Ashraful Hoque1, Song Yao2, Cathee Till3, Alan R Kristal3, Phyllis J Goodman3, Ann W Hsing4, Catherine M Tangen3, Elizabeth A Platz5, Frank Z Stanczyk6, Juergen K V Reichardt7, Adrie vanBokhoven8, Marian L Neuhouser3, Regina M Santella9, William D Figg10, Douglas K Price10, Howard L Parnes11, Scott M Lippman12, Christine B Ambrosone2, Ian M Thompson13. 1. Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: ahoque@mdanderson.org. 2. Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY. 3. Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA. 4. Cancer Prevention Institute of California, Fremont, CA. 5. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. 6. Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA; Department of Preventive Medicine, University of Southern California, Los Angeles, CA. 7. School of Pharmacy and Molecular Sciences, James Cook University, Townsville, Queensland, Australia. 8. Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO. 9. Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY. 10. Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD. 11. Prostate and Urologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD. 12. Moores Cancer Center, University of California San Diego, San Diego, CA. 13. Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX.
Abstract
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.
RCT Entities:
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 finasteridedecreased 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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