapy inpatients with prostate cancer. Journal of Clinical Endocrinology and Metabolism 90 6410-6417. (doi:10.1210/jc.2005-0183)
48. Greenspan SL, Nelson JB, Trump DL & Resnick NM 2007 Effect of once weekly oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer: a randomized trial. Annals of Internal Medicine 146 416-424. (doi:10.7326/0003-4819-146-6-200703200-00006)
49. Greenspan SL, Nelson JB, Trump DL, Wagner JM, Miller ME, Perera S &Resnick NM 2008 Skeletal health after continuation, withdrawal, or delay of alendronate in men with prostate cancer undergoing androgen-deprivation therapy. Journal of Clinical Oncology 26 4426-4434. (doi:10.1200/JCO.2007.15.1233)
50. Greenspan SL, Wagner J, Nelson JB, Perera S, Britton C & Resnick NM 2012 Vertebral fractures and trabecular microstructure in men with prostate cancer on androgen deprivation therapy. Journal of Bone and Mineral Research 28 325-366. (doi:10.1002/jbmr.1771)
51. Grossmann M & Zajac JD 2011 Androgen deprivation therapy in men with prostate cancer: how should the side effects be monitored and treated? Clinical Endocrinology 74 289-293. (doi:10.1111/j.1365-2265.2010.03939.x)
52. Grossmann M & Zajac JD 2012 Hematological changes during androgen deprivation therapy. Asian Journal of Andrology 14 187-192.(doi:10.1038/aja.2011.102)
53. Grossmann M, Hamilton EJ, Gilfillan C, Bolton D, Joon DL & Zajac JD 2011 Bone and metabolic health in patients with non-metastatic prostate cancer who are receiving androgen deprivation therapy. Medical Journal of Australia 194 301-306.
54. Grossmann M, Cheung AS & Zajac JD 2013 Androgens and prostate cancer;pathogenesis and deprivation therapy. Best Practice & Research. Clinical Endocrinology & Metabolism 27 603-616. (doi:10.1016/j.beem.2013.05.001)
55. Hamilton EJ, Ghasem-Zadeh A, Gianatti E, Lim-Joon D, Bolton D, Zebaze R, Seeman E, Zajac JD & Grossmann M 2010 Structural decay of bone microarchitecture in men with prostate cancer treated with androgen deprivation therapy. Journal of Clinical Endocrinology and Metabolism 95 E456-E463. (doi:10.1210/jc.2010-0902)
56. Horwitz EM, Bae K, Hanks GE, Porter A, Grignon DJ, Brereton HD, Venkatesan V, Lawton CA, Rosenthal SA, Sandler HM et al. 2008 Ten-year follow-up of radiation therapy oncology group protocol 92-02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. Journal of Clinical Oncology 26 2497-2504. (doi:10.1200/JCO.2007.14.9021)
57. Huggins C & Hodges C 1941a 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 Research 19 293-297. (doi:10.1016/S0022-5347(02)80307-X)
58. Huggins C & Hodges C 1941b Studies on prostatic cancer II: the effects of castration on advanced carcinoma of the prostate gland. Archives of Surgery 43 209-223. (doi:10.1001/archsurg.1941.01210140043004)
59. Israeli RS, Rosenberg SJ, Saltzstein DR, Gottesman JE, Goldstein HR, Hull GW, Tran DN, Warsi GM & Lacerna LV 2007 The effect of zoledronic acid on bone mineral density in patients undergoing androgen deprivation therapy. Clinical Genitourinary Cancer 5 271-277.(doi:10.3816/CGC.2007.n.003)
60. Izumi K, Mizokami A, Sugimoto K, Narimoto K, Miwa S, Maeda Y, Kadono Y, TakashimaM, Koh E & NamikiM2009 Risedronate recovers bone loss inpatients with prostate cancer undergoing androgen-deprivation therapy. Urology 73 1342-1346. (doi:10.1016/j.urology.2009.01.046)
61. Izumi K, Mizokami A, Sugimoto K, Narimoto K, Kitagawa Y, Koh E & Namiki M 2011 Risedronate prevents persistent bone loss in prostate cancer patients treated with androgen deprivation therapy: results of a 2-year follow-up study. Prostate Cancer and Prostatic Diseases 14 238-242. (doi:10.1038/pcan.2011.10)
62. Jamadar RJ, WintersMJ & Maki PM 2012 Cognitive changes associated with ADT: a review of the literature. Asian Journal of Andrology 14 232-238.(doi:10.1038/aja.2011.107)
63. Joly F, Alibhai SM, Galica J, Park A, Yi QL, Wagner L & Tannock IF 2006 Impact of androgen deprivation therapy on physical and cognitive function, as well as quality of life of patients with nonmetastatic prostate cancer. Journal of Urology 176 2443-2447. (doi:10.1016/j.juro.2006.07.151)
64. Kapoor A, Gupta A, Desai N & Ahn H 2011 Effect of zoledronic acid on bone mineral density in men with prostate cancer receiving gonadotropin releasing hormone analog. Prostate Cancer 2011 176164. (doi:10.1155/2011/176164)
65. Ke HZ, Richards WG, Li X & Ominsky MS 2012 Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocrine Reviews 33 747-783.(doi:10.1210/er.2011-1060)
66. Keogh JW & MacLeod RD 2012 Body composition, physical fitness, functional performance, quality of life, and fatigue benefits of exercise for prostate cancer patients: a systematic review. Journal of Pain and Symptom Management 43 96-110. (doi:10.1016/j.jpainsymman.2011.03.006)
67. Klotz LH, McNeill IY, Kebabdjian M, Zhang L, Chin JL & Canadian Urology Research Consortium. 2013 A phase 3, double-blind, randomised, parallel-group, placebo-controlled study of oral weekly alendronate for the prevention of androgen deprivation bone loss in nonmetastatic prostate cancer: the Cancer and Osteoporosis Research with Alendronate and Leuprolide (CORAL) study. European Urology 63 927-935.(doi:10.1016/j.eururo.2012.09.007)
68. Klotz L, Miller K, Crawford ED, Shore N, Tombal B, Karup C, Malmberg A &Persson BE 2014 Disease control outcomes from analysis of pooled individual patient data from five comparative randomised clinical trials of degarelix versus luteinising hormone-releasing hormone agonists. European Urology [in press]. (doi:10.1016/j.eururo.2013.12.063)
69. Lee SJ 2007 Quadrupling muscle mass in mice by targeting TGF-b signaling pathways. PLoS ONE 2 e789. (doi:10.1371/journal.pone.0000789)
70. Levy ME, Perera S, van Londen GJ, Nelson JB, Clay CA & Greenspan SL 2008 Physical function changes in prostate cancer patients on androgen deprivation therapy: a 2-year prospective study. Urology 71 735-739.(doi:10.1016/j.urology.2007.09.018)
71. Mauras N, Hayes V, Welch S, Rini A, Helgeson K, Dokler M, Veldhuis JD &Urban RJ 1998 Testosterone deficiency in young men: marked alterations in whole body protein kinetics, strength, and adiposity. Journal of Clinical Endocrinology and Metabolism 83 1886-1892.(doi:10.1210/jcem.83.6.4892)
72. Mazzola CR & Mulhall JP 2012 Impact of androgen deprivation therapy on sexual function. Asian Journal of Andrology 14 198-203. (doi:10.1038/aja.2011.106)
73. McClung MR, Grauer A, Boonen S, Bolognese MA, Brown JP, Diez-Perez A, Langdahl BL, Reginster JY, Zanchetta JR, Wasserman SM et al. 2014 Romosozumab in postmenopausal women with low bone mineral density. New England Journal of Medicine 370 412-420. (doi:10.1056/NEJMoa1305224)
74. Mellstrom D, Vandenput L, MallminH, Holmberg AH, Lorentzon M, OdenA, Johansson H, Orwoll ES, Labrie F, Karlsson MK et al. 2008 Older men with low serum estradiol and high serum SHBG have an increased risk of fractures. Journal of Bone and Mineral Research 23 1552-1560.(doi:10.1359/jbmr.080518)
75. Melton LJ III, Atkinson EJ, O'Connor MK, O'Fallon WM & Riggs BL 1998 Bone density and fracture risk in men. Journal of Bone and Mineral Research 13 1915-1923. (doi:10.1359/jbmr.1998.13.12.1915)
76. Messing EM, Manola J, Yao J, Kiernan M, Crawford D, Wilding G, di'Sant Agnese PA & Trump D 2006 Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelviclymphadenectomy. Lancet Oncology 7 472-479. (doi:10.1016/S1470-2045(06)70700-8)
77. MichaelsonMD, Kaufman DS, Lee H, McGovern FJ, Kantoff PW, Fallon MA, Finkelstein JS & Smith MR 2007 Randomized controlled trial of annualzoledronic acid to prevent gonadotropin-releasing hormone agonist induced bone loss in men with prostate cancer. Journal of Clinical Oncology 25 1038-1042. (doi:10.1200/JCO.2006.07.3361)
78. Morabito N, Gaudio A, Lasco A, Catalano A, Atteritano M, Trifiletti A, Anastasi G, Melloni D & Frisina N 2004 Neridronate prevents bone lossin patients receiving androgen deprivation therapy for prostate cancer. Journal of Bone and Mineral Research 19 1766-1770. (doi:10.1359/JBMR.040813)
79. Nabid A, Carrier N, Martin A, Bahary J, Souhami L, Duclos M, Vincent F, Vass S, Bahoric B, Archambault R et al. 2013 Duration of androgendeprivation therapy in high-risk prostate cancer: a randomized trial. Journal of Clinical Oncology 31 (suppl; abstr LBA4510)
80. Newton RU, Taaffe DR, Spry N, Gardiner RA, Levin G, Wall B, Joseph D, Chambers SK & Galvao DA 2009 A phase III clinical trial of exercise modalities on treatment side-effects in men receiving therapy for prostate cancer. BMC Cancer 9 210. (doi:10.1186/1471-2407-9-210)
81. Ng Tang Fui M, Dupuis P & Grossmann M 2014 Lowered testosterone in male obesity: mechanisms, morbidity and management. Asian Journal of Andrology 16 223-231. (doi:10.4103/1008-682X.122365)
82. Ost P, Cozzarini C, DeMeerleer G, Fiorino C, DePotter B, Briganti A, Nagler EV, Montorsi F, Fonteyne V & Di Muzio N 2012 High-dose adjuvant radiotherapy after radical prostatectomy with or without androgen deprivation therapy. International Journal of Radiation Oncology, Biology, Physics 83 960-965. (doi:10.1016/j.ijrobp.2011.09.007)
83. Padhi D, Higano CS, Shore N, Sieber P, Rasmussen E & Smith MR 2014 Pharmacologic inhibition of myostatin and changes in lean body mass and lower extremity muscle size in patients receiving androgen deprivation therapy for prostate cancer. Journal of Clinical Endocrinology and Metabolism [in press]. (doi:10.1210/jc.2014-1271)
84. Papanicolaou DA, Ather SN, Zhu H, Zhou Y, Lutkiewicz J, Scott BB &Chandler J 2013 A phase IIA randomized, placebo-controlled clinical trial to study the efficacy and safety of the selective androgen receptormodulator (SARM), MK-0773 in female participants with sarcopenia.Journal of Nutrition, Health & Aging 17 533-543. (doi:10.1007/s12603-013-0335-x)
85. Pedersen BK 2011 Muscles and their myokines. Journal of Experimental Biology 214 337-346. (doi:10.1242/jeb.048074)
86. Pedersen BK & Febbraio MA 2012 Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nature Reviews. Endocrinology 8 457-465.(doi:10.1038/nrendo.2012.49)
87. Pezaro C, Mukherji D, Tunariu N, Cassidy AM, Omlin A, Bianchini D, Seed G, Reid AH, Olmos D, de Bono JS et al. 2013 Sarcopenia and change inbody composition following maximal androgen suppression with abiraterone in men with castration-resistant prostate cancer. British Journal of Cancer 109 325-331. (doi:10.1038/bjc.2013.340)
88. Pilepich MV, Winter K, Lawton CA, Krisch RE, Wolkov HB, Movsas B, Hug EB,Asbell SO & Grignon D 2005 Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma - long-term results of phase III RTOG 85-31. International Journal of Radiation Oncology, Biology, Physics 61 1285-1290. (doi:10.1016/j.ijrobp.2004.08.047)
89. Preston DM, Torrens JI, Harding P, Howard RS, Duncan WE & McLeod DG2002 Androgen deprivation in men with prostate cancer is associated with an increased rate of bone loss. Prostate Cancer and Prostatic Diseases 5 304-310. (doi:10.1038/sj.pcan.4500599)
90. Rana K, Fam BC, Clarke MV, Pang TP, Zajac JD & MacLean HE 2011 Increased adiposity in DNA binding-dependent androgen receptor knockout male mice associated with decreased voluntary activity and not insulin resistance. American Journal of Physiology. Endocrinology and Metabolism 301 E767-E778. (doi:10.1152/ajpendo.00584.2010)
91. Rodrigues P, Meler A & Hering F 2010 Titration of dosage for the protective effect of zoledronic acid on bone loss in patients submitted to androgen deprivation therapy due to prostate cancer: a prospective open-label study. Urologia Internationalis 85 180-185. (doi:10.1159/000314524)
92. Ryan CW, Huo D, Bylow K, Demers LM, Stadler WM, Henderson TO &Vogelzang NJ 2007 Suppression of bone density loss and bone turnoverin patients with hormone-sensitive prostate cancer and receiving zoledronic acid. BJU International 100 70-75. (doi:10.1111/j.1464-410X.2007.06853.x)
93. Sadagurski M, Norquay L, Farhang J, D'Aquino K, Copps K & White MF2010 Human IL6 enhances leptin action in mice. Diabetologia 53 525-535. (doi:10.1007/s00125-009-1580-8)
94. Satoh T, Kimura M, Matsumoto K, Tabata K, OkusaH, Bessho H, Iwamura M, Ishiyama H, Hayakawa K & Baba S 2009 Single infusion of zoledronic acid to prevent androgen deprivation therapy-induced bone loss in men with hormone-naive prostate carcinoma. Cancer 115 3468-3474.(doi:10.1002/cncr.24404)
95. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND et al. 2012 Increased survival with enzalutamide in prostate cancer after chemotherapy. New England Journal of Medicine 367 1187-1197. (doi:10.1056/NEJMoa1207506)
96. Schmitz KH, Courneya KS, Matthews C, Demark-Wahnefried W, Galvao DA, Pinto BM, Irwin ML, Wolin KY, Segal RJ, Lucia A et al. 2010 American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Medicine and Science in Sports and Exercise 42 1409-1426.(doi:10.1249/MSS.0b013e3181e0c112)
97. Segal RJ, Reid RD, Courneya KS, Malone SC, Parliament MB, Scott CG, Venner PM, Quinney HA, Jones LW, D'Angelo ME et al. 2003 Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. Journal of Clinical Oncology 21 1653-1659. (doi:10.1200/JCO.2003.09.534)
98. Segal RJ, Reid RD, Courneya KS, Sigal RJ, Kenny GP, Prud'Homme DG, Malone SC, Wells GA, Scott CG & Slovinec D'Angelo ME 2009 Randomized controlled trial of resistance or aerobic exercise in men receiving radiation therapy for prostate cancer. Journal of Clinical Oncology 27 344-351. (doi:10.1200/JCO.2007.15.4963)
99. Serpa Neto A, Tobias-Machado M, Esteves MA, Senra MD, Wroclawski ML, Fonseca FL, Dos Reis RB, Pompeo AC & Giglio AD 2012 Bisphosphonate therapy in patients under androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis. Prostate Cancer and Prostatic Diseases 15 36-44. (doi:10.1038/pcan.2011.4)
100. Serra C, Sandor NL, Jang H, Lee D, Toraldo G, Guarneri T, Wong S, Zhang A, Guo W, Jasuja R et al. 2013 The effects of testosterone deprivation and supplementation on proteasomal and autophagy activity in the skeletal muscle of the male mouse: differential effects on high-androgen responder and low-androgen responder muscle groups. Endocrinology 154 4594-4606. (doi:10.1210/en.2013-1004)
101. Shahinian VB, Kuo YF, Freeman JL & Goodwin JS 2005 Risk of fracture after androgen deprivation for prostate cancer. New England Journal of Medicine 352 154-164. (doi:10.1056/NEJMoa041943)
102. Shahinian VB, Kuo YF & Gilbert SM 2010 Reimbursement policy and androgen-deprivation therapy for prostate cancer. New England Journal of Medicine 363 1822-1832. (doi:10.1056/NEJMsa0910784)
103. Smith MR 2004 Changes in fat and lean body mass during androgen deprivation therapy for prostate cancer. Urology 63 742-745.(doi:10.1016/j.urology.2003.10.063)
104. Smith MR 2007 Androgen deprivation therapy for prostate cancer: new concepts and concerns. Current Opinion in Endocrinology, Diabetes, and Obesity 14 247-254. (doi:10.1097/MED.0b013e32814db88c)
105. Smith MR, McGovern FJ, Zietman AL, Fallon MA, Hayden DL, Schoenfeld DA, Kantoff PW & Finkelstein JS 2001 Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. New England Journal of Medicine 345 948-955. (doi:10.1056/NEJMoa010845)
106. Smith MR, Finkelstein JS, McGovern FJ, Zietman AL, Fallon MA, Schoenfeld DA & Kantoff PW 2002 Changes in body composition during androgen deprivation therapy for prostate cancer. Journal of Clinical Endocrinology and Metabolism 87 599-603. (doi:10.1210/jcem.87.2.8299)
107. Smith MR, Eastham J, Gleason DM, Shasha D, Tchekmedyian S & Zinner N2003 Randomized controlled trial of zoledronic acid to prevent boneloss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. Journal of Urology 169 2008-2012. (doi:10.1097/01.ju.0000063820.94994.95)
108. Smith MR, Egerdie B, Hernandez Toriz N, Feldman R, Tammela TL, Saad F, Heracek J, Szwedowski M, Ke C, Kupic A et al. 2009a Denosumab in men receiving androgen-deprivation therapy for prostate cancer. New England Journal of Medicine 361 745-755. (doi:10.1056/NEJMoa0809003)
109. Smith MR, Saad F, Egerdie B, Szwedowski M, Tammela TL, Ke C, Leder BZ &Goessl C 2009b Effects of denosumab on bone mineral density in menreceiving androgen deprivation therapy for prostate cancer. Journal of Urology 182 2670-2675. (doi:10.1016/j.juro.2009.08.048)
110. Smith MR, Saad F, Egerdie B, Sieber P, Tammela T, Leder BZ, Ke C &Goessl C 2011 Denosumab and changes in bone turnover markers during androgen deprivation therapy for prostate cancer. Journal of Bone and Mineral Research 26 2827-2833. (doi:10.1002/jbmr.492)
111. Smith MR, Saad F, Egerdie B, Sieber PR, Tammela TL, Ke C, Leder BZ &Goessl C 2012 Sarcopenia during androgen-deprivation therapy for prostate cancer. Journal of Clinical Oncology 30 3271-3276.(doi:10.1200/JCO.2011.38.8850)
112. Soyupek F, Soyupek S, Perk H & Ozorak A 2008 Androgen deprivation therapy for prostate cancer: effects on hand function. Urologic Oncology 26 141-146. (doi:10.1016/j.urolonc.2006.12.014)
113. Spry NA, Taaffe DR, England PJ, Judge JS, Stephens DA, Peddle-McIntyre C, Baker MK, Newton RU & Galvao DA 2013 Long-term effects of intermittent androgen suppression therapy on lean and fat mass: a 33-month prospective study. Prostate Cancer and Prostatic Diseases 16 67-72. (doi:10.1038/pcan.2012.33)
114. Stone P, Hardy J, Huddart R, A'Hern R & Richards M 2000 Fatigue inpatients with prostate cancer receiving hormone therapy. European Journal of Cancer 36 1134-1141. (doi:10.1016/S0959-8049(00)00084-8)
115. Storer TW, Miciek R & Travison TG 2012 Muscle function, physical performance and body composition changes in men with prostate cancer undergoing androgen deprivation therapy. Asian Journal of Andrology 14 204-221. (doi:10.1038/aja.2011.104)
116. Tang BM, Eslick GD, Nowson C, Smith C & Bensoussan A 2007 Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 370 657-666. (doi:10.1016/S0140-6736(07)61342-7)
117. Tesei A, Leonetti C, Di Donato M, Gabucci E, Porru M, Varchi G, Guerrini A, Amadori D, Arienti C, Pignatta S et al. 2013 Effect of small molecules modulating androgen receptor (SARMs) in human prostate cancer models. PLoS ONE 8 e62657. (doi:10.1371/journal.pone.0062657)
118. Tu P, Bhasin S, Hruz PW, Herbst KL, Castellani LW, Hua N, Hamilton JA &GuoW2009 Genetic disruption of myostatin reduces the development of proatherogenic dyslipidemia and atherogenic lesions in Ldlr nullmice. Diabetes 58 1739-1748. (doi:10.2337/db09-0349)
119. Van Hemelrijck M, Garmo H, Michaelsson K, Thorstenson A, Akre O, Stattin P, Holmberg L & Adolfsson J 2013 Mortality following hip fracture in men with prostate cancer. PLoS ONE 8 e74492. (doi:10.1371/journal.pone.0074492)
120. Waters DL & Baumgartner RN 2011 Sarcopenia and obesity. Clinics in Geriatric Medicine 27 401-421. (doi:10.1016/j.cger.2011.03.007)
121. Winters-Stone KM, Dobek JC, Bennett JA, Maddalozzo GF, Ryan CW &Beer TM 2014 Skeletal response to resistance and impact training in prostate cancer survivors. Medicine and Science in Sports and Exercise 46 1482-1488. (doi:10.1249/MSS.0000000000000265)
122. Yang L, Sycheva AV, Black DM & Eastell R 2013 Site-specific differential effects of once-yearly zoledronic acid on the hip assessed with quantitative computed tomography: results from the HORIZON Pivotal Fracture Trial. Osteoporosis International 24 329-338. (doi:10.1007/s00198-012-2200-x)
123. Yu EY, Getzenberg RH, Coss CC, Gittelman MM, Keane T, Tutrone R, Belkoff L, Given R, Bass J, Chu F et al. 2014 Selective estrogen receptor aagonist GTx-758 decreases testosterone with reduced side effects of androgen deprivation therapy in men with advanced prostate cancer. European Urology [in press]. (doi:10.1016/j.eururo.2014.06.011)
124. Ziaran S, Goncalves FM & Sn JB 2013 Complex metabolic and skeletal changes in men taking long-term androgen deprivation therapy. Clinical Genitourinary Cancer 11 33-38. (doi:10.1016/j.clgc.2012.08.005)