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Low testosterone levels predict prostate cancer: Hormonal pattern as a useful tool for prostate cancer screening, "Beyond the Abstract," by Eduard García-Cruz, MD, et al.

BERKELEY, CA (UroToday.com) - The relationship between testosterone and prostate cancer (PCa) is a known and well-established association since the finding of Huggins and Hodges that a chemical or surgical castration entailed a regression of the PCa, whereas the administration of T would accelerate the development of PCa.[1, 2]

However, recent studies have questioned the above association, bringing into account that although testosterone levels decrease within the elderly, the prevalence of prostate cancer is inversely rising.[3, 4] In the same line, other study groups have evaluated the possible association between sex hormones and the subsequent development of PCa, finding no relationship.[5, 6, 7] In their study, Severi et al. concluded that higher levels of testosterone and adrenal androgens were associated with reduced risk of aggressive prostate cancer.[5] In order to shed light on these recent findings, our study group aimed to assess the hormonal patterns, exhibited by men, referred to our center for prostate biopsy.

Morgentaler et al. conducted a study to determine the prevalence of occult prostate cancer in men with low serum testosterone or free testosterone levels, observing a higher prevalence of prostate cancer detected, by biopsy, in this cohort of patients, despite having normal PSA levels as well as digital rectal examination.[8] Previous analyses have showed that high T levels are not related to greater PCa detection.[9] On the other hand, some manuscripts have shown a negative relationship between PCa and T levels.[10, 11] In men with PCa, it has been shown that low T levels might be related to higher staging and higher Gleason scores.[12, 13] Discrepant results have been shown after prostate cancer treatment and T levels, with a variety of papers supporting the notion that lower T levels might be associated to higher stage, higher grade and higher risk of progression.

In line with the abovementioned studies, our results showed that low levels of testosterone are predictive of PCa detection, specifically low bioavailable testosterone. Furthermore, higher levels of sex hormone-binding globulin (SHBG) were also related to PCa. Our previous insights into this topic showed that men with PCa are more likely to have higher SHBG than those without PCa; those men with low T levels were more likely to have PCa with a higher risk of progression and HG-PIN men presented more positive re-biopsy if they had low T levels.

Regarding the hormonal preoperative levels and PCa prognosis, we observed no relationship between hormonal pattern and worse cancer prognosis or higher biochemical recurrence, although a certain trend (non-statistically significant) towards biochemical recurrence in men with low T men was observed. In any case, no relationship was found between high T and worse PCa features or evolution.

In conclusion, not only are high levels of testosterone not related to a greater risk of developing prostate cancer, but on the contrary, we observed lower levels of free testosterone and higher levels of SHBG in men with prostate cancer. From our point of view, hormonal pattern, including free and bioavailable testosterone and SHBG, could be a useful tool within screening for prostate cancer, together with PSA and digital rectal examination and the upcoming advances in imaging.

References:

  1. Huggins C, Hodges CV (1941) "The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate". Cancer Res 1:293-297.
  2. Huggins C, Stevens R et al. (1941) "Studies on prostatic cancer: II. The effects of castration on advanced carcinoma of the prostate gland". Arch Surg 43(2):209–223.
  3. Gray A, Feldman HA et al. (1991) "Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study". J Clin Endocrinol Metab. 73(5):1016–1025.
  4. Morgentaler A. (2008) "Guilt by association: a historical perspective on Huggins, testosterone therapy, and prostate cancer". J Sex Med. 5(8):1834–1840.
  5. Severi G, Morris HA et al. (2006) "Circulating steroid hormones and the risk of prostate cancer." Cancer Epidemiol Biomarkers Prev. 15(1):86–91.
  6. Daniels NA, Nielson CM et al. (2010) "Sex hormones and the risk of incident prostate cancer." Urology. 76(5):1034–1040.
  7. Mohr BA, Feldman HA et al. (2001) "Are serum hormones associated with the risk of prostate cancer? Prospective results from the Massachusetts Male Aging Study." Urology. 57(5):930–935.
  8. Morgentaler A, Bruning CO et al. (1996) "Occult prostate cancer in men with low serum testosterone levels." JAMA. 18;276(23):1904–1906.
  9. Stattin P, Lumme S et al. (2004) "High levels of circulating testosterone are not associated with increased prostate cancer risk: a pooled prospective study." Int J Cancer. 108(3):418–424.
  10. Sofikerim M, Eskicorapci S et al. (2007) "Hormonal predictors of prostate cancer". Urol Int. 2007;79(1):13–18.
  11. Yano M, Imamoto T et al. (2007) "The clinical potential of pretreatment serum testosterone level to improve the efficiency of prostate cancer screening." Eur Urol. 51(2):375–380.
  12. Isom-Batz G, Bianco FJ et al. (2005) "Testosterone as a predictor of pathological stage in clinically localized prostate cancer." J Urol. 173(6):1935–1937.
  13. Schatzl G, Madersbacher S et al. (2001) "High-grade prostate cancer is associated with low serum testosterone levels". Prostate. 47(1):52–58.

Written by:
Andrea Sallent,a Eduard García-Cruz, MD,b Roberto Castañeda-Argaiz, MD,b Albert Carrión, MD,b Joan Alcover, MD,b Asier Leibar-Tamayo, MD,c Javier Romero-Otero, MD,d and Antonio Alcarazb as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

a School of Medicine, Hospital Clínic Barcelona
University of Barcelona (Spain)
b Urology Department
Hospital Clinic de Barcelona, Spain
c Urology Department
Hospital de Galdakao Usansolo, Vizcaya (Spain)
d Urology Department
Hospital 12 de Octubre, Madrid (Spain)

Author for Correspondence:
Eduard García-Cruz, MD
Urology Department
Hospital Clinic de Barcelona
Villarroel, 170
08036 Barcelona (Spain)
Email:

 

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