Clinically occult prostate cancer cases may distort the effect of testosterone replacement therapy on risk of PCa

  • Xiao Zhang
  • Yan Zhong
  • Farid Saad
  • Karim Haider
  • Ahmad Haider
  • Xiaohui XuEmail author
Original Article



Although prostate cancer (PCa) screening is conducted before testosterone replacement therapy (TRT), clinically occult PCa cases may exist.


To evaluate whether the possible inclusion of occult PCa cases distorts the effect of TRT on risk of PCa, we followed 776 hypogonadal males (TRT = 400, non-TRT = 376) from a urology center in Germany from 2004 to 2016, with a mean follow-up period of 7 years. We assumed occult cases might take 1–2 years (latency period) to become clinically detectable after receiving TRT. We selected several latency periods (12/18/24 months) and compared the risk of PCa in the TRT and non-TRT group over the latency period, from the end of latency period till the end of follow-up, and over the whole follow-up time.


Overall, 26 PCa cases occurred in the non-TRT group vs 9 cases in the TRT group. Within 18 months of follow-up, 9 cases occurred in the TRT group vs 0 cases in the non-TRT group; from the end of 18 months till the end of follow-up, 26 cases occurred in the non-TRT group vs 0 cases in the TRT group. The adjusted table showed seemingly adverse effects of TRT on PCa development within 18 months (p = 0.0301) and beneficial effects from the end of 18 months till the end of follow-up (p = 0.0069). Similar patterns were observed for 12 or 24 months as the latency period.


TRT may make occult PCa cases detectable within early phase of treatment and present a beneficial effect in the long run. Future longitudinal studies are needed to confirm findings from our exploratory analyses.


Longitudinal study Prostate cancer Testosterone replacement therapy Undetected cases Prostate-specific antigen 


Author contribution

XZ: project development, manuscript writing. YZ: project development, data analysis. FS: manuscript editing. KH: data collection and management. AH: data collection and management. XX: project development, manuscript editing.

Compliance with ethical standards

Conflict of interest

Dr. Farid Saad has a financial relationship with Bayer AG.

Animal and human participants

The project involved human subjects. All human subjects provided written informed consent with guarantee of confidentiality. IRB approved the study protocol.


  1. 1.
    Raynaud JP (2006) Prostate cancer risk in testosterone-treated men. J Steroid Biochem Mol Biol 102:261–266. Accessed 18 May 2017
  2. 2.
    Isidori AM, Buvat J, Corona G, et al (2014) A critical analysis of the role of testosterone in erectile function: from pathophysiology to treatment-a systematic review. Eur Urol 65:99–112. Accessed 16 June 2017
  3. 3.
    Tostain JL and Blanc F (2008) Testosterone deficiency: a common, unrecognized syndrome. Nat Clin Pract Urol 5:388–396. Accessed 16 June 2017
  4. 4.
    Traish AM, Miner MM, Morgentaler A, et al (2011) Testosterone deficiency. Am J Med 124:578–587. Accessed 16 June 2017
  5. 5.
    Wang C, Cunningham G, Dobs A, et al (2004) Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab 89:2085–2098. Accessed 16 June 2017
  6. 6.
    Aus G, Abbou CC, Bolla M, et al (2005) EAU Guidelines on prostate cancer. Eur Urol 48:546–551. Accessed 16 June 2017
  7. 7.
    Morgentaler A and Rhoden EL (2006) Prevalence of prostate cancer among hypogonadal men with prostate-specific antigen levels of 4.0 ng/mL or less. Urology 68:1263–1267. Accessed 9 Oct 2017
  8. 8.
    Morgentaler A, Bruning CO and DeWolf WC (1996) Occult prostate cancer in men with low serum testosterone levels. JAMA 276:1904–1906. Accessed 1 Dec 2017
  9. 9.
  10. 10.
    Traish AM, Haider A, Haider KS et al (2017) Long-term testosterone therapy improves cardiometabolic function and reduces risk of cardiovascular disease in men with hypogonadism. J Cardiovasc Pharmacol Ther 22:414–433.\ Accessed 30 Aug 2018
  11. 11.
    Haider KS, Haider A, Doros G, et al (2018) Long-term testosterone therapy improves urinary and sexual function, and quality of life in men with hypogonadism: results from a propensity matched subgroup of a controlled registry study. J Urol 199:257–265. Accessed 27 Aug 2018
  12. 12.
    Edwards BK, Noone A-M, Mariotto AB, et al (2014) Annual report to the nation on the status of cancer, 1975–2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer. Cancer 120:1290–1314. Accessed 16 June 2017
  13. 13.
    Discacciati A and Wolk A (2014) Lifestyle and dietary factors in prostate cancer prevention. In: Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer, Vol 202. pp 27–37. Accessed 16 June 2017
  14. 14.
    Rohrmann S, Linseisen J, Allen N et al (2013) Smoking and the risk of prostate cancer in the European Prospective Investigation into cancer and nutrition. Br J Cancer 108:708–714. Accessed 16 June 2017
  15. 15.
    Ramasamy R, Schlegel P, Fisher E (2012) Testosterone replacement and prostate cancer. Indian J Urol 28:123CrossRefGoogle Scholar
  16. 16.
    Eisenberg ML, Li S, Betts P et al (2015) Testosterone therapy and cancer risk. BJU Int 115:317–321CrossRefGoogle Scholar
  17. 17.
    Amory JK, Watts NB, Easley KA, et al (2004) Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab 89:503–510. Accessed 16 June 2017
  18. 18.
    Seidman SN and Klein DF (2004) AA2500 Testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J Clin Endocrinol Metab 89:6358–6359. Accessed 16 June 2017
  19. 19.
    Shabsigh R, Crawford ED, Nehra A, et al (2009) Testosterone therapy in hypogonadal men and potential prostate cancer risk: a systematic review. Int J Impot Res 21:9–23. Accessed 18 May 2017
  20. 20.
    Marks LS, Mazer NA, Mostaghel E, et al (2006) Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism. JAMA 296:2351. Accessed 16 June 2017
  21. 21.
    National Cancer Institute (2012) Prostate-specific antigen (PSA) test. Accessed 16 June 2017
  22. 22.
    Wolf AMD, Wender RC, Etzioni RB, et al (2010) American cancer society guideline for the early detection of prostate cancer: update 2010. CA Cancer J Clin 60:70–98. Accessed 16 June 2017
  23. 23.
    Morgentaler A (2006) Testosterone therapy for men at risk for or with history of prostate cancer. Curr Treat Options Oncol 7:363–369CrossRefGoogle Scholar
  24. 24.
    Traish AM, Haider A, Haider KS, et al (2017) Long-term testosterone therapy improves cardiometabolic function and reduces risk of cardiovascular disease in men with hypogonadism. J Cardiovasc Pharmacol Ther 22:414–433. Accessed 27 Aug 2018
  25. 25.
    Austin PC (2011) An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res 46:399–424. Accessed 27 Aug 2018

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Xiao Zhang
    • 1
  • Yan Zhong
    • 2
  • Farid Saad
    • 3
    • 4
  • Karim Haider
    • 5
  • Ahmad Haider
    • 5
  • Xiaohui Xu
    • 1
    Email author
  1. 1.Department of Epidemiology and Biostatistics, School of Public HealthTexas A&M UniversityCollege StationUSA
  2. 2.Department of StatisticsTexas A&M UniversityCollege StationUSA
  3. 3.Global Medical Affairs Andrology, Bayer AGBerlinGermany
  4. 4.Research DepartmentGulf Medical UniversityAjmanUAE
  5. 5.Private Urology PracticeBremerhavenGermany

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