Ageless Forever Anti-Aging News Blog

Incidence of Prostate Cancer after Testosterone Therapy for up to 17 years

One of the major concerns among doctors and patients with testosterone therapy is its allegedly negative effect on the prostate.[1] However, according to the current ISA, ISSAM, EAU, EAA, ASA clinical guidelines, there is no conclusive evidence that testosterone therapy increases the risk of prostate cancer or benign prostatic hyperplasia.[2]
 
The guidelines also state that there is also no evidence that testosterone treatment will convert subclinical prostate cancer to clinically detectable prostate cancer.[2]
 
Despite this, many men are being denied testosterone therapy because of undue fears that it would cause harm to the prostate. Here I summarize the results from a study that investigated incidence of prostate cancer with testosterone therapy for up to 17 years.[3]
 

KEY POINTS 

 
* In the study population who had been treated with testosterone therapy fro up to 17 years, there were 11 cases of prostate cancer, translating into a proportion of 1.08%.[3]
 
* This prostate cancer incidence (1.08%) is much lower than that reported in the general population of men who are not on testosterone therapy:
 
- The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial on prostate-cancer mortality reported a prostate cancer incidence of 7.35% among 38,345 US men aged 55-74 years who were followed for 7 years.[4]
 
-  The European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a prostate cancer incidence of 9.6% among 72,891 men aged 50-74 years who were followed for 11 years.[5]
 
* This study shows that testosterone treatment with Nebido® for up to 17 years does not increase the risk of prostate cancer [3], which supports previously presented new insights on the testosterone - prostate relationship, and the saturation limit of androgen-dependent prostate growth.[6, 7]
 
* Testosterone therapy has no clinically significant adverse impact on prostate cancer incidence among men regardless of administration method.[8]
 

What is known

 
Medical students and doctors have been indoctrinated since the 1940s that high testosterone levels supposedly promote the development of prostate cancer, that low testosterone is protective, and that the administration of testosterone to a man with subclinical or existing prostate cancer would speed up its progression.[9] This fear is also the most common reason for doctors' reluctance to prescribe testosterone replacement therapy, even in hypogonadal men [1, 10]. This belief deprives many hypogonadal men of important health benefits, which unnecessarily causes severe harm due to the well documented detrimental health consequences of testosterone deficiency, which I covered in a previous article "Adverse health effects of testosterone deficiency in men".
However, a growing number of studies refute this old testosterone-prostate belief.
 

What this study adds

 
In the study by Haider et al, 1,023 hypogonadal men with total testosterone was ≤12.1 nmol/L (350 ng/dL) and symptoms of hypogonadism received testosterone therapy with testosterone undecanoate (1000 mg) (Nebido®) in intervals of 12 weeks following an initial interval of 6 weeks, for up to 17 years. Age at baseline was 41-58 years.
 
The notable result in this study is that the incidence of prostate cancer among men who had been treated with testosterone therapy using Nebido® for 17 years was lower than the incidence of prostate cancer that is seen in the general population of men who are not treated with testosterone therapy; only 1.08% [3] compared to 7.35 to 9.6%.[4, 5] The results from this study are consistent with findings from another study that investigated prostate outcomes after treatment with testosterone patches for 6 years, which also documented the prostate safety of testosterone therapy.[11]
 
This 17-year long study with Nebido® clearly demonstrates that testosterone therapy does not increase risk for development of prostate cancer. It also supports previous observations showing no association between endogenous testosterone levels and prostate cancer [12, 13], and meta-analyses which conclude that there is no clinically significant adverse impact on prostate cancer incidence among men on testosterone therapy, regardless of the administration method.[8, 14]
 
There is also no correlation between testosterone therapy and increased aggressiveness of prostate cancer at diagnosis.[15] A systematic review of testosterone therapy and potential prostate cancer risk among men with and without a history of prostate cancer found that no study demonstrated that testosterone therapy for hypogonadism increased prostate cancer risk or worsened Gleason grade of detected cancer in treated vs. untreated men.[16] Withholding testosterone therapy in hypogonadal men, also in men who have been successfully treated for prostate cancer, is not justified.[17]
 
Despite the widespread belief that testosterone therapy is contraindicated in hypogonadal men with known or suspected prostate cancer [18], there is no convincing evidence that the normalization of testosterone levels would increase risk for progression of prostate cancer.[6, 7] In view of the current available evidence, clinicians are compelled to consider these new data and abandon the old-school indoctrinated line of thought. [7]
 
According to Dr. Morgentaler, a leading clinician and researcher specializing in testosterone therapy and prostate safety, the negative view of testosterone with regard to prostate cancer should be recognized for what it is - guilt by association.[19] Dr. Morgentaler also urges clinicians to turn conventional wisdom upside-down by correctly stating: "Finally, after 7 decades of circumstantial evidence pointing us in the wrong direction, perhaps it is time to consider the once unthinkable: a testosterone therapy trial of sufficient size and duration to determine whether normalization of serum testosterone in older men may reduce the risk of prostate cancer, particularly high-risk prostate cancer."[20]
 

References:

1.            Gooren, L.J. and H.M. Behre, Diagnosing and treating testosterone deficiency in different parts of the world: changes between 2006 and 2010. Aging Male, 2012. 15(1): p. 22-7.

2.            Wang, C., et al., Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. Eur Urol, 2009. 55(1): p. 121-30.

3.            Haider, A., et al., Incidence of Prostate Cancer in Hypogonadal Men Receiving Testosterone Therapy: Observations from Five Year-median Follow-up of Three Registries. J Urol, 2014.

4.            Andriole, G.L., et al., Mortality results from a randomized prostate-cancer screening trial. N Engl J Med, 2009. 360(13): p. 1310-9.

5.            Schroder, F.H., et al., Prostate-cancer mortality at 11 years of follow-up. N Engl J Med, 2012. 366(11): p. 981-90.

6.            Morgentaler, A. and A.M. Traish, Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. European Urology, 2009. 55(2): p. 310-20.

7.            Khera, M., et al., A new era of testosterone and prostate cancer: from physiology to clinical implications. European Urology, 2014. 65(1): p. 115-23.

8.            Cui, Y. and Y. Zhang, The effect of androgen-replacement therapy on prostate growth: a systematic review and meta-analysis. European Urology, 2013. 64(5): p. 811-22.

9.            Khera, M., et al., A new era of testosterone and prostate cancer: from physiology to clinical implications. Eur Urol, 2014. 65(1): p. 115-23.

10.          Atan, A., et al., Serum testosterone level, testosterone replacement treatment, and prostate cancer. Adv Urol, 2013. 2013: p. 275945.

11.          Raynaud, J.P., et al., Prostate-specific antigen (PSA) concentrations in hypogonadal men during 6 years of transdermal testosterone treatment. BJU International, 2013. 111(6): p. 880-90.

12.          Muller, R.L., et al., Serum testosterone and dihydrotestosterone and prostate cancer risk in the placebo arm of the Reduction by Dutasteride of Prostate Cancer Events trial. European Urology, 2012. 62(5): p. 757-64.

13.          Roddam, A.W., et al., Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. Journal of the National Cancer Institute, 2008. 100(3): p. 170-83.

14.          Fernandez-Balsells, M.M., et al., Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab, 2010. 95(6): p. 2560-75.

15.          Kaplan, A.L. and J.C. Hu, Use of testosterone replacement therapy in the United States and its effect on subsequent prostate cancer outcomes. Urology, 2013. 82(2): p. 321-6.

16.          Shabsigh, R., et al., Testosterone therapy in hypogonadal men and potential prostate cancer risk: a systematic review. International Journal of Impotence Research, 2009. 21(1): p. 9-23.

17.          Rinnab, L., et al., [Testosterone replacement therapy and prostate cancer. The current position 67 years after the Huggins myth]. Urologe. Ausgabe A, 2009. 48(5): p. 516-22.

18.          Bhasin, S., et al., Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism, 2010. 95(6): p. 2536-59.

19.          Morgentaler, A., Guilt by association: a historical perspective on Huggins, testosterone therapy, and prostate cancer. J Sex Med, 2008. 5(8): p. 1834-40.

20.          Morgentaler, A., Turning conventional wisdom upside-down: low serum testosterone and high-risk prostate cancer. Cancer, 2011. 117(17): p. 3885-8.

 
Last modified on Monday, 15 September 2014 23:51
Monica Mollica

Medical Writer & Nutritionist

MSc in Nutrition

University of Stockholm & Karolinska Institute, Sweden 

   Baylor University, TX, USA

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