The Journal of Urology
Volume 181, Issue 3 , Pages 972-979 , March 2009

Testosterone Therapy in Men With Prostate Cancer: Scientific and Ethical Considerations

  • Abraham Morgentaler

      Affiliations

    • Corresponding Author InformationCorrespondence: One Brookline Place, Suite #624, Brookline, Massachusetts 02445 (telephone: 617-277-5000; FAX: 617-277-5444)
    • Financial interest and/or other relationship with Auxilium, Solvay, Indevus, Slate, Watson and Bayer.

Received 27 August 2008

References 

  1. Morgentaler A. Testosterone replacement therapy and prostate cancer. Urol Clin North Am. 2007;34:555
  2. Rhoden EL, Averback MA, Teloken PE. Androgen replacement in men undergoing treatment for prostate cancer. J Sex Med. 2008;5:2202
  3. Morgentaler A. Testosterone and prostate cancer: an historical perspective on a modern myth. Eur Urol. 2006;50:935
  4. Kaufman JM, Graydon RJ. Androgen replacement after curative radical prostatectomy for prostate cancer in hypogonadal men. J Urol. 2004;172:920
  5. Agarwal PK, Oefelein MG. Testosterone replacement therapy after primary treatment for prostate cancer. J Urol. 2005;173:533
  6. Sarosdy MF. Testosterone replacement for hypogonadism after treatment of early prostate cancer with brachytherapy. Cancer. 2007;109:536
  7. Morgentaler A: Two years of testosterone therapy associated with decline in serum prostate-specific antigen in a man with untreated prostate cancer. Unpublished data.
  8. Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, et al. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone density in hypogonadal men. J Clin Endocrinol Metab. 2004;89:2085
  9. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2006;91:1995
  10. Morgentaler A. Guilt by association: a historical perspective on Huggins, testosterone therapy, and prostate cancer. J Sex Med. 2008;5:1834
  11. 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
  12. Prout GR, Brewer WR. Response of men with advanced prostatic carcinoma to exogenous administration of testosterone. Cancer. 1967;20:1871
  13. Fowler JE, Whitmore WF. The response of metastatic adenocarcinoma of the prostate to exogenous testosterone. J Urol. 1981;126:372
  14. Bubley GJ. Is the flare phenomenon clinically significant?. Urology. 2001;58(suppl.):5
  15. Liverman CT, Blazer DG. Testosterone and Aging: Clinical Research Directions. Washington D. C: National Academies Press; 2004;
  16. Rhoden EL, Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. N Engl J Med. 2004;350:482
  17. Tindall DJ, Rittmaster RS. The rationale for inhibiting 5alpha-reductase isoenzymes in the prevention and treatment of prostate cancer. J Urol. 2008;179:1235
  18. Morgentaler A, Traish AM. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen stimulation of prostate cancer. Eur Urol. 2008;Epub ahead of print.
  19. Traish AM, Williams DF, Hoffman ND, Wotan HH. Validation of the exchange assay for the measurement of androgen receptors in human and dog prostates. Prog Clin Biol Res. 1988;262:145
  20. Ho SM, Damassa D, Kwan PW, Seto HS, Leav I. Androgen receptor levels and androgen contents in the prostate lobes of intact and testosterone-treated Noble rats. J Androl. 1985;6:279
  21. Bologna M, Muzi P, Biordi L, Festuccia C, Vicentini C. Finasteride dose-dependently reduces the proliferation rate of the LnCap human prostatic cancer cell line in vitro. Urology. 1995;45:282
  22. 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
  23. Kuhn JM, Billebaud T, Navratil H, Moulonguet A, Fiet J, Grise P, et al. Prevention of the transient adverse effects of a gonadotropin-releasing hormone analogue (buserelin) in metastatic prostatic carcinoma by administration of an antiandrogen (nilutamide). N Engl J Med. 1989;321:413
  24. Tomera K, Gleason D, Gittelman M, Moseley W, Zinner N, Murdoch M, et al. The gonadotropin-releasing hormone antagonist abarelix depot versus luteinizing hormone releasing hormone agonists leuprolide or goserelin: initial results of endocrinological and biochemical efficacies in patients with prostate cancer. J Urol. 2001;165:1585
  25. 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
  26. Marks LS, Andriole GL, Fitzpatrick JM, Schulman CC, Roehrborn CG. The interpretation of serum prostate specific antigen in men receiving 5alpha-reductase inhibitors: a review and clinical recommendations. J Urol. 2006;176:868
  27. Monath JR, McCullough DL, Hart LJ, Jarow JP. Physiologic variations of serum testosterone within the normal range do not affect serum prostate-specific antigen. Urology. 1995;46:58
  28. Mohr BA, Feldman HA, Kalish LA, Longcope C, McKinlay JB. Are serum hormones associated with the risk of prostate cancer? (Prospective results from the Massachusetts Male Aging Study). Urology. 2001;57:930
  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
  30. Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, et al. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med. 1996;335:1
  31. Steidle C, Schwartz S, Jacoby K, Sebree T, Smith T, Bachand R, et al. AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J Clin Endocrinol Metab. 2003;88:2673
  32. Calof OM, Singh AB, Lee ML, Kenny AM, Urban RJ, Tenover JL, et al. Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci. 2005;60:1451
  33. Rhoden EL, Morgentaler A. Influence of demographic factors and biochemical characteristics on the prostate-specific antigen (PSA) response to testosterone replacement therapy. Int J Impot Res. 2006;18:201
  34. Parsons JK, Carter HB, Platz EA, Wright EJ, Landis P, Metter EJ. Serum testosterone and the risk of prostate cancer: potential implications for testosterone therapy. Cancer Epidemiol Biomarkers Prev. 2005;14:2257
  35. Roddam AW, Allen NE, Appleby P, Key TJ Endogenous Hormones Prostate Cancer Collaborative Group. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst. 2008;100:170
  36. Morgentaler A. Testosterone deficiency and prostate cancer: emerging recognition of an important and troubling relationship. Eur Urol. 2007;52:623
  37. Yamamoto S, Yonese J, Kawakami S, Ohkubo Y, Tatokoro M, Komai Y, et al. Preoperative serum testosterone level as an independent predictor of treatment failure following radical prostatectomy. Eur Urol. 2007;52:696
  38. Khera M, Colen J, Grober E, Najari BB, Murthy L, Lamb DJ, et al. The safety and efficacy of testosterone replacement therapy following radical prostatectomy. J Urol. 2007;177(suppl.):384;abstract 1164
  39. Nabulsi O, Tal R, Gotto G, Narus J, Goldenberg L, Mulhall JP. Outcomes analysis of testosterone supplementation in hypogonadal men following radical prostatectomy. J Urol. 2008;179(suppl.):406;abstract 1181
  40. Davila HH, Arison CN, Hall MK, Salup R, Lockhart JL, Carrion RE. Analysis of the PSA response after testosterone supplementation in patients who have previously received management for their localized prostate cancer. J Urol. 2008;179(suppl.):428;abstract 1247
  41. Sasagawa I, Nakada T, Kubota Y, Sawamura T, Izumiya K. Changes in serum levels of prostatic acid phosphatase and prostate specific antigen after luteinizing hormone-releasing hormone analogue administration in patients with metastatic prostatic cancer in relation to glandular differentiation. Int Urol Nephrol. 1995;27:769
  42. Morgentaler A, Rhoden EL. Prevalence of prostate cancer among hypogonadal men with prostate-specific antigen of 4.0 ng/ml or less. Urology. 2006;68:1263
  43. Marks LS, Mazer NA, Mostaghel E, Hess DL, Dorey FJ, Epstein JI, et al. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. JAMA. 2006;296:2351
  44. van Oort IM, Kok DE, Kiemeney LA, Hulsbergen-van de Kaa CA, Witjes JA. A single institution experience with biochemical recurrence after radical prostatectomy for tumors that on pathology are of small volume or “insignificant.”. Urol Oncol. 2008;Epub ahead of print.
  45. Rhoden EL, Morgentaler A. Testosterone replacement therapy in hypogonadal men at high risk for prostate cancer: results of 1 year of treatment in men with prostatic intraepithelial neoplasia. J Urol. 2003;170:2348
  46. Morgentaler A, Bruning CO, DeWolf WC. Incidence of occult prostate cancer among men with low total or free serum testosterone. JAMA. 1996;276:1904
  47. Chuu CP, Hiipakka RA, Fukuchi J, Kokontis JM, Liao S. Androgen causes growth suppression and reversion of androgen-independent prostate cancer xenografts to an androgen-stimulated phenotype in athymic mice. Cancer Res. 2005;65:2082
  48. Svatek RS, Shulman MJ, Benaim EA, Rogers TE, Margulis V. Change in prostate specific antigen following androgen stimulation is an independent predictor of prostate cancer diagnosis. J Urol. 2008;179:2192
  49. Gaylis FD, Lin DW, Ignatoff JM, Amling CL, Tutrone RF, Cosgrove DJ. Prostate cancer in men using testosterone supplementation. J Urol. 2005;174:534
  50. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349:215

 Editor's Note: This article is the first of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 1510 and 1511.

PII: S0022-5347(08)03058-9

doi: 10.1016/j.juro.2008.11.031

The Journal of Urology
Volume 181, Issue 3 , Pages 972-979 , March 2009

Article Tools

* Image Usage & Resolution