Best Practice & Research Clinical Endocrinology & Metabolism
Volume 22, Issue 4 , Pages 601-613 , August 2008

Androgens and prostate cancer risk

  • Pär Stattin, MD, PhD (Consultant in Urology, Associate Professor)

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +46 90 785 22 91; Fax: +46 90 12 53 96.

References 

  1. Bosland MC. The role of steroid hormones in prostate carcinogenesis. Journal of the National Cancer Institute. Monographs. 2000;(27):39–66
  2. Hsing AW, Reichardt JK, Stanczyk FZ. Hormones and prostate cancer: current perspectives and future directions. Prostate. 2002 Aug 1;52(3):213–235
  3. Platz EA, Giovannucci E. The epidemiology of sex steroid hormones and their signaling and metabolic pathways in the etiology of prostate cancer. The Journal of Steroid Biochemistry and Molecular Biology. 2004 Nov;92(4):237–253
  4. Bladou F, Vessella RL, Buhler KR, et al. Cell proliferation and apoptosis during prostatic tumor xenograft involution and regrowth after castration. International Journal of Cancer. 1996 Sep 17;67(6):785–790
  5. Lucia MS, Bostwick DG, Bosland M, et al. Workgroup I: rodent models of prostate cancer. Prostate. 1998 Jun 15;36(1):49–55
  6. Noble RL. The development of prostatic adenocarcinoma in Nb rats following prolonged sex hormone administration. Cancer Research. 1977 Jun;37(6):1929–1933
  7. Bostwick DG, Burke HB, Djakiew D, et al. Human prostate cancer risk factors. Cancer. 2004 Nov 15;101(Suppl. 10):2371–2490
  8. Keller ET, Ershler WB, Chang C. The androgen receptor: a mediator of diverse responses. Frontiers in Bioscience: A Journal and Virtual Library. 1996 Mar 1;1:d59–d71
  9. Kaarbo M, Klokk TI, Saatcioglu F. Androgen signaling and its interactions with other signaling pathways in prostate cancer. BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology. 2007 Dec;29(12):1227–1238
  10. Zhou ZX, Lane MV, Kemppainen JA, et al. Specificity of ligand-dependent androgen receptor stabilization: receptor domain interactions influence ligand dissociation and receptor stability. Molecular Endocrinology. 1995 Feb;9(2):208–218
  11. Gao W, Bohl CE, Dalton JT. Chemistry and structural biology of androgen receptor. Chemical Reviews. 2005 Sep;105(9):3352–3370
  12. Russell DW, Wilson JD. Steroid 5 alpha-reductase: two genes/two enzymes. Annual Review of Biochemistry. 1994;63:25–61
  13. Amory JK, Wang C, Swerdloff RS, et al. The effect of 5alpha-reductase inhibition with dutasteride and finasteride on semen parameters and serum hormones in healthy men. The Journal of Clinical Endocrinology and Metabolism. 2007 May;92(5):1659–1665
  14. Rittmaster RS, Zwicker H, Thompson DL, et al. Androstanediol glucuronide production in human liver, prostate, and skin. Evidence for the importance of the liver in 5 alpha-reduced androgen metabolism. The Journal of Clinical Endocrinology and Metabolism. 1993 Apr;76(4):977–982
  15. Norman RW, Coakes KE, Wright AS, et al. Androgen metabolism in men receiving finasteride before prostatectomy. The Journal of Urology. 1993 Nov;150(5 Pt 2):1736–1739
  16. Nomura A, Heilbrun LK, Stemmermann GN, et al. Prediagnostic serum hormones and the risk of prostate cancer. Cancer Research. 1988 Jun 15;48(12):3515–3517
  17. Nomura AM, Stemmermann GN, Chyou PH, et al. Serum androgens and prostate cancer. Cancer Epidemiology, Biomarkers & Prevention. 1996 Aug;5(8):621–625
  18. Barrett-Connor E, Garland C, McPhillips JB, et al. A prospective, population-based study of androstenedione, estrogens, and prostatic cancer. Cancer Research. 1990 Jan 1;50(1):169–173
  19. Hsing AW, Comstock GW. Serological precursors of cancer: serum hormones and risk of subsequent prostate cancer. Cancer Epidemiology, Biomarkers & Prevention. 1993 Jan–Feb;2(1):27–32
  20. Carter HB, Pearson JD, Metter EJ, et al. Longitudinal evaluation of serum androgen levels in men with and without prostate cancer. Prostate. 1995 Jul;27(1):25–31
  21. Gann PH, Hennekens CH, Ma J, et al. Prospective study of sex hormone levels and risk of prostate cancer. Journal of the National Cancer Institute. 1996 Aug 21;88(16):1118–1126
  22. Guess HA, Friedman GD, Sadler MC, et al. 5 alpha-reductase activity and prostate cancer: a case-control study using stored sera. Cancer Epidemiology, Biomarkers & Prevention. 1997 Jan;6(1):21–24
  23. Vatten LJ, Ursin G, Ross RK, et al. Androgens in serum and the risk of prostate cancer: a nested case-control study from the Janus serum bank in Norway. Cancer Epidemiology, Biomarkers & Prevention. 1997 Nov;6(11):967–969
  24. Dorgan JF, Albanes D, Virtamo J, et al. Relationships of serum androgens and estrogens to prostate cancer risk: results from a prospective study in Finland. Cancer Epidemiology, Biomarkers & Prevention. 1998 Dec;7(12):1069–1074
  25. Heikkila R, Aho K, Heliovaara M, et al. Serum testosterone and sex hormone-binding globulin concentrations and the risk of prostate carcinoma: a longitudinal study. Cancer. 1999 Jul 15;86(2):312–315
  26. Mohr BA, Feldman HA, Kalish LA, et al. Are serum hormones associated with the risk of prostate cancer? Prospective results from the Massachusetts Male Aging Study. Urology. 2001 May;57(5):930–935
  27. Stattin P, Lumme S, Tenkanen L, et al. High levels of circulating testosterone are not associated with increased prostate cancer risk: a pooled prospective study. International Journal of Cancer. 2004 Jan 20;108(3):418–424
  28. 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 Epidemiology, Biomarkers & Prevention. 2003 Dec;12(12):1410–1416
  29. Ozasa K, Nakao M, Watanabe Y, et al. Serum phytoestrogens and prostate cancer risk in a nested case-control study among Japanese men. Cancer Science. 2004 Jan;95(1):65–71
  30. 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 Epidemiology, Biomarkers & Prevention. 2005 May;14(5):1262–1269
  31. Parsons JK, Carter HB, Platz EA, et al. Serum testosterone and the risk of prostate cancer: potential implications for testosterone therapy. Cancer Epidemiology, Biomarkers & Prevention. 2005 Sep;14(9):2257–2260
  32. Severi G, Morris HA, MacInnis RJ, et al. Circulating steroid hormones and the risk of prostate cancer. Cancer Epidemiology, Biomarkers & Prevention. 2006 Jan;15(1):86–91
  33. Travis RC, Key TJ, Allen NE, et al. Serum androgens and prostate cancer among 643 cases and 643 controls in the European Prospective Investigation into Cancer and Nutrition. International Journal of Cancer. 2007 Sep 15;121(6):1331–1338
  34. Weiss JM, Huang WY, Rinaldi S, et al. Endogenous sex hormones and the risk of prostate cancer: a prospective study. International Journal of Cancer, in press.
  35. Wiren S, Stocks T, Rinaldi S, et al. Androgens and prostate cancer risk: a prospective study. Prostate. 2007 Aug 1;67(11):1230–1237
  36. Roddam AW, Allen NE, Appleby P, et al. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. Journal of the National Cancer Institute. 2008 Feb 6;100(3):170–183
  37. Kaaks R, Lukanova A, Rinaldi S, et al. Interrelationships between plasma testosterone, SHBG, IGF-I, insulin and leptin in prostate cancer cases and controls. European Journal of Cancer Prevention. 2003 Aug;12(4):309–315
  38. MacInnis RJ, English DR. Body size and composition and prostate cancer risk: systematic review and meta-regression analysis. Cancer Causes Control. 2006 Oct;17(8):989–1003
  39. Hsing AW, Sakoda LC, Chua S. Obesity, metabolic syndrome, and prostate cancer. The American Journal of Clinical Nutrition. 2007 Sep;86(3):s843–s857
  40. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nature Reviews. Cancer. 2004 Aug;4(8):579–591
  41. Allen NE, Appleby PN, Davey GK, et al. Lifestyle and nutritional determinants of bioavailable androgens and related hormones in British men. Cancer Causes Control. 2002 May;13(4):353–363
  42. Hoffman MA, DeWolf WC, Morgentaler A. Is low serum free testosterone a marker for high grade prostate cancer?. Journal of Urology. 2000 Mar;163(3):824–827
  43. Schatzl G, Madersbacher S, Thurridl T, et al. High-grade prostate cancer is associated with low serum testosterone levels. Prostate. 2001 Apr;47(1):52–58
  44. Giwercman A, Richiardi L, Kaijser M, et al. Reduced risk of prostate cancer in men who are childless as compared to those who have fathered a child: a population based case-control study. International Journal of Cancer. 2005 Jul 20;115(6):994–997
  45. Jorgensen KT, Pedersen BV, Johansen C, et al. Fatherhood status and prostate cancer risk. Cancer. 2008 Feb 15;112(4):919–923
  46. Miller LR, Partin AW, Chan DW, et al. Influence of radical prostatectomy on serum hormone levels. Journal of Urology. 1998 Aug;160(2):449–453
  47. Madersbacher S, Schatzl G, Bieglmayer C, et al. Impact of radical prostatectomy and TURP on the hypothalamic-pituitary-gonadal hormone axis. Urology. 2002 Nov;60(5):869–874
  48. Crawford ED, Barqawi AB, O'Donnell C, et al. The association of time of day and serum testosterone concentration in a large screening population. BJU International. 2007 Sep;100(3):509–513
  49. Harman SM, Metter EJ, Tobin JD, et al. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. The Journal of Clinical Endocrinology and Metabolism. 2001 Feb;86(2):724–731
  50. Vermeulen A, Verdonck G. Representativeness of a single point plasma testosterone level for the long term hormonal milieu in men. The Journal of Clinical Endocrinology and Metabolism. 1992 Apr;74(4):939–942
  51. Anderson PH, Fukushima K, Schiller HS. Radioimmunoassay of plasma testosterone, with use of polyethylene glycol to separate antibody-bound and free hormone. Clinical Chemistry. 1975 May;21(6):708–714
  52. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. The Journal of Clinical Endocrinology and Metabolism. 1999 Oct;84(10):3666–3672
  53. Giton F, Fiet J, Guechot J, et al. Serum bioavailable testosterone: assayed or calculated?. Clinical Chemistry. 2006 Mar;52(3):474–481
  54. Key TJ, Appleby PN, Reeves GK, et al. Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. Journal of the National Cancer Institute. 2003 Aug 20;95(16):1218–1226
  55. Ebrahim S, Davey Smith G. Mendelian randomization: can genetic epidemiology help redress the failures of observational epidemiology?. Human Genetics. 2008 Feb;123(1):15–33
  56. Lindstrom S, Zheng SL, Wiklund F, et al. Systematic replication study of reported genetic associations in prostate cancer: Strong support for genetic variation in the androgen pathway. Prostate. 2006 Dec 1;66(16):1729–1743
  57. Chamberlain NL, Driver ED, Miesfeld RL. The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Research. 1994 Aug 11;22(15):3181–3186
  58. Lindstrom S, Adami HO, Balter KA, et al. Inherited variation in hormone-regulating genes and prostate cancer survival. Clinical Cancer Research. 2007 Sep 1;13(17):5156–5161
  59. Chokkalingam AP, Stanczyk FZ, Reichardt JK, et al. Molecular epidemiology of prostate cancer: hormone-related genetic loci. Frontiers in Bioscience: A Journal and Virtual Library. 2007;12:3436–3460
  60. Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. The New England Journal of Medicine. 2003 Jul 17;349(3):215–224
  61. Thompson IM, Chi C, Ankerst DP, et al. Effect of finasteride on the sensitivity of PSA for detecting prostate cancer. Journal of the National Cancer Institute. 2006 Aug 16;98(16):1128–1133
  62. Thompson IM, Lucia MS, Redman MW, et al. Finasteride decreases the risk of prostatic intraepithelial neoplasia. Journal of Urology. 2007 Jul;178(1):107–109discussion 10
  63. Thompson IM, Klein EA, Lippman SM, et al. Prevention of prostate cancer with finasteride: US/European perspective. European Urology. 2003 Dec;44(6):650–655
  64. Cohen YC, Liu KS, Heyden NL, et al. Detection bias due to the effect of finasteride on prostate volume: a modeling approach for analysis of the Prostate Cancer Prevention Trial. Journal of the National Cancer Institute. 2007 Sep 19;99(18):1366–1374
  65. Lucia MS, Epstein JI, Goodman PJ, et al. Finasteride and high-grade prostate cancer in the Prostate Cancer Prevention Trial. Journal of the National Cancer Institute. 2007 Sep 19;99(18):1375–1383
  66. Thomas LN, Douglas RC, Lazier CB, et al. Levels of 5alpha-reductase type 1 and type 2 are increased in localized high grade compared to low grade prostate cancer. Journal of Urology. 2008 Jan;179(1):147–151
  67. Andriole G, Bostwick D, Brawley O, et al. Chemoprevention of prostate cancer in men at high risk: rationale and design of the reduction by dutasteride of prostate cancer events (REDUCE) trial. Journal of Urology. 2004 Oct;172(4 Pt 1):1314–1317
  68. Nieschlag E, Swerdloff R, Behre HM, et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, and EAU recommendations. Journal of Andrology. 2006 Mar–Apr;27(2):135–137
  69. Miner MM, Seftel AD. Testosterone and ageing: what have we learned since the Institute of Medicine report and what lies ahead?. International Journal of Clinical Practice. 2007 Apr;61(4):622–632
  70. Emmelot-Vonk MH, Verhaar HJ, Nakhai Pour HR, et al. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. JAMA. 2008 Jan 2;299(1):39–52
  71. Morgentaler A, Rhoden EL. Prevalence of prostate cancer among hypogonadal men with prostate-specific antigen levels of 4.0 ng/mL or less. Urology. 2006 Dec;68(6):1263–1267
  72. Brand TC, Canby-Hagino E, Thompson IM. Testosterone replacement therapy and prostate cancer: a word of caution. Current Urology Reports. 2007 May;8(3):185–189
  73. Hwang JJ, Dharmawardana PG, Uchio EM, et al. Prostate cancer in Klinefelter syndrome during hormonal replacement therapy. Urology. 2003 Nov;62(5):941
  74. Bydder SA, Joseph DJ, Weinstein S, et al. Prostate cancer following testosterone replacement in Klinefelter syndrome. ANZ Journal of Surgery. 2007 Jan–Feb;77(1–2):93–94
  75. Swerdlow AJ, Schoemaker MJ, Higgins CD, et al. Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study. Journal of the National Cancer Institute. 2005 Aug 17;97(16):1204–1210
  76. Rhoden EL, Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. The New England Journal of Medicine. 2004 Jan 29;350(5):482–492
  77. Gould DC, Feneley MR, Kirby RS. Prostate-specific antigen testing in hypogonadism: implications for the safety of testosterone-replacement therapy. BJU International. 2006 Jul;98(1):1–4
  78. Bostwick DG, Pacelli A, Lopez-Beltran A. Molecular biology of prostatic intraepithelial neoplasia. Prostate. 1996 Aug;29(2):117–134
  79. 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. Journal of Urology. 2003 Dec;170(6 Pt 1):2348–2351
  80. Raynaud JP, Legros JJ, Rollet J, et al. Efficacy and safety of a new testosterone-in-adhesive matrix patch applied every 2 days for 1 year to hypogonadal men. The Journal of Steroid Biochemistry and Molecular Biology. 2008;109(1–2):168–176
  81. Behre HM, Bohmeyer J, Nieschlag E. Prostate volume in testosterone-treated and untreated hypogonadal men in comparison to age-matched normal controls. Clinical Endocrinology. 1994 Mar;40(3):341–349
  82. Marks LS, Mazer NA, Mostaghel E, et al. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. JAMA. 2006 Nov 15;296(19):2351–2361

PII: S1521-690X(08)00077-8

doi: 10.1016/j.beem.2008.06.002

Best Practice & Research Clinical Endocrinology & Metabolism
Volume 22, Issue 4 , Pages 601-613 , August 2008