70426
document
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 . 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 .
70427
Intervention_Pharmacological
finasteride
70428
Intervention_Pharmacological
finasteride
70429
Intervention_Control
placebo-controlled
70430
Intervention_Pharmacological
finasteride
70431
Participant_Condition
Prostate Cancer
70432
Participant_Sample-size
317
70433
Participant_Sample-size
353