Current Treatment Options in Oncology

, Volume 7, Issue 5, pp 363–369 | Cite as

Testosterone therapy for men at risk for or with history of prostate cancer

  • Abraham Morgentaler
Article

Opinion statement

Since the early 1940s when Huggins showed that severe reductions in serum testosterone by castration or estrogen therapy caused regression of prostate cancer (PCa), it has been assumed that higher testosterone levels cause enhanced growth of PCa. For this reason, it has been considered taboo to offer testosterone replacement therapy (TRT) to any man with a prior history of PCa, even if all objective evidence suggests he has been cured. The fear has been that higher testosterone levels would “awaken” dormant cells and cause a recurrence. Thus, US Food and Drug Administration-mandated language in all testosterone package inserts states that testosterone is contraindicated in men with a history of, or suspected of having, PCa. Although there is little modern experience with administration of testosterone in men with known history of PCa, there is a varied and extensive literature indicating that TRT does not pose any increased risk of PCa growth in men with or without prior treatment. For instance, the cancer rate in TRT trials is only approximately 1%, similar to detection rates in screening programs, yet biopsy-detectable PCa is found in one of seven hypogonadal men. Moreover, PCa is almost never seen in the peak testosterone years of the early 20s, despite autopsy evidence that men in this age group already harbor microfoci of PCa in substantial numbers. The growing number of PCa survivors who happen to be hypogonadal and request treatment has spurred a change in attitude toward this topic, with increasing numbers of physicians now offering TRT to men who appear cured of their disease. Publications have now reported no prostate-specific antigen (PSA) recurrence with TRT in small numbers of men who had undetectable PSA values after radical prostatectomy. Although still controversial, there appears to be little reason to withhold TRT from men with favorable outcomes after definitive treatment for PCa. Monitoring with PSA and digital rectal examination at regular intervals is recommended.

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References and Recommended Reading

  1. 1.
    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, 1:293–297.Google Scholar
  2. 2.
    Physician's Desk Reference. Montvale, NJ: Thomson PDR; 2005:3245.Google Scholar
  3. 3.
    Gaylis FD, Lin DW, Ignatoff JM, et al.: Prostate cancer in men using testosterone supplementation. J Urol 2005, 174:534–538.PubMedCrossRefGoogle Scholar
  4. 4.
    Rhoden EL, Morgentaler A: Risks of testosterone-replacement therapy and recommendations for monitoring. N Engl J Med 2004, 350:482–492. A major review of the risks of testosterone therapy, with emphasis on PCa.PubMedCrossRefGoogle Scholar
  5. 5.
    Gould DC, Kirby RS: Testosterone replacement therapy for late onset hypogonadism: what is the risk of inducing prostate cancer. Prostate Cancer Prostatic Dis 2006, 9:14–18.PubMedCrossRefGoogle Scholar
  6. 6.
    Bhasin S, Singh AB, Mac RP, et al.: 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. Thoughtful review of the literature, with recommendations regarding monitoring of men receiving testosterone therapy.PubMedGoogle Scholar
  7. 7.
    Morgentaler A: Testosterone replacement therapy and prostate risks: where's the beef. Can J Urol 2006, 13:S40-S43.Google Scholar
  8. 8.
    Barqawi AB, Crawford ED: Testosterone replacement therapy and the risk of prostate cancer: a perspective view. Int J Impot Res 2005, 17:462–463.PubMedCrossRefGoogle Scholar
  9. 9.
    Kaufman JM, Graydon RJ: Androgen replacement after curative radical prostatectomy for prostate cancer in hypogonadal men. J Urol 2004, 172:920–922. First paper to suggest that it may be safe to treat men with testosterone after radical prostatectomy.PubMedCrossRefGoogle Scholar
  10. 10.
    Agarwal PK, Oefelein MG: Testosterone replacement therapy after primary treatment for prostate cancer. J Urol 2005, 173:533–536.PubMedCrossRefGoogle Scholar
  11. 11.
    Prout GR, Brewer WR: Response of men with advanced prostatic carcinoma to exogenous administration of testosterone. Cancer 1967, 20:1871–1878.PubMedCrossRefGoogle Scholar
  12. 12.
    Fowler JE, Whitmore WF Jr: The response of metastatic adenocarcinoma of the prostate to exogenous testosterone. J Urol 1981, 126:372–375.PubMedGoogle Scholar
  13. 13.
    Sakr WA, Grignon DJ, Crissman JD, et al.: High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma between the ages of 20-69: an autopsy study of 249 cases. In Vivo 1994, 8:439–443.PubMedGoogle Scholar
  14. 14.
    Hsing AW: Hormones and prostate cancer: what's next. Epidemiol Rev 2001, 23:42–58.PubMedGoogle Scholar
  15. 15.
    Parsons JK, Carter HB, Platz EA, et al.: Serum testosterone and the risk of prostate cancer: potential implications for testosterone therapy. Cancer Epidemiol Biomarkers Prev 2005, 14:2257–2260.PubMedCrossRefGoogle Scholar
  16. 16.
    Statin P, Lumme S, Tenkanen L, et al.: High levels of circulating testosterone are not associated with increased prostate cancer risk: a pooled prospective study. Int J Cancer 2004, 108:418–424. Largest of the longitudinal studies, suggesting a relationship of PCa with low testosterone, rather than high testosterone.CrossRefGoogle Scholar
  17. 17.
    Chen C, Weiss NS, Stanczyk FZ, et al.: Endogenous sex hormones and prostate cancer risk: a case-control study nested within the Carotene and Retinol Efficacy Trial. Cancer Epidemiol Biomarkers Prev 2003, 12:1410–1416.PubMedGoogle Scholar
  18. 18.
    Platz EA, Leitzmann MF, Rifai N, et al.: Sex steroid hormones and the androgen receptor gene CAG repeat and subsequent risk of prostate cancer in the prostate-specific antigen era. Cancer Epidemiol Biomarkers Prev 2005, 14:1262–1269.PubMedCrossRefGoogle Scholar
  19. 19.
    Gann PH, Hennekens CH, Ma J, et al.: Prospective study of sex hormone levels and risk of prostate cancer. J Natl Cancer Inst 1996, 88:1118–1126.PubMedCrossRefGoogle Scholar
  20. 20.
    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, 170:2348–2351. Report of testosterone treatment in a group of men at high risk for developing PCa.PubMedCrossRefGoogle Scholar
  21. 21.
    Lefkowitz GK, Taneja SS, Brown J, et al.: Follow-up interval prostate biopsy 3 years after diagnosis of high grade prostatic intraepithelial neoplasia is associated with high likelihood of prostate cancer, independent of change in prostate specific antigen levels. J Urol 2002, 168:1415–1418.PubMedCrossRefGoogle Scholar
  22. 22.
    Morgentaler A, Bruning CO III, DeWolf WC: Incidence of occult prostate cancer among men with low total or free serum testosterone. JAMA 1996, 276:1904–1906.PubMedCrossRefGoogle Scholar
  23. 23.
    Thompson IM, Pauler DK, Goodman PJ, et al.: Prevalence of prostate cancer among men with a prostate-specific antigen level less than or equal to 4 ng per milliliter. N Eng J Med 2004, 350:2239–2246. This paper establishes the modern benchmark for cancer detection rates in men with normal PSA values.CrossRefGoogle Scholar
  24. 24.
    Bubley GJ: Is the flare phenomenon clinically significant. Urology 2001, 58(Suppl 2A):5–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Kuhn JM, Billebaud T, Navratil H, 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, 321:413–418.PubMedCrossRefGoogle Scholar
  26. 26.
    Tomera K, Gleason D, Gittelman 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, 16:1585–1589.Google Scholar
  27. 27.
    Sato N, Akakura K, Isaka S, et al.: Chiba Prostate Study Group. Intermittent androgen suppression for locally advanced and metastatic prostate cancer: preliminary report of a prospective multicenter study. Urology 2004, 64:341–345.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2006

Authors and Affiliations

  • Abraham Morgentaler
    • 1
  1. 1.Men's Health Boston Harvard Medical SchoolBrooklineUSA

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