Is there a protective role of testosterone against high-grade prostate cancer? Incidence and severity of prostate cancer in 553 patients who underwent prostate biopsy: a prospective data register

References

• Lunenfeld B, Mskhalaya G, Zitzmann M, et al. Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men. Aging Male 2015;18:5–15
   PubMed Web of Science ®Google Scholar
• Behre HM, Christin-Maitre S, Morales AM, Tostain J. Transversal European survey on testosterone deficiency diagnosis. Aging Male 2012;15:69–77
   PubMed Web of Science ®Google Scholar
• Grosman H, Rosales M, Fabre B, et al. Association between testosterone levels and the metabolic syndrome in adult men. Aging Male 2014;17:161–5
   PubMed Web of Science ®Google Scholar
• Park J, Cho SY, Jeong SH, et al. Low testosterone level is an independent risk factor for high-grade prostate cancer detection at biopsy. BJU Int 2016;118:230–5
   PubMed Web of Science ®Google Scholar
• Kapoor D, Goodwin E, Channer KS, Jones TH. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol 2006;154:899–906
   PubMed Web of Science ®Google Scholar
• Yassin A, Huebler D, Saad F. Long-acting testosterone undecanoate for parenteral testosterone therapy. Therapy 2006;3:709–21
   Google Scholar
• Yassin DJ, Doros G, Hammerer PG, Yassin AA. Long-term testosterone treatment in elderly men with hypogonadism and erectile dysfunction reduces obesity parameters and improves metabolic syndrome and health-related quality of life. J Sex Med 2014;11:1567–76
   PubMed Web of Science ®Google Scholar
• Saad F, Yassin A, Haider A, et al. Elderly men over 65 years of age with late-onset hypogonadism benefit as much from testosterone treatment as do younger men. Korean J Urol 2015;56:310–17
   PubMedGoogle Scholar
• Wang C, Cunningham G, Dobs A, et al. Long-term testosterone gen (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin J Endocrinol Metab 2004;89:2085–98
   PubMed Web of Science ®Google Scholar
• Kelly DM, Jones TH. Testosterone: a vascular hormone in health and disease. J Endocrinol 2013;217:R47–71
   PubMed Web of Science ®Google Scholar
• Kelly DM, Jones TH. Testosterone: a metabolic hormone in health and disease. J Endocrinol 2013;217:R25–45
   PubMed Web of Science ®Google Scholar
• Jones TH, Saad F. The effects of testosterone on risk factors for, and the mediators of, the atherosclerotic process. Atherosclerosis 2009;207:318–27
   PubMed Web of Science ®Google Scholar
• Heufelder AE, Saad F, Bunck MC, Gooren L. Fifty-two-week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycemic control in men with newly diagnosed type 2 diabetes and subnormal plasma testosterone. J Androl 2009;30:726–33
   PubMed Web of Science ®Google Scholar
• Saad F, Gooren L, Haider A, Yassin A. An exploratory study of the effects of 12 month administration of the novel long-acting testosterone undecanoate on measures of sexual function and the metabolic syndrome. Arch Androl 2007;53:353–7
   PubMed Web of Science ®Google Scholar
• Zitzmann M, Nieschlag E. Androgen receptor gene CAG repeat length and body mass index modulate the safety of long-term intramuscular testosterone undecanoate therapy in hypogonadal men. J Clin Endocrinol Metab 2007;92:3844–53
   PubMed Web of Science ®Google Scholar
• Bassil N, Alkaade S, Morley JE. The benefits and risks of testosterone replacement therapy: a review. Ther Clin Risk Manag 2009;5:427–48
   PubMedGoogle Scholar
• Faydaci G, Bilal E, Necmettin P, et al. Baldness, benign prostate hyperplasia, prostate cancer and androgen levels. Aging Male 2008;11:189–92
   PubMed Web of Science ®Google Scholar
• García-Cruz E, Piqueras M, Huguet J, et al. Low testosterone levels are related to poor prognosis factors in men with prostate cancer prior to treatment. BJU Int 2012;110:E541–6
   PubMed Web of Science ®Google Scholar
• Grosman H, Fabre B, Lopez M, et al. Complex relationship between sex hormones, insulin resistance and leptin in men with and without prostatic disease. Aging Male 2016;19:40–5
   PubMed Web of Science ®Google Scholar
• Roddam AW, Allen NE, Appleby P, Key TJ. Endogenous hormones and prostate cancer collaborative group. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst 2008;100:170–83
   PubMed Web of Science ®Google Scholar
• Eisenberg ML, Li S, Betts P, et al. Testosterone therapy and cancer risk. BJU Int 2015;115:317–21
   PubMed Web of Science ®Google Scholar
• Porcaro AB, Petrozziello A, Ghimenton C, et al. Associations of pretreatment serum total testosterone measurements with pathology-detected Gleason score cancer. Urol Int 2014;93:269–78
   PubMed Web of Science ®Google Scholar
• Cabral PH, Iwamoto MW, Fanni VS, et al. Study of testosterone as a predictor of tumor aggressiveness in patients with prostate cancer. Int Braz J Urol 2013;39:173–81
   PubMed Web of Science ®Google Scholar
• Hoffman MA, DeWolf WC, Morgentaler A. Is low serum free testosterone a marker for high grade prostate cancer? J Urol 2000;163:824–7
   PubMed Web of Science ®Google Scholar
• Botto H, Neuzillet Y, Lebret T, et al. High incidence of predominant Gleason pattern 4 localized prostate cancer is associated with low serum testosterone. J Urol 2011;186:1400–5
   PubMed Web of Science ®Google Scholar
• Morgentaler A. Turning conventional wisdom upside-down: low serum testosterone and high-risk prostate cancer. Cancer 2011;117:3885–8
   PubMed Web of Science ®Google Scholar
• Pichon A, Neuzillet Y, Botto H, et al. Preoperative low serum testosterone is associated with high-grade prostate cancer and an increased Gleason score upgrading. Prostate Cancer Prostatic Dis 2015;18:382–7
   PubMed Web of Science ®Google Scholar
• Haider A, Zitzmann M, Doros G, et al. Incidence of prostate cancer in hypogonadal men receiving testosterone therapy: observations from 5-year median follow-up of 3 registries. J Urol 2015;193:80–6
   PubMed Web of Science ®Google Scholar
• Shoskes DA, Barazani Y, Fareed K, Sabanegh E. Jr. Outcomes of prostate biopsy in men with hypogonadism prior or during testosterone replacement therapy. Int Braz J Urol 2015;41:1167–71
   PubMed Web of Science ®Google Scholar
• Muller RL, Gerber L, Moreira DM, et al. Serum testosterone and dihydrotestosterone and prostate cancer risk in the placebo arm of the reduction by dutasteride of prostate cancer events trial. Eur Urol 2012;62:757–64
   PubMed Web of Science ®Google Scholar
• Cui Y, Zong H, Yan H, Zhang Y. The effect of testosterone replacement therapy on prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis 2014;17:132–43
   PubMed Web of Science ®Google Scholar
• Shabsigh R, Crawford ED, Nehra A, Slawin KM. Testosterone therapy in hypogonadal men and potential prostate cancer risk: a systematic review. Int J Impot Res 2009;21:9–23
   PubMed Web of Science ®Google Scholar
• Mottet N, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, diagnosis, and local treatment with curative intent. Eur Urol 2017;71:618–29
   PubMed Web of Science ®Google Scholar
• Feneley MR, Carruthers M. Is testosterone treatment good for the prostate? Study of safety during long-term treatment. J Sex Med 2012;9:2138–49
   PubMed Web of Science ®Google Scholar
• Raynaud JP. Prostate cancer risk in testosterone-treated men. J Steroid Biochem Mol Biol 2006;102:261–6
   PubMed Web of Science ®Google Scholar
• Efesoy O, Apa D, Tek M, Çayan S. The effect of testosterone treatment on prostate histology and apoptosis in men with late-onset hypogonadism. Aging Male 2016;19:79–84
   PubMed Web of Science ®Google Scholar
• Bhasin S, Cunningham G, Hayes F, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2010;95:2536–59
   PubMed Web of Science ®Google Scholar
• Huggins C, Stevens RE Jr., Hodges CV. Studies on prostatic cancer II: the effects of castration on advanced carcinoma of the prostate gland. Arch Surg 1941;43:209–23
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Hassan J, Barkin J. Testosterone deficiency syndrome: benefits, risks, and realities associated with testosterone replacement therapy. Can J Urol 2016;23:20–30
   PubMedGoogle Scholar
• Morgentaler A. Testosterone therapy for men at risk for or with history of prostate cancer. Curr Treat Options Oncol 2006;7:363–9
   PubMedGoogle Scholar
• 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;170:2348–51
   PubMed Web of Science ®Google Scholar
• Yassin A, Nettleship JE, Talib RA, et al. Effects of testosterone replacement therapy withdrawal and re-treatment in hypogonadal elderly men upon obesity, voiding function and prostate safety parameters. Aging Male 2016;19:64–9
   PubMed Web of Science ®Google Scholar
• Yassin A, Almehmadi Y, Saad F, et al. Effects of intermission and resumption of long-term testosterone replacement therapy on body weight and metabolic parameters in hypogonadal in middle-aged and elderly men. Clin Endocrinol 2016;84:107–14
   PubMed Web of Science ®Google Scholar
• Yano M, Imamoto T, Suzuki H, et al. The clinical potential of pretreatment serum testosterone level to improve the efficiency of prostate cancer screening. Eur Urol 2007;51:375–80
   PubMed Web of Science ®Google Scholar
• Sher DJ, Mantzoros C, Jacobus S, et al. Absence of relationship between steroid hormone levels and prostate cancer tumor grade. Urology 2009;73:356–61. discussion 361–2
   PubMed Web of Science ®Google Scholar
• Schatzl G, Madersbacher S, Thurridl T, et al. High-grade prostate cancer is associated with low serum testosterone levels. Prostate 2001;47:52–8
   PubMed Web of Science ®Google Scholar
• Morote J, Ramirez C, Gomez E, et al. The relationship between total and free serum testosterone and the risk of prostate cancer and tumour aggressiveness. BJU Int 2009;104:486–9
   PubMed Web of Science ®Google Scholar
• Morgentaler A, Bruning CO, III DeWolf WC. Occult prostate cancer in men with low serum testosterone levels. JAMA 1996;276:1904–6
   PubMed Web of Science ®Google Scholar
• Lane BR, Stephenson AJ, Magi-Galluzzi C, et al. Low testosterone and risk of biochemical recurrence and poorly differentiated prostate cancer at radical prostatectomy. Urology 2008;72:1240–5
   PubMed Web of Science ®Google Scholar
• Xylinas E, Ploussard G, Durand X, et al. Low pretreatment total testosterone (<3 ng/ml) predicts extraprostatic disease in prostatectomy specimens from patients with preoperative localized prostate cancer. BJU Int 2011;107:1400–3
   PubMed Web of Science ®Google Scholar
• Botelho F, Pina F, Figueiredo L, et al. Does baseline total testosterone improve the yielding of prostate cancer screening? Eur J Cancer 2012;48:1657–63
   PubMed Web of Science ®Google Scholar
• Morgentaler A, Rhoden EL. Prevalence of prostate cancer among hypogonadal men with prostate-specific antigen of 4.0 ng/ml or less. Urology 2006;68:1263–7
   PubMed Web of Science ®Google Scholar
• Shin BS, Hwang EC, Im CM, et al. Is a decreased serum testosterone level a risk factor for prostate cancer? A cohort study of Korean men. Korean J Urol 2010;51:819–23
   PubMedGoogle Scholar
• Wallis CJD, Lo K, Lee Y, et al. Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study. Lancet Diabetes Endocrinol 2016;4:498–506
   PubMed Web of Science ®Google Scholar
• Haider A, Yassin A, Haider KS, et al. Men with testosterone deficiency and a history of cardiovascular diseases benefit from long-term testosterone therapy: observational, real-life data from a registry study. Vasc Health Risk Manag 2016;12:251–61
   PubMed Web of Science ®Google Scholar
• Yassin A, Saad F. Testosterone treatment in hypogonadal patients does not cause higher incidence of prostate cancer. J Urol 2008;179:301
   Web of Science ®Google Scholar