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New Insight into the Relation Between Sex Hormones and Prostate Cancer

February 20th, 2008

Serum levels of androgens and oestrogens were not related to risk for developing prostate cancer in initially healthy men.

During the past several decades, many hypotheses about prostate cancer etiology have gained wide support, including family history, genetics, and consuming a Western diet. Elevated androgen levels have long been considered a likely risk factor, and many studies have been conducted in an attempt to characterize this attribute. For example, the Prostate Cancer Prevention Trial (PCPT) — the results of which demonstrated a 25% lower rate of prostate cancer in men who were randomized to receive the 5-reductase inhibitor finasteride — was designed, in part, to determine whether elevated androgen levels were associated with higher risk for developing disease (N Engl J Med 2003; 349:215).
In an unusual research effort, investigators who had published prospective studies on prostate cancer risk and endogenous sex hormone concentrations were invited to join a collaborative group. Most investigators who were contacted agreed to participate; data were contributed from 18 prospective studies (3886 men with prostate cancer and 6438 controls), which represented 95% of data available worldwide. In these studies, blood samples were collected from healthy men who were then followed to identify those who developed prostate cancer. Laboratory analyses were performed on blood samples from patients with incident prostate cancer and from matched control subjects. Data, including patient characteristics and all lab variables, were analyzed in a conditional logistic regression that was stratified by study, age at recruitment (2-year age bands), and date of recruitment (single year).
No significant associations were found between serum concentrations of any androgen or estrogen and risk for prostate cancer. Additionally, no association was noted between risk for prostate cancer and concentrations of androstanediol glucuronide, androstenedione, dehydroepiandrosterone sulfate, estradiol, or free estradiol. Levels of sex-hormone binding globulin were significantly and inversely related to prostate cancer risk. No interstudy heterogeneity was found in the estimated trends for any hormone, and adjustment for potential confounders did not affect risk estimates.
Comment: The findings from this impressive collaborative effort provide an important addition to our understanding of prostate cancer aetiology. As editorialists note, “By confirming the lack of evidence to support an androgen–prostate cancer hypothesis, the study obliges the scientific community to move past a seductive, clinically relevant, and biologically plausible hypothesis and get on with the difficult task of exploring, analyzing, and characterizing modifiable risk factors for prostate cancer.”
Published in Journal Watch Oncology and Haematology February 19, 2008

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