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 (E(1)), and estradiol (E(2)). 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, E(1), and E(2) 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 E(1) 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) P(trend) = 0.03; 0.64 (0.43-0.93) P(trend) = 0.07, respectively]. Posttreatment, high concentrations of both E(1) and E(2) were associated with increased cancer risk [OR; 95% CI quartile 4 vs. 1: 1.54 (1.09-2.17) P(trend) = 0.03; 1.49 (1.07-2.07) P(trend) = 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.

• Authors: 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
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 21 Issue 10 Pg. 1823-32 (Oct 2012) ISSN: 1538-7755 [Electronic] United States
• PMID: 22879203 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
• Copyright: 2012 AACR

Chemical References

• 5-alpha Reductase Inhibitors
• Glucuronides
• Gonadal Steroid Hormones
• Sex Hormone-Binding Globulin
• Androstane-3,17-diol
• Finasteride

Topics

• 5-alpha Reductase Inhibitors (therapeutic use)
• Aged
• Androstane-3,17-diol (blood)
• Case-Control Studies
• Finasteride (therapeutic use)
• Glucuronides (blood)
• Gonadal Steroid Hormones (blood)
• Humans
• Male
• Middle Aged
• Prostatic Neoplasms (blood, etiology, prevention & control)
• Risk
• Sex Hormone-Binding Globulin (analysis)