Is Testosterone a Friend or a Foe of the Prostate?

Journal of Sexual Medicine

Volumn 8, Issue 4, 2011, Pages 946-955

  Jannini, Emmanuele A ^a   Gravina, Giovanni L ^a   Mortengaler, Abraham ^b   Morales, Alvaro ^c   Incrocci, Luca ^d   Hellstrom, Wayne J G ^e  

^a UNIVERSITY OF L'AQUILA   (Italy)

^b HARVARD MEDICAL SCHOOL   (United States)

^c QUEEN S UNIVERSITY   (Canada)

^d ERASMUS MEDICAL CENTER   (Netherlands)

^e TULANE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cancer; Erectile Dysfunction; Prostate; Testosterone; Treatment

Indexed keywords

ANDROGEN RECEPTOR; ANDROSTANOLONE; PROSTATE SPECIFIC ANTIGEN; TESTOSTERONE;

ANDROGEN DEFICIENCY; ARTICLE; CONCENTRATION RESPONSE; DRUG EFFECT; HORMONE ACTION; HORMONE RESPONSE; HORMONE SUBSTITUTION; HUMAN; HYPOGONADISM; MALE; MALE SEXUAL DYSFUNCTION; PRIORITY JOURNAL; PROSTATE; PROSTATE CANCER; PROSTATE HYPERTROPHY; TESTOSTERONE BLOOD LEVEL;

EID: 79953305847     PISSN: 17436095     EISSN: 17436109     Source Type: Journal    
DOI: 10.1111/j.1743-6109.2011.02233.x     Document Type: Article

References (51)

1. Isidori AM, Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, Lenzi A, Fabbri A. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: A meta-analysis. Clin Endocrinol 2005;63:280-93.
2. Isidori AM, Giannetta E, Gianfrilli D, Greco EA, Bonifacio V, Aversa A, Isidori A, Fabbri A, Lenzi A. Effects of testosterone on sexual function in men: Results of a meta-analysis. Clin Endocrinol 2005;63:381-94.
3. Rhoden EL, Averbeck MA, Teloken PE. Androgen replacement in men undergoing treatment for prostate cancer. J Sex Med 2008;5:2202-8.
4. Eaton NE, Reeves GK, Appleby PN, Key TJ. Endogenous sex hormones and prostate cancer: A quantitative review of prospective studies. Br J Cancer 1999;80:930-4.
5. Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, Morley JE, Schulman C, Thompson IM, Weidner W, Wu FC. Investigation, treatment and monitoring of late-onset hypogonadism in males. Int J Androl 2009;32:1-10.
6. Buvat J, Maggi M, Gooren L, Guay AT, Kaufman J, Morgentaler A, Schulman C, Tan HM, Torres LO, Yassin A, Zitzmann M. Endocrine aspects of male sexual dysfunctions. J Sex Med 2010;7:1627-56.
7. Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Mattelaer J, Lopez Torecilla J, Pfeffer JR, Lino Cutajar C, Zurlo A, Pierart M. 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 2002;360:103-6.
8. Denham JW, Steigler A, Lamb DS, Joseph D, Mameghan H, Turner S, Matthews J, Franklin I, Atkinson C, North J, Poulsen M, Christie D, Spry NA, Tai KH, Wynne C, Duchesne G, Kovacev O, D'Este C. Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: Results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial. Lancet Oncol 2005;6:841-50.
9. Albertsen PC, Hanley JA, Fine J. 20-year outcomes following conservative management of clinically localized prostate cancer. JAMA 2005;293:2095-101.
10. Gravina GL, Biordi L, Martella F, Flati V, Ricevuto E, Ficorella C, Tombolini V, Festuccia C. Epigenetic modulation of PTEN expression during antiandrogenic therapies in human prostate cancer. Int J Oncol 2009;35:1133-9.
11. Gravina GL, Festuccia C, Marampon F, Popov VM, Pestell RG, Zani BM, Tombolini V. Biological rationale for the use of DNA methyltransferase inhibitors as new strategy for modulation of tumor response to chemotherapy and radiation. Mol Cancer 2010;25:305.
12. Gravina GL, Marampon F, Di Staso M, Bonfili P, Vitturini A, Jannini EA, Pestell RG, Tombolini V, Festuccia C. 5-Azacitidine restores and amplifies the bicalutamide response on preclinical models of androgen receptor expressing or deficient prostate tumors. Prostate 2010;70:1166-78.
13. Vickers AJ, Cronin AM, Roobol MJ, Hugosson J, Jones JS, Kattan MW, Klein E, Hamdy F, Neal D, Donovan J, Parekh DJ, Ankerst D, Bartsch G, Klocker H, Horninger W, Benchikh A, Salama G, Villers A, Freedland SJ, Moreira DM, Schroder FH, Lilja H. The relationship between prostate-specific antigen and prostate cancer risk: The Prostate Biopsy Collaborative Group. Clin Cancer Res 2010;16:4374-81.
14. Andriole GL, Crawford ED, Grubb RL 3rd, Buys SS, Chia D, Church TR, Fouad MN, Gelmann EP, Kvale PA, Reding DJ, Weissfeld JL, Yokochi LA, O'Brien B, Clapp JD, Rathmell JM, Riley TL, Hayes RB, Kramer BS, Izmirlian G, Miller AB, Pinsky PF, Prorok PC, Gohagan JK, Berg CD. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009;360:1310-9.
15. Corona G, Boddi V, Lotti F, Gacci M, Carini M, De Vita G, Sforza A, Forti G, Mannucci E, Maggi M. The relationship of testosterone to prostate-specific antigen in men with sexual dysfunction. J Sex Med 2010;7:284-92.
16. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-33.
17. Pearson H. Hormone therapy: A dangerous elixir? Nature 2004;431:500-1.
18. Carosa E, Volpe R, Martini P, Brandetti F, Di Stasi SM, Lombardo F, Salacone P, Sgro P, Gandini L, Lenzi A, Jannini EA. Psychosocial issues of ART in aging male. J Endocrinol Invest 2005;28:117-21.
19. Huggins C, Hodges CV. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941;1:293-7.
20. Morgentaler A, Bruning CO 3rd, DeWolf WC. Occult prostate cancer in men with low serum testosterone levels. JAMA 1996;276:1904-6.
21. Morgentaler A, Rhoden EL. Prevalence of prostate cancer among hypogonadal men with prostate-specific antigen levels of 4.0ng/mL or less. Urology 2006;68:1263-7.
22. Yamamoto S, Yonese J, Kawakami S, Ohkubo Y, Tatokoro M, Komai Y, Takeshita H, Ishikawa Y, Fukui I. Preoperative serum testosterone level as an independent predictor of treatment failure following radical prostatectomy. Eur Urol 2007;52:696-701.
23. Rhoden EL, Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. N Engl J Med 2004;350:482-92.
24. Morgentaler A. Testosterone and prostate cancer: An historical perspective on a modern myth. Eur Urol 2006;50:935-9.
25. Morgentaler A. Testosterone therapy in men with prostate cancer: Scientific and ethical considerations. J Urol 2009;181:972-9.
26. Weber JP, Oesterling JE, Peters CA, Partin AW, Chan DW, Walsh PC. The influence of reversible androgen deprivation on serum prostate-specific antigen levels in men with benign prostatic hyperplasia. J Urol 1989;141:987-92.
27. Wright AS, Douglas RC, Thomas LN, Lazier CB, Rittmaster RS. Androgen-induced regrowth in the castrated rat ventral prostate: Role of 5alpha-reductase. Endocrinology 1999;140:4509-15.
28. Arnold JT, Le H, McFann KK, Blackman MR. Comparative effects of DHEA vs. testosterone, dihydrotestosterone, and estradiol on proliferation and gene expression in human LNCaP prostate cancer cells. Am J Physiol Endocrinol Metab 2005;288:E573-84.
29. Cooper CS, Perry PJ, Sparks AE, MacIndoe JH, Yates WR, Williams RD. Effect of exogenous testosterone on prostate volume, serum and semen prostate specific antigen levels in healthy young men. J Urol 1998;159:441-3.
30. Roddam AW, Allen NE, Appleby P, Key TJ. Endogenous sex hormones and prostate cancer: A collaborative analysis of 18 prospective studies. J Natl Cancer Inst 2008;100:170-83.
31. Marks LS, Mazer NA, Mostaghel E, Hess DL, Dorey FJ, Epstein JI, Veltri RW, Makarov DV, Partin AW, Bostwick DG, Macairan ML, Nelson PS. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: A randomized controlled trial. JAMA 2006;296:2351-61.
32. Traish AM, Williams DF, Hoffman ND, Wotiz HH. Validation of the exchange assay for the measurement of androgen receptors in human and dog prostates. Prog Clin Biol Res 1988;262:145-60.
33. Morgentaler A, Traish AM. Shifting the paradigm of testosterone and prostate cancer: The saturation model and the limits of androgen-dependent growth. Eur Urol 2009;55:310-20.
34. Huhtaniemi IT, Pye SR, Limer KL, Thomson W, O'Neill TW, Platt H, Payne D, John SL, Jiang M, Boonen S, Borghs H, Vanderschueren D, Adams JE, Ward KA, Bartfai G, Casanueva F, Finn JD, Forti G, Giwercman A, Han TS, Kula K, Lean ME, Pendleton N, Punab M, Silman AJ, Wu FC. Increased estrogen rather than decreased androgen action is associated with longer androgen receptor CAG repeats. J Clin Endocrinol Metab 2009;94:277-84.
35. Hudson DL. Epithelial stem cells in human prostate growth and disease. Prostate Cancer Prostatic Dis 2004;7:188-94.
36. Lakshman KM, Kaplan B, Travison TG, Basaria S, Knapp PE, Singh AB, LaValley MP, Mazer NA, Bhasin S. The effects of injected testosterone dose and age on the conversion of testosterone to estradiol and dihydrotestosterone in young and older men. J Clin Endocrinol Metab 2010;95:3955-64.
37. Litvinov IV, De Marzo AM, Isaacs JT. Is the Achilles' heel for prostate cancer therapy a gain of function in androgen receptor signaling? J Clin Endocrinol Metab 2003;88:2972-82.
38. Prehn RT. On the prevention and therapy of prostate cancer by androgen administration. Cancer Res 1999;59:4161-4.
39. Morales A, Black AM, Emerson LE. Testosterone administration to men with testosterone deficiency syndrome after external beam radiotherapy for localized prostate cancer: Preliminary observations. BJU Int 2009;103:62-4.
40. Morales A, Black A. Testosterone deficiency syndrome and prostate cancer: Illustrative annotations for a debate. Can Urol Assoc J 2008;2:52-4.
41. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM. Testosterone therapy in men with androgen deficiency syndromes: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010;95:2536-59.
42. Bhasin S, Singh AB, Mac RP, Carter B, Lee MI, Cunningham GR. Managing the risks of prostate disease during testosterone replacement therapy in older men: Recommendations for a standardized monitoring plan. J Androl 2003;24:299-311.
43. Shabsigh R. Testosterone therapy in erectile dysfunction and hypogonadism. J Sex Med 2005;2:785-92.
44. Kaufman JM, Graydon RJ. Androgen replacement after curative radical prostatectomy for prostate cancer in hypogonadal men. J Urol 2004;172:920-2.
45. Agarwal PK, Oefelein MG. Testosterone replacement therapy after primary treatment for prostate cancer. J Urol 2005;173:533-6.
46. Khera M, Grober ED, Najari B, Colen JS, Mohamed O, Lamb DJ, Lipshultz LI. Testosterone replacement therapy following radical prostatectomy. J Sex Med 2009;6:1165-70.
47. Sarosdy MF. Testosterone replacement for hypogonadism after treatment of early prostate cancer with brachytherapy. Cancer 2007;109:536-41.
48. Isbarn H, Pinthus JH, Marks LS, Montorsi F, Morales A, Morgentaler A, Schulman C. Testosterone and prostate cancer: Revisiting old paradigms. Eur Urol 2009;56:48-56.
49. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2001;86:724-31.
50. Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Holmes JH, Dlewati A, Staley J, Santanna J, Kapoor SC, Attie MF, Haddad JG Jr, Strom BL. Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab 1999;84:1966-72.
51. Nieschlag E, Swerdloff R, Behre HM, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morley JE, Schulman C, Wang C, Weidner W, Wu FC. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, and EAU recommendations. J Androl 2006;27:135-7.