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

Ashraful Hoque; Song Yao; Cathee Till; Alan R. Kristal; Phyllis J. Goodman; Ann W. Hsing; Catherine M. Tangen; Elizabeth A. Platz; Frank Z. Stanczyk; Juergen K.V. Reichardt; Adrie Vanbokhoven; Marian L. Neuhouser; Regina M. Santella; William D. Figg; Douglas K. Price; Howard L. Parnes; Scott M. Lippman; Christine B. Ambrosone; Ian M. Thompson

doi:10.1016/j.urology.2014.11.024

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

Ashraful Hoque, Song Yao, Cathee Till, Alan R. Kristal, Phyllis J. Goodman, Ann W. Hsing, Catherine M. Tangen, Elizabeth A. Platz, Frank Z. Stanczyk, Juergen K.V. Reichardt, Adrie Vanbokhoven, Marian L. Neuhouser, Regina M. Santella, William D. Figg, Douglas K. Price, Howard L. Parnes, Scott M. Lippman, Christine B. Ambrosone, Ian M. Thompson

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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.

Original language	English (US)
Pages (from-to)	616-620
Number of pages	5
Journal	Urology
Volume	85
Issue number	3
DOIs	https://doi.org/10.1016/j.urology.2014.11.024
State	Published - Mar 1 2015

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Urology

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10.1016/j.urology.2014.11.024

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Hoque, A., Yao, S., Till, C., Kristal, A. R., Goodman, P. J., Hsing, A. W., Tangen, C. M., Platz, E. A., Stanczyk, F. Z., Reichardt, J. K. V., Vanbokhoven, A., Neuhouser, M. L., Santella, R. M., Figg, W. D., Price, D. K., Parnes, H. L., Lippman, S. M., Ambrosone, C. B., & Thompson, I. M. (2015). 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. Urology, 85(3), 616-620. https://doi.org/10.1016/j.urology.2014.11.024

Hoque, A, Yao, S, Till, C, Kristal, AR, Goodman, PJ, Hsing, AW, Tangen, CM, Platz, EA, Stanczyk, FZ, Reichardt, JKV, Vanbokhoven, A, Neuhouser, ML, Santella, RM, Figg, WD, Price, DK, Parnes, HL, Lippman, SM, Ambrosone, CB & Thompson, IM 2015, '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', Urology, vol. 85, no. 3, pp. 616-620. https://doi.org/10.1016/j.urology.2014.11.024

@article{2a5b09ab04e04a2eb8777a68397338cd,

title = "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",

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.",

author = "Ashraful Hoque and Song Yao and Cathee Till and Kristal, {Alan R.} and Goodman, {Phyllis J.} and Hsing, {Ann W.} and Tangen, {Catherine M.} and Platz, {Elizabeth A.} and Stanczyk, {Frank Z.} and Reichardt, {Juergen K.V.} and Adrie Vanbokhoven and Neuhouser, {Marian L.} and Santella, {Regina M.} and Figg, {William D.} and Price, {Douglas K.} and Parnes, {Howard L.} and Lippman, {Scott M.} and Ambrosone, {Christine B.} and Thompson, {Ian M.}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = mar,

day = "1",

doi = "10.1016/j.urology.2014.11.024",

language = "English (US)",

volume = "85",

pages = "616--620",

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TY - JOUR

T1 - Effect of finasteride on serum androstenedione and risk of prostate cancer within the prostate cancer prevention trial

T2 - Differential effect on high- and low-grade disease

AU - Hoque, Ashraful

AU - Yao, Song

AU - Till, Cathee

AU - Kristal, Alan R.

AU - Goodman, Phyllis J.

AU - Hsing, Ann W.

AU - Tangen, Catherine M.

AU - Platz, Elizabeth A.

AU - Stanczyk, Frank Z.

AU - Reichardt, Juergen K.V.

AU - Vanbokhoven, Adrie

AU - Neuhouser, Marian L.

AU - Santella, Regina M.

AU - Figg, William D.

AU - Price, Douglas K.

AU - Parnes, Howard L.

AU - Lippman, Scott M.

AU - Ambrosone, Christine B.

AU - Thompson, Ian M.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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.

AB - 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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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

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