Shifting the Paradigm of Testosterone and Prostate Cancer: The Saturation Model and the Limits of Androgen-Dependent Growth

European Urology

Volumn 55, Issue 2, 2009, Pages 310-321

  Morgentaler, Abraham ^a   Traish, Abdulmaged M ^b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Androgen receptor; Androgens; Hypogonadism; Prostate cancer; Saturation; Testosterone

Indexed keywords

ACYLINE; ANDROGEN; ANDROGEN RECEPTOR; BUSERELIN; DUTASTERIDE; FINASTERIDE; GONADORELIN ANTAGONIST; NAFARELIN; PLACEBO; PROSTATE SPECIFIC ANTIGEN; TESTOSTERONE; TESTOSTERONE UNDECANOATE; UNCLASSIFIED DRUG;

CANCER GROWTH; CASTRATION; DRUG EFFECT; HORMONE ACTION; HUMAN; HYPOGONADISM; NONHUMAN; PRIORITY JOURNAL; PROSTATE CANCER; PROSTATE HYPERTROPHY; RECEPTOR BINDING; REVIEW; TESTOSTERONE BLOOD LEVEL;

ANIMALS; CELL DIVISION; CELL LINE, TUMOR; HUMANS; HYPOGONADISM; MALE; ORCHIECTOMY; PROSTATE; PROSTATE-SPECIFIC ANTIGEN; PROSTATIC NEOPLASMS; RECEPTORS, ANDROGEN; TESTOSTERONE;

EID: 57649176913     PISSN: 03022838     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.eururo.2008.09.024     Document Type: Review

References (49)

1. Huggins C., and Hodges C.V. 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 1 (1941) 293-297
2. Huggins C., Stevens Jr. R.E., and Hodges C.V. Studies on prostatic cancer. II. The effects of castration on advanced carcinoma of the prostate gland. Arch Surg 43 (1941) 209-223
3. Roddam A.W., Allen N.E., Appleby P., et al., Endogenous Hormones Prostate Cancer Collaborative Group. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. JNCI 100 (2008) 170-183
4. Morgentaler A. Testosterone and prostate cancer: an historical perspective on a modern myth. Eur Urol 50 (2006) 935-939
5. Carpenter W.R., Robinson W., and Godley P.A. Getting over testosterone: postulating a fresh start for etiologic studies of prostate cancer. JNCI 100 (2008) 158-159
6. Wang C., Cunningham G., Dobs A., 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 89 (2004) 2085-2098
7. Morgentaler A. Testosterone replacement therapy and prostate cancer. Urol Clin North Am 34 (2007) 555-563
8. Traish A.M., Williams D.F., Hoffman N.D., and Wotan H.H. Validation of the exchange assay for the measurement of androgen receptors in human and dog prostates. Prog Clin Biol Res 262 (1988) 145-160
9. Ho S.M., Damassa D., Kwan P.W., Seto H.S., and Leav I. Androgen receptor levels and androgen contents in the prostate lobes of intact and testosterone-treated Noble rats. J Androl 6 (1985) 279-290
10. Anderson J.N., Peck Jr. E.J., and Clark J.H. Nuclear receptor estrogen complex: relationship between concentration and early uterotrophic responses. Endocrinology 93 (1973) 711-717
11. Farman N., Kusch M., and Edelman I.S. Aldosterone receptor occupancy and sodium transport in the urinary bladder of Bufo marinus. Am J Physiol 235 (1978) C90-C96
12. Wright A.S., Douglas R.C., Thomas L.N., Lazier C.B., and Rittmaster R.S. Androgen-induced regrowth in the castrated rat ventral prostate: role of 5α-reductase. Endocrinology 140 (1999) 4509-4515
13. Robaire B., Ewing L.L., Irby D.C., and Desjardins C. Interactions of testosterone and estradiol-17 beta on the reproductive tract of the male rat. Biol Reprod 21 (1979) 455-463
14. Banerjee P.P., Banerjee S., Dorsey R., Zirkin B.R., and Brown T.R. Age- and lobe-specific responses of the brown Norway rat prostate to androgen. Biol Reprod 51 (1994) 675-684
15. Berry S.J., and Isaacs J.T. Comparative aspects of prostatic growth and androgen metabolism with aging in the dog versus the rat. Endocrinology 114 (1984) 511-520
16. Bologna M., Muzi P., Biordi L., Festuccia C., and Vicentini C. Finasteride dose-dependently reduces the proliferation rate of the LnCap human prostatic cancer cell line in vitro. Urology 45 (1995) 282-290
17. Arnold J.T., Le H., McFann K.K., and Blackman M.R. Comparative effects of DHEA versus testosterone, dihydrotestosterone, and estradiol on proliferation and gene expression in human LNCaP prostate cancer cells. Am J Physiol Endocrinol Metab 288 (2005) E573-E584
18. Bhasin S., Cunningham G.R., Hayes F.J., et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 91 (2006) 1995-2010
19. Weber J.P., Oesterling J.E., Peters C.A., Partin A.W., Chan D.W., and Walsh P.C. The influence of reversible androgen deprivation on serum prostate-specific antigen levels in men with benign prostatic hyperplasia. J Urol 141 (1989) 987-992
20. Page S.T., Lin D.W., Mostaghel E.A., et al. Persistent intraprostatic androgen concentrations after medical castration in healthy men. J Clin Endocrinol Metab 91 (2006) 3850-3856
21. Marks L.S., Andriole G.L., Fitzpatrick J.M., Schulman C.C., and Roehrborn C.G. The interpretation of serum prostate specific antigen in men receiving 5α-reductase inhibitors: a review and clinical recommendations. J Urol 176 (2006) 868-874
22. Monath J.R., McCullough D.L., Hart L.J., and Jarow J.P. Physiologic variations of serum testosterone within the normal range do not affect serum prostate-specific antigen. Urology 46 (1995) 58-61
23. Mohr B.A., Feldman H.A., Kalish L.A., Longcope C., and McKinlay J.B. Are serum hormones associated with the risk of prostate cancer? Prospective results from the Massachusetts Male Aging Study. Urology 57 (2001) 930-935
24. Cooper C.S., Perry P.J., Sparks A.E., MacIndoe J.H., Yates W.R., and Williams R.D. Effect of exogenous testosterone on prostate volume, serum and semen prostate specific antigen levels in healthy young men. J Urol 159 (1998) 441-443
25. Bhasin S., Storer T.W., Berman N., et al. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med 335 (1996) 1-7
26. Nair K.S., Rizza R.A., O'Briend P., et al. DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med 355 (2006) 1647-1659
27. Emmelot-Vonk M.H., Verhaar H.J., Nakhai Pour H.R., et al. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. JAMA 299 (2008) 39-52
28. Bhasin S., Woodhouse L., Casaburi R., et al. Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab 281 (2001) E1172-E1181
29. Bhasin S., Woodhouse L., Casaburi R., et al. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J Clin Endocrinol Metab 90 (2005) 678-688
30. Steidle C., Schwartz S., Jacoby K., Sebree T., Smith T., Bachand R., and North American AA2500 T Gel Study Group. AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J Clin Endocrinol Metab 88 (2003) 2673-2681
31. Calof O.M., Singh A.B., Lee M.L., 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 60 (2005) 1451-1457
32. Dean J.D., Carnegie C., Rodzvilla J., and Smith T. Long-term effects of testim(r) 1% testosterone gel in hypogonadal men. Rev Urol 7 (2005) 87-94
33. D'Amico A.V., and Roehrborn C.G. Effect of 1 mg/d finasteride on concentrations of serum prostate-specific antigen in men with androgenic alopecia: a randomised controlled trial. Lancet Oncol 8 (2007) 21-25
34. Rhoden E.L., and Morgentaler A. Influence of demographic factors and biochemical characteristics on the prostate-specific antigen (PSA) response to testosterone replacement therapy. Int J Impot Res 18 (2006) 201-205
35. Rhoden E.L., and Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. N Engl J Med 350 (2004) 482-492
36. Kuhn J.M., 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 321 (1989) 413-418
37. McLeod D., Zinner N., Tomera K., et al., Abarelix Study Group. A phase 3, multicenter, open-label, randomized study of abarelix versus leuprolide acetate in men with prostate cancer. Urology 58 (2001) 756-761
38. 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 16 (2001) 1585-1589
39. Fowler J.E., and Whitmore Jr. W.F. The response of metastatic adenocarcinoma of the prostate to exogenous testosterone. J Urol 126 (1981) 372-375
40. Prout G.R., and Brewer W.R. Response of men with advanced prostatic carcinoma to exogenous administration of testosterone. Cancer 20 (1967) 1871-1878
41. Morgentaler A. Testosterone deficiency and prostate cancer: emerging recognition of an important and troubling relationship. Eur Urol 52 (2007) 623-625
42. Morgentaler A., Bruning III C.O., and DeWolf W.C. Incidence of occult prostate cancer among men with low total or free serum testosterone. JAMA 276 (1996) 1904-1906
43. Morgentaler A., and Rhoden E.L. Prevalence of prostate cancer among hypogonadal men with prostate-specific antigen of 4.0 ng/ml or less. Urology 68 (2006) 1263-1267
44. Marberger M., Roehrborn C.G., Marks L.S., Wilson T., and Rittmaster R.S. Relationship among serum testosterone, sexual function, and response to treatment in men receiving dutasteride for benign prostatic hyperplasia. J Clin Endocrinol Metab 91 (2006) 1323-1328
45. Ho S., Damassa D., Kwan P.W.L., Seto H.S.K., and Leav I. Androgen receptor levels and androgen contents in the prostate lobes of intact and testosterone-treated Noble rats. J Androl 6 (1985) 279-290
46. Traish A.M., Muller R.E., and Wotiz H.H. A new procedure for the quantitation of nuclear and cytoplasmic androgen receptors. J Biol Chem 256 (1981) 12028-12033
47. Marks L.S., Mazer N.A., Mostaghel E., et al. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. JAMA 296 (2006) 2351-2361
48. Sakr W.A., Grignon D.J., Crissman J.D., 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 8 (1994) 439-443
49. Thompson I.M., Goodman P.J., Tangen C.M., et al. The influence of finasteride on the development of prostate cancer. N Engl J Med 349 (2003) 215-224