Journal of the National Cancer Institute Advance Access originally published online on October 28, 2008
JNCI Journal of the National Cancer Institute 2008 100(21):1511-1518; doi:10.1093/jnci/djn362
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© The Author 2008. Published by Oxford University Press.
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The Influence of Statin Medications on Prostate-specific Antigen Levels
Affiliations of authors: Division of Urologic Surgery, Department of Surgery, and the Duke Prostate Center (RJH) and Division of General Internal Medicine (KCG), Duke University Medical Center, Durham, NC; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health and James Buchanan Brady Urological Institute and The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions (EAP), Baltimore, MD; Division of Urology, Department of Surgery, University of Toronto, Toronto, ON (RJH); Health Services Research and Development, Veterans Administration Medical Center, Durham, NC (KCG); Section of Urology, Veterans Affairs Medical Center, Durham, NC (RJH, SJF); Division of Urologic Surgery, Departments of Surgery and Pathology, and the Duke Prostate Center, Duke University School of Medicine, Durham, NC (SJF)
Correspondence to: Stephen J. Freedland, MD, Division of Urology, PO Box 2626 DUMC, Duke University School of Medicine, Durham, NC 27710 (e-mail: steve.freedland{at}duke.edu).
Background: Recent data suggest that statin use may be associated with a reduced risk of advanced prostate cancer. However, the influence of statins on prostate-specific antigen (PSA) levels and what effect this could potentially have on prostate cancer diagnosis are unknown.
Methods: We conducted a longitudinal study of 1214 men who were prescribed a statin between 1990 and 2006 at the Durham Veterans Affairs Medical Center who were free of prostate cancer, had not undergone prostate surgery or taken medications known to alter androgen levels and who had at least one PSA value within 2 years before and at least one PSA value within 1 year after starting a statin. The change in PSA from before to after statin treatment was analyzed as a continuous variable using the Wilcoxon signed rank test. The association between change in PSA and change in cholesterol parameters (low-density lipoprotein [LDL], high-density lipoprotein [HDL], and total cholesterol) was analyzed using multivariate linear regression. All statistical tests were two-sided.
Results: Mean (SD) age when starting statins was 60.3 (8.3) years; median prestatin PSA concentration was 0.9 (1.9) ng/mL; and mean prestatin LDL cholesterol concentration was 144 (34) mg/dL. After starting a statin, the median LDL decline was 27.5%, and the median PSA decline was 4.1% (P < .001, for both comparisons). Changes in PSA concentration were strongly associated with statin dose and changes in LDL levels. For every 10% decrease in LDL after starting a statin, PSA levels declined by 1.64 (95 % confidence interval [CI] = 0.64% to 2.65%, p = .001). Among men most likely to be under consideration for prostate biopsy (prestatin PSA levels 
2.5 ng/mL, n = 188), those with >41% declines in LDL (highest quartile) after starting a statin experienced a 17.4% (95% CI = 10.0% to 24.9%) decline in serum PSA.
Conclusions: PSA levels declined by a statistically significant extent after initiation of statin treatment. The reduction was most pronounced among men with the largest LDL declines and those with PSA levels that would make them candidates for prostate biopsy. By lowering PSA levels, statins may complicate cancer detection, although further studies are needed to quantify the clinical significance of this effect.
| CONTEXT AND CAVEATS Prior knowledge Although a number of studies have addressed the association of the use of cholesterol-lowering statins with the risk of prostaste cancer, the influence of statin treatment on prostate-specific antigen (PSA) levels was not known. Study design Longitudinal study of cancer-free men who were taking statins and for whom which pre- and posttreatment PSA test results were available in which the associations of statin use and cholesterol parameters with change in PSA levels were analyzed. Contribution This study indicated that statin use was associated with a small, but statistically significant and dose-dependent, decline in PSA, and that the decline was most pronounced in men with the largest decreases in low-density lipoprotein and those with the highest initial PSA values. Implications By lowering PSA levels, statin might complicate prostate cancer detection. Limitations The effect of statins on the risk of prosate cancer and the clinical significance of their association with a decline in PSA levels remains to be determined. From the Editors
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Manuscript received March 24, 2008; revised August 10, 2008; accepted September 8, 2008.
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J Natl Cancer Inst 2008 100: 1485.
J Natl Cancer Inst 2008 100: 1486.
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