Effect of finasteride on serum androstenedione and risk of prostate cancer within the prostate cancer prevention trial: differential effect on high- and low-grade disease.
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.


CONCLUSIONS
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.
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: ahoque@mdanderson.org.
Ashraful
A
Hoque
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY.
Song
S
Yao
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA.
Cathee
C
Till
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA.
Alan R
AR
Kristal
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA.
Phyllis J
PJ
Goodman
Cancer Prevention Institute of California, Fremont, CA.
Ann W
AW
Hsing
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA.
Catherine M
CM
Tangen
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Elizabeth A
EA
Platz
Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA; Department of Preventive Medicine, University of Southern California, Los Angeles, CA.
Frank Z
FZ
Stanczyk
School of Pharmacy and Molecular Sciences, James Cook University, Townsville, Queensland, Australia.
Juergen K V
JK
Reichardt
Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO.
Adrie
A
vanBokhoven
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA.
Marian L
ML
Neuhouser
Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY.
Regina M
RM
Santella
Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
William D
WD
Figg
Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
Douglas K
DK
Price
Prostate and Urologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD.
Howard L
HL
Parnes
Moores Cancer Center, University of California San Diego, San Diego, CA.
Scott M
SM
Lippman
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY.
Christine B
CB
Ambrosone
Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX.
Ian M
IM
Thompson
D000735:Androstenedione / Q000097:blood*; D016022:Case-Control Studies; D004311:Double-Blind Method; D018120:Finasteride / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control*; D018570:Risk Assessment
D000735:Androstenedione; D018120:Finasteride