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Pre-diagnostic Circulating Sex Hormones Are Not Associated with Mortality for Patients with Prostate Cancer
Boris Gershman, MD1, Irene M. Shui, ScD2, Meir Stampfer, MD, DrPH2, Elizabeth A. Platz, ScD3, Peter H. Gann, MD, ScD4, Howard L. Sesso, ScD2, Edward Giovannucci, MD, ScD2, Lorelei A. Mucci, ScD2.
1Massachusetts General Hospital, Boston, MA, USA, 2Harvard School of Public Health, Boston, MA, USA, 3Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 4University of Illinois at Chicago, Chicago, IL, USA.

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 patients with prostate cancer. We examined the association between pre-diagnostic circulating sex hormones and lethal prostate cancer in men diagnosed with prostate cancer in two prospective cohort studies, the Physicians' Health Study (PHS) and the Health Professionals Follow-up Study (HPFS).
METHODS: We included 918 prostate cancer cases (700 HPFS; 218 PHS) who provided pre-diagnostic blood samples in which circulating sex hormone levels were assayed. The primary endpoint was lethal prostate cancer (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 pre-diagnostic sex hormone levels with time from diagnosis to development of lethal prostate cancer or total mortality.
RESULTS: Prostate cancer cases were followed for a mean of 12.1 ± 4.8 years after diagnosis. Mean age at blood draw and diagnosis were 65.0 ± 7.6 years and 68.8 ± 7.2 years, respectively. We confirmed 146 cases of lethal prostate cancer and 404 deaths overall. Using Cox proportional hazard models adjusted for age at diagnosis, body mass index (BMI), physical activity, and smoking status, we found no significant association between quartile of total testosterone, SHBG, SHBG-adjusted testosterone, free testosterone, dihydrotestosterone, androstanediol glucuronide, or estradiol and lethal prostate cancer or total mortality. Similarly, we found no association in models further adjusted for Gleason score and TNM stage.
CONCLUSIONS: We found no association between pre-diagnostic circulating sex hormones and lethal prostate cancer or overall mortality. Our results suggest that reverse causation may be responsible in prior studies that noted adverse outcomes for patients with low circulating androgens.


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