Associations of serum sex steroid hormone and 5α-androstane-3α, 17β-diol glucuronide concentrations with prostate cancer risk among men treated with finasteride

Alan R. Kristal, Cathee Till, Catherine M. Tangen, Phyllis J. Goodman, Marian L. Neuhouser, Frank Z. Stanczyk, Lisa W. Chu, Sherfaraz K. Patel, Ian M. Thompson, Juergen K. Reichardt, Ashraful Hoque, Elizabeth A Platz, William D. Figg, Adrie Van Bokhoven, Scott M. Lippman, Ann W. Hsing

Research output: Contribution to journalArticle

Abstract

Background: Finasteride, an inhibitor of 5α-reductase (type II), lowers intraprostatic dihydrotestosterone (DHT), which is reflected in serum as reduced 5α-androstane-3α,17β-diol glucuronide (3α-dG). It also modestly increases serum testosterone (T), estrone (E1), and estradiol (E2). In this altered hormonal milieu, it is unknown whether serum concentrations of these hormones are associated with prostate cancer risk. Methods: In this nested case-control study of men in the finasteride arm of the Prostate Cancer Prevention Trial, sex steroid hormones and sex hormone binding globulin were measured at baseline and approximately 3-year posttreatment in 553 prostate cancer cases and 694 controls. Results: Median posttreatment changes in concentrations of 3α-dG, T, E1, and E2 were -73.8%, +10.1%, +11.2%, and +7.5% (all P <0.001), respectively. Neither the pre- nor posttreatment concentrations of 3α-dG, nor its change, were associated with risk. Pretreatment, high concentrations of E1 and low concentrations of T were associated with increased cancer risk [OR; 95% confidence interval (CI) quartile 4 vs. 1: 1.38 (0.99-1.93) Ptrend = 0.03; 0.64 (0.43-0.93) Ptrend = 0.07, respectively]. Posttreatment, high concentrations of both E1 and E2 were associated with increased cancer risk [OR; 95% CI quartile 4 vs. 1: 1.54 (1.09-2.17) Ptrend = 0.03; 1.49 (1.07-2.07) Ptrend = 0.02, respectively]. Conclusions: Among finasteride-treated men, concentrations of 3α-dG were not associated with total or Gleason grades 2 to 6, 7 to 10, or 8 to 10 cancer. High serum estrogens may increase cancer risk when intraprostatic DHT is pharmacologically lowered. Impact: Low posttreatment serum estrogens may identify men more likely to benefit from use of finasteride to prevent prostate cancer.

Original languageEnglish (US)
Pages (from-to)1823-1832
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume21
Issue number10
DOIs
StatePublished - Oct 2012

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Androstane-3,17-diol
Finasteride
Gonadal Steroid Hormones
Prostatic Neoplasms
Glucuronides
Serum
Dihydrotestosterone
Neoplasms
Estrogens
Confidence Intervals
Sex Hormone-Binding Globulin
Estrone
Testosterone
Case-Control Studies
Estradiol
Oxidoreductases
androstane-3,17-diol glucuronide
Hormones

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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Associations of serum sex steroid hormone and 5α-androstane-3α, 17β-diol glucuronide concentrations with prostate cancer risk among men treated with finasteride. / Kristal, Alan R.; Till, Cathee; Tangen, Catherine M.; Goodman, Phyllis J.; Neuhouser, Marian L.; Stanczyk, Frank Z.; Chu, Lisa W.; Patel, Sherfaraz K.; Thompson, Ian M.; Reichardt, Juergen K.; Hoque, Ashraful; Platz, Elizabeth A; Figg, William D.; Van Bokhoven, Adrie; Lippman, Scott M.; Hsing, Ann W.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 21, No. 10, 10.2012, p. 1823-1832.

Research output: Contribution to journalArticle

Kristal, AR, Till, C, Tangen, CM, Goodman, PJ, Neuhouser, ML, Stanczyk, FZ, Chu, LW, Patel, SK, Thompson, IM, Reichardt, JK, Hoque, A, Platz, EA, Figg, WD, Van Bokhoven, A, Lippman, SM & Hsing, AW 2012, 'Associations of serum sex steroid hormone and 5α-androstane-3α, 17β-diol glucuronide concentrations with prostate cancer risk among men treated with finasteride', Cancer Epidemiology Biomarkers and Prevention, vol. 21, no. 10, pp. 1823-1832. https://doi.org/10.1158/1055-9965.EPI-12-0695
Kristal, Alan R. ; Till, Cathee ; Tangen, Catherine M. ; Goodman, Phyllis J. ; Neuhouser, Marian L. ; Stanczyk, Frank Z. ; Chu, Lisa W. ; Patel, Sherfaraz K. ; Thompson, Ian M. ; Reichardt, Juergen K. ; Hoque, Ashraful ; Platz, Elizabeth A ; Figg, William D. ; Van Bokhoven, Adrie ; Lippman, Scott M. ; Hsing, Ann W. / Associations of serum sex steroid hormone and 5α-androstane-3α, 17β-diol glucuronide concentrations with prostate cancer risk among men treated with finasteride. In: Cancer Epidemiology Biomarkers and Prevention. 2012 ; Vol. 21, No. 10. pp. 1823-1832.
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title = "Associations of serum sex steroid hormone and 5α-androstane-3α, 17β-diol glucuronide concentrations with prostate cancer risk among men treated with finasteride",
abstract = "Background: Finasteride, an inhibitor of 5α-reductase (type II), lowers intraprostatic dihydrotestosterone (DHT), which is reflected in serum as reduced 5α-androstane-3α,17β-diol glucuronide (3α-dG). It also modestly increases serum testosterone (T), estrone (E1), and estradiol (E2). In this altered hormonal milieu, it is unknown whether serum concentrations of these hormones are associated with prostate cancer risk. Methods: In this nested case-control study of men in the finasteride arm of the Prostate Cancer Prevention Trial, sex steroid hormones and sex hormone binding globulin were measured at baseline and approximately 3-year posttreatment in 553 prostate cancer cases and 694 controls. Results: Median posttreatment changes in concentrations of 3α-dG, T, E1, and E2 were -73.8{\%}, +10.1{\%}, +11.2{\%}, and +7.5{\%} (all P <0.001), respectively. Neither the pre- nor posttreatment concentrations of 3α-dG, nor its change, were associated with risk. Pretreatment, high concentrations of E1 and low concentrations of T were associated with increased cancer risk [OR; 95{\%} confidence interval (CI) quartile 4 vs. 1: 1.38 (0.99-1.93) Ptrend = 0.03; 0.64 (0.43-0.93) Ptrend = 0.07, respectively]. Posttreatment, high concentrations of both E1 and E2 were associated with increased cancer risk [OR; 95{\%} CI quartile 4 vs. 1: 1.54 (1.09-2.17) Ptrend = 0.03; 1.49 (1.07-2.07) Ptrend = 0.02, respectively]. Conclusions: Among finasteride-treated men, concentrations of 3α-dG were not associated with total or Gleason grades 2 to 6, 7 to 10, or 8 to 10 cancer. High serum estrogens may increase cancer risk when intraprostatic DHT is pharmacologically lowered. Impact: Low posttreatment serum estrogens may identify men more likely to benefit from use of finasteride to prevent prostate cancer.",
author = "Kristal, {Alan R.} and Cathee Till and Tangen, {Catherine M.} and Goodman, {Phyllis J.} and Neuhouser, {Marian L.} and Stanczyk, {Frank Z.} and Chu, {Lisa W.} and Patel, {Sherfaraz K.} and Thompson, {Ian M.} and Reichardt, {Juergen K.} and Ashraful Hoque and Platz, {Elizabeth A} and Figg, {William D.} and {Van Bokhoven}, Adrie and Lippman, {Scott M.} and Hsing, {Ann W.}",
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T1 - Associations of serum sex steroid hormone and 5α-androstane-3α, 17β-diol glucuronide concentrations with prostate cancer risk among men treated with finasteride

AU - Kristal, Alan R.

AU - Till, Cathee

AU - Tangen, Catherine M.

AU - Goodman, Phyllis J.

AU - Neuhouser, Marian L.

AU - Stanczyk, Frank Z.

AU - Chu, Lisa W.

AU - Patel, Sherfaraz K.

AU - Thompson, Ian M.

AU - Reichardt, Juergen K.

AU - Hoque, Ashraful

AU - Platz, Elizabeth A

AU - Figg, William D.

AU - Van Bokhoven, Adrie

AU - Lippman, Scott M.

AU - Hsing, Ann W.

PY - 2012/10

Y1 - 2012/10

N2 - Background: Finasteride, an inhibitor of 5α-reductase (type II), lowers intraprostatic dihydrotestosterone (DHT), which is reflected in serum as reduced 5α-androstane-3α,17β-diol glucuronide (3α-dG). It also modestly increases serum testosterone (T), estrone (E1), and estradiol (E2). In this altered hormonal milieu, it is unknown whether serum concentrations of these hormones are associated with prostate cancer risk. Methods: In this nested case-control study of men in the finasteride arm of the Prostate Cancer Prevention Trial, sex steroid hormones and sex hormone binding globulin were measured at baseline and approximately 3-year posttreatment in 553 prostate cancer cases and 694 controls. Results: Median posttreatment changes in concentrations of 3α-dG, T, E1, and E2 were -73.8%, +10.1%, +11.2%, and +7.5% (all P <0.001), respectively. Neither the pre- nor posttreatment concentrations of 3α-dG, nor its change, were associated with risk. Pretreatment, high concentrations of E1 and low concentrations of T were associated with increased cancer risk [OR; 95% confidence interval (CI) quartile 4 vs. 1: 1.38 (0.99-1.93) Ptrend = 0.03; 0.64 (0.43-0.93) Ptrend = 0.07, respectively]. Posttreatment, high concentrations of both E1 and E2 were associated with increased cancer risk [OR; 95% CI quartile 4 vs. 1: 1.54 (1.09-2.17) Ptrend = 0.03; 1.49 (1.07-2.07) Ptrend = 0.02, respectively]. Conclusions: Among finasteride-treated men, concentrations of 3α-dG were not associated with total or Gleason grades 2 to 6, 7 to 10, or 8 to 10 cancer. High serum estrogens may increase cancer risk when intraprostatic DHT is pharmacologically lowered. Impact: Low posttreatment serum estrogens may identify men more likely to benefit from use of finasteride to prevent prostate cancer.

AB - Background: Finasteride, an inhibitor of 5α-reductase (type II), lowers intraprostatic dihydrotestosterone (DHT), which is reflected in serum as reduced 5α-androstane-3α,17β-diol glucuronide (3α-dG). It also modestly increases serum testosterone (T), estrone (E1), and estradiol (E2). In this altered hormonal milieu, it is unknown whether serum concentrations of these hormones are associated with prostate cancer risk. Methods: In this nested case-control study of men in the finasteride arm of the Prostate Cancer Prevention Trial, sex steroid hormones and sex hormone binding globulin were measured at baseline and approximately 3-year posttreatment in 553 prostate cancer cases and 694 controls. Results: Median posttreatment changes in concentrations of 3α-dG, T, E1, and E2 were -73.8%, +10.1%, +11.2%, and +7.5% (all P <0.001), respectively. Neither the pre- nor posttreatment concentrations of 3α-dG, nor its change, were associated with risk. Pretreatment, high concentrations of E1 and low concentrations of T were associated with increased cancer risk [OR; 95% confidence interval (CI) quartile 4 vs. 1: 1.38 (0.99-1.93) Ptrend = 0.03; 0.64 (0.43-0.93) Ptrend = 0.07, respectively]. Posttreatment, high concentrations of both E1 and E2 were associated with increased cancer risk [OR; 95% CI quartile 4 vs. 1: 1.54 (1.09-2.17) Ptrend = 0.03; 1.49 (1.07-2.07) Ptrend = 0.02, respectively]. Conclusions: Among finasteride-treated men, concentrations of 3α-dG were not associated with total or Gleason grades 2 to 6, 7 to 10, or 8 to 10 cancer. High serum estrogens may increase cancer risk when intraprostatic DHT is pharmacologically lowered. Impact: Low posttreatment serum estrogens may identify men more likely to benefit from use of finasteride to prevent prostate cancer.

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