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American Journal of Epidemiology Advance Access originally published online on October 21, 2008
American Journal of Epidemiology 2008 168(12):1416-1424; doi:10.1093/aje/kwn272
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American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

Serum Steroid and Sex Hormone-Binding Globulin Concentrations and the Risk of Incident Benign Prostatic Hyperplasia: Results From the Prostate Cancer Prevention Trial

Alan R. Kristal, Jeannette M. Schenk, YoonJu Song, Kathryn B. Arnold, Marian L. Neuhouser, Phyllis J. Goodman, Daniel W. Lin, Frank Z. Stanczyk and Ian M. Thompson

Correspondence to Dr. Alan R. Kristal, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-B402, P.O. Box 19024, Seattle, WA 98109-1024 (e-mail: akristal{at}fhcrc.org).

Received for publication February 15, 2008. Accepted for publication July 29, 2008.

The authors conducted a nested case-control study of serum steroid concentrations and risk of benign prostatic hyperplasia (BPH), using data from the placebo arm of the Prostate Cancer Prevention Trial (1993–2003). Incident BPH over 7 years (n = 708) was defined as receipt of treatment, a report of 2 International Prostate Symptom Score (IPSS) values greater than 14, or 2 increases of 5 or more from baseline IPSS values with at least 1 value greater than or equal to 12. Controls (n = 709) were selected from men who reported no BPH treatment or any IPSS greater than 7. Baseline serum was analyzed for testosterone, estradiol, estrone, 5{alpha}-androstane-3{alpha}, 17β-diol-glucuronide, and sex hormone-binding globulin. Covariate-adjusted odds ratios contrasting the highest quartiles with the lowest quartiles of testosterone, estradiol, and testosterone:17β-diol-glucuronide ratio were 0.64 (95% confidence interval (CI): 0.43, 0.95; Ptrend = 0.04), 0.72 (95% CI: 0.53, 0.98; Ptrend = 0.09), and 0.64 (95% CI: 0.46, 0.89; Ptrend = 0.004), respectively. Findings did not differ by age, body mass index, time to BPH endpoint, or type of BPH endpoint. High testosterone levels, estradiol levels, and testosterone:17β-diol-glucuronide ratio are associated with reduced BPH risk, which may reflect decreased activity of 5-{alpha}-reductase. Genetic or environmental factors that affect the activity of 5-{alpha}-reductase may be important in the development of symptomatic BPH.

gonadal steroid hormones; prostatic hyperplasia

Abbreviations: BPH, benign prostatic hyperplasia; CI, confidence interval; IPSS, International Prostate Symptom Score; OR, odds ratio; SHBG, sex hormone-binding globulin


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