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Prediagnostic circulating sex hormones are not associated with mortality for men with prostate cancer, "Beyond the Abstract," by Boris Gershman, Irene M. Shui, and Lorelei A. Mucci

BERKELEY, CA (UroToday.com) - Androgens have historically played an important role in prostate cancer biology and have been a therapeutic target since the early description of androgen deprivation, by Huggins, in 1941.[1] Studies in recent years, however, have suggested that the relationship between sex hormones and prostate cancer is complex. For instance, a number of prospective epidemiologic studies have not observed a consistent association between prostate cancer incidence and circulating sex hormone levels.[2] Nonetheless, low pre-treatment testosterone has been associated with several adverse prognostic indicators, including higher Gleason score and advanced pathologic stage.[3, 4] We conducted an analysis of two large, prospective cohort studies and observed no association between pre-diagnostic circulating sex hormones and lethal prostate cancer or overall survival.[5]

Although the results of such studies appear to conflict, it is possible to reconcile their observations when we consider the timing of sex hormone exposure as well as the potential role for reverse causation. The epidemiologic studies that evaluated incident prostate cancer in relation to sex hormone levels utilized pre-diagnostic measurements – that is, taken before cancer diagnosis. In contrast, those studies that did observe a relationship between low circulating androgen levels and adverse prognostic markers used pre-treatment measurements – obtained after diagnosis but before treatment. In the latter case, low androgen levels may result from suppression by the cancer itself. Indeed, there is evidence for cancer-related gonadotropin suppression in several studies that noted an increase in the levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) following radical prostatectomy but not following TURP.[6, 7] It is also possible that the relationship between circulating sex hormones and prostate cancer biology is non-linear.[8]

Despite the null results of our study, there is still potential clinical utility in circulating sex hormone levels. For example, circulating testosterone levels may have value in cancer diagnosis and risk stratification. In addition, androgen deprivation remains a mainstay of the management of advanced prostate cancer, and pre-treatment testosterone levels have been shown to predict response to therapy.[9] Ultimately, additional studies are needed to characterize the role of sex hormones in the endocrine biology of prostate cancer, and this enhanced understanding should lead to improved clinical management.

References:

  1. Imamoto T, Suzuki H, Yano M, Kawamura K, Kamiya N, Araki K, et al. The role of testosterone in the pathogenesis of prostate cancer. Int.J.Urol. 2008;15 472-80.
  2. Endogenous Hormones and Prostate Cancer Collaborative Group, Roddam AW, Allen NE, Appleby P, Key TJ. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J.Natl.Cancer Inst. 2008;100 170-83.
  3. Hoffman MA, DeWolf WC, Morgentaler A. Is low serum free testosterone a marker for high grade prostate cancer?. J.Urol. 2000;163 824-7.
  4. Isom-Batz G, Bianco FJ,Jr, Kattan MW, Mulhall JP, Lilja H, Eastham JA. Testosterone as a predictor of pathological stage in clinically localized prostate cancer. J.Urol. 2005;173 1935-7.
  5. Gershman B, Shui IM, Stampfer M, et al. “Prediagnostic circulating sex hormones are not associated with mortality for men with prostate cancer.” European Urology. Epub Jan 2013.
  6. Madersbacher S, Schatzl G, Bieglmayer C, Reiter WJ, Gassner C, Berger P, et al. Impact of radical prostatectomy and TURP on the hypothalamic-pituitary-gonadal hormone axis. Urology 2002;60 869-74.
  7. Miller LR, Partin AW, Chan DW, Bruzek DJ, Dobs AS, Epstein JI, et al. Influence of radical prostatectomy on serum hormone levels. J.Urol. 1998;160 449-53.
  8. Salonia A, Abdollah F, Capitanio U, Suardi N, Briganti A, Gallina A, et al. Serum sex steroids depict a nonlinear u-shaped association with high-risk prostate cancer at radical prostatectomy. Clin.Cancer Res. 2012;18 3648-57.
  9. Chodak GW, Vogelzang NJ, Caplan RJ, Soloway M, Smith JA. Independent Prognostic Factors in Patients With Metastatic (Stage D2) Prostate Cancer. JAMA 1991;265 618-21.

 

Written by:
Boris Gershman,a Irene M. Shui,b Lorelei A. Mucci,b, c 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.

aDepartment of Urology, Massachusetts General Hospital, Boston, MA
bDepartment of Epidemiology, Harvard School of Public Health, Boston, MA
cChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA

Prediagnostic circulating sex hormones are not associated with mortality for men with prostate cancer - Abstract

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