BERKELEY, CA (UroToday.com) -
Researchers found that higher concentrations of percent-free testosterone (%FT) are associated with an increased risk of high-grade prostate cancer.
| "...these results are intriguing and open new insights on the hormonal interactions between androgens and prostate cancer." |
Simone Albisinni, MD, of the Department of Urology of Sant’ Andrea Hospital, Rome, and colleagues recently reported in Urology (2012;80:162-168) their research examining over 800 Caucasian men undergoing 12-core prostate biopsy due to an elevation of PSA or an abnormal digital rectal examination. Serum total testosterone and free testosterone were measured prior to biopsy, and their association with low- (Gleason ≤6) and high-grade (Gleason ≥7) prostate cancer was explored. A new variable called percent free testosterone (%FT) was calculated by the investigators as free/total testosterone; total and free testosterone had ever been examined as a single variable before. On multivariate analysis, %FT was a significant predictor of high-grade disease. Men were also divided in tertiles, and those in the highest (%FT>0.23%) had a significant two-fold risk of being diagnosed with high-grade prostate cancer. Testosterone and free testosterone levels were not significantly associated with low- or high-grade PCa. As such, it is possible that while absolute androgen levels are not predictive of high-grade prostate cancer, their relative concentrations might (a concurrent elevated free testosterone and low total testosterone).
Given that obese men have lower total testosterone levels compared to their slimmer counterparts (and thus a higher %FT), researchers also explored whether the association between %FT and cancer outcomes varied by obesity state (considering obese men with a BMI of 30 kg/m2) including an interaction term in the multivariate model and evaluating the p-value using the Wald test. However, as the interaction between %FT and obesity was not significant (p=0.39), it appears that obesity does not modify the association between %FT and cancer outcomes.
The biological rationale for the observed findings has not yet been elucidated. Dr. Albisinni and his team have proposed possible explanations that, although plausible, are speculative and need further research to be supported. It is possible that the altered hormonal microenvironment may determine an overexpression of the androgen receptor (as a consequence of low total testosterone) and its concurrent overactivation due to the elevated free testosterone penetrating in the prostatic cells. Moreover, investigators hypothesized that, as extracellular total testosterone appears to activate a proapoptotic receptor on the cell membrane, while free testosterone stimulates the cell through the intracellular androgen receptor, the low total testosterone concentrations may be responsible for a simultaneous reduction of this extracellular receptor-mediated apoptotic pathway. This could lead to an increased proliferation.
Indeed these results are intriguing and open new insights on the hormonal interactions between androgens and prostate cancer. However, given some limitations of the study, such as the pathological evaluation through biopsy specimens and the mono-ethnicity of the population studied, further studies are needed to confirm these findings and fully elucidate the complex mechanisms that underlie the observed results.
Written by:
Simone Albisinni, MD 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.
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