Objective: To evaluate the effect of finasteride on serum androst-4-ene-3,17-dione (androstenedione) and its association with prostate cancer risk among subjects who participated in the Prostate Cancer Prevention Trial.
Methods: We analyzed serum androstenedione levels in 317 prostate cancer cases and 353 controls, nested in the Prostate Cancer Prevention Trial, a randomized placebo-controlled trial that found finasteride decreased prostate cancer risk. Androstenedione is the second most important circulating androgen in men besides testosterone and also a substrate for 5α-reductase enzyme.
Results: We observed a 22% increase in androstenedione levels compared with the baseline values in subjects who were treated with finasteride for 3 years. This significant increase did not vary by case-control status. Adjusted odds ratio and 95% confidence interval for the third tertile of absolute change in androstenedione levels compared with the first tertile were 0.42 (95% confidence interval, 0.19-0.94) for low-grade (Gleason score <7) cases. Similar results were observed when analyzed using percent change. There were no significant associations between serum androstenedione levels and the risk of high-grade disease.
Conclusion: The results of this nested case-control study confirm that finasteride blocks the conversion of testosterone to dihydrotestosterone (DHT) and of androstenedione to 5α-androstanedione-3,17-dione, which also leads to the reduction of DHT formation. This decrease in DHT may help reduce the risk of low-grade prostate cancer in men. Our data on a differential effect of androstenedione also suggest that some high-grade prostate cancers may not require androgen for progression.
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| http://dx.doi.org/10.1016/j.urology.2014.11.024 | DOI Listing |
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