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

doi:10.1016/j.eururo.2013.01.003

. 2014 Apr;65(4):683-9.

doi: 10.1016/j.eururo.2013.01.003. Epub 2013 Jan 11.

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

Boris Gershman¹, Irene M Shui², Meir Stampfer³, Elizabeth A Platz⁴, Peter H Gann⁵, Howard L Sesso⁶, Natalie DuPre², Edward Giovannucci³, Lorelei A Mucci⁷

Affiliations

¹ Department of Urology, Massachusetts General Hospital, Boston, MA, USA.
² Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
³ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁴ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁵ Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA.
⁶ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: lmucci@hsph.harvard.edu.

PMID: 23340241
PMCID: PMC3664134
DOI: 10.1016/j.eururo.2013.01.003

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

Boris Gershman et al. Eur Urol. 2014 Apr.

. 2014 Apr;65(4):683-9.

doi: 10.1016/j.eururo.2013.01.003. Epub 2013 Jan 11.

Authors

Boris Gershman¹, Irene M Shui², Meir Stampfer³, Elizabeth A Platz⁴, Peter H Gann⁵, Howard L Sesso⁶, Natalie DuPre², Edward Giovannucci³, Lorelei A Mucci⁷

Affiliations

¹ Department of Urology, Massachusetts General Hospital, Boston, MA, USA.
² Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
³ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁴ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁵ Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA.
⁶ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: lmucci@hsph.harvard.edu.

PMID: 23340241
PMCID: PMC3664134
DOI: 10.1016/j.eururo.2013.01.003

Abstract

Background: Sex hormones play an important role in the growth and development of the prostate, and low androgen levels have been suggested to carry an adverse prognosis for men with prostate cancer (PCa).

Objective: To examine the association between prediagnostic circulating sex hormones and lethal PCa in two prospective cohort studies, the Physicians' Health Study (PHS) and the Health Professionals Follow-up Study (HPFS).

Design, setting, and participants: We included 963 PCa cases (700 HPFS; 263 PHS) that provided prediagnostic blood samples, in 1982 for PHS and in 1993-1995 for HPFS, in which circulating sex hormone levels were assayed.

Outcome measures and statistical analysis: The primary end point was lethal PCa (defined as cancer-specific mortality or development of metastases), and we also assessed total mortality through March 2011. We used Cox proportional hazards models to evaluate the association of prediagnostic sex hormone levels with time from diagnosis to development of lethal PCa or total mortality.

Results and limitations: PCa cases were followed for a mean of 12.0±4.9 yr after diagnosis. We confirmed 148 cases of lethal PCa and 421 deaths overall. Using Cox proportional hazard models, we found no significant association between quartile of total testosterone, sex hormone binding globulin (SHBG), SHBG-adjusted testosterone, free testosterone, dihydrotestosterone, androstanediol glucuronide, or estradiol and lethal PCa or total mortality. In subset analyses stratified by Gleason score, TNM stage, age, and interval between blood draw and diagnosis, there was also no consistent association between lethal PCa and sex hormone quartile.

Conclusions: We found no overall association between prediagnostic circulating sex hormones and lethal PCa or total mortality. Our null results suggest that reverse causation may be responsible in prior studies that noted adverse outcomes for men with low circulating androgens.

Keywords: Androgens; Mortality; Prostate cancer; Sex hormones; Testosterone.

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Conflict of interest statement

Financial disclosures: Lorelei A. Mucci certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/ affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None.

Comment in

Androgens and prostate cancer: we are still (almost) completely ignorant.
Salonia A. Salonia A. Eur Urol. 2014 Apr;65(4):690-1; discussion 691-2. doi: 10.1016/j.eururo.2013.02.041. Epub 2013 Mar 13. Eur Urol. 2014. PMID: 23522909 No abstract available.

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References

1. Imamoto T, Suzuki H, Yano M, et al. The role of testosterone in the pathogenesis of prostate cancer. Int J Urol. 2008;15:472–80. - PubMed
1. 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. - PMC - PubMed
1. Platz EA, Leitzmann MF, Rifai N, et al. Sex steroid hormones and the androgen receptor gene CAG repeat and subsequent risk of prostate cancer in the prostate-specific antigen era. Cancer Epidemiol Biomarkers Prev. 2005;14:1262–9. - PubMed
1. 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
1. 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

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[1] Imamoto T, Suzuki H, Yano M, et al. The role of testosterone in the pathogenesis of prostate cancer. Int J Urol. 2008;15:472–80. - PubMed

[2] Imamoto T, Suzuki H, Yano M, et al. The role of testosterone in the pathogenesis of prostate cancer. Int J Urol. 2008;15:472–80. - PubMed

[3] 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. - PMC - PubMed

[4] 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. - PMC - PubMed

[5] Platz EA, Leitzmann MF, Rifai N, et al. Sex steroid hormones and the androgen receptor gene CAG repeat and subsequent risk of prostate cancer in the prostate-specific antigen era. Cancer Epidemiol Biomarkers Prev. 2005;14:1262–9. - PubMed

[6] Platz EA, Leitzmann MF, Rifai N, et al. Sex steroid hormones and the androgen receptor gene CAG repeat and subsequent risk of prostate cancer in the prostate-specific antigen era. Cancer Epidemiol Biomarkers Prev. 2005;14:1262–9. - PubMed

[7] 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

[8] 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

[9] 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

[10] 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

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

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

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Conflict of interest statement

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