Assessment of Atorvastatin Effectiveness on Serum PSA Level in Hypercholesterolemic Males
The previous large retrospective studies demonstrated that treatment with Statins reduces both the incidence of prostate cancer by 50% and serum Prostate Specific Antigen (PSA) level up to 40%. However the main problem in those studies was the absence of control groups of men with hypercholesterolemia without Statin treatment. We performed a small prospective controlled clinical trial to assess the influence of the treatment with Atorvastatin on serum PSA in men with hypercholesterolemia referred to our educational and treatment center from October 2007 to March 2008. In this study, among the newly diagnosed males with hypercholesterolemia (LDL > 130 mg/dl), 40 patients with LDL more than 190 mg/dl were selected as a case group and were treated with Atorvastatin (20 mg/day). Among the same population and in the same period, another 40 patients with LDL between 130 and 190 mg/dl were selected as first control group and were treated only with low fat diet. Another 40 patients with normal serum cholesterol and without any treatment were selected as second control group. The lipid profile and serum PSA level of patients of all groups were tested at the first and third months after the therapy. After completion of data, the mean serum lipids and PSA level were measured in both visits and compared with each other by paired t-test. Also the mean PSA change in two visits between three groups was compared by ANOVA and Tukey HSD test. There was not any significant difference in mean baseline PSA between hypercholesterolemic and normocholesterolemic patients (P=0.547). In case group, mean PSA and LDL was reduced by 14.1% (P=0.0001) and 30% (P=0.0001) respectively by second visit. In first control group, mean PSA was not changed significantly (P=0.337), whereas mean LDL in this group was reduced by 9.6% (P= 0.0001). Similarly in the second control group mean PSA was not changed significantly (P=0.309) by second visit. In addition, mean change of PSA in case group was compared with first and second control groups that was significantly different (P=0.0001) whereas mean change of PSA between two control groups was not significantly different (P=0.615). The results of this study showed that: 1) Short term treatment with Atorvastatin can reduce serum PSA level, and 2) This reduction is more likely to be due to direct effect and is not related to lowering serum cholesterol levels. Thus, if results of this study are confirmed by large prospective randomized clinical trials with longer follow up period, it will be possible that Atorvastatin could be used in long term as a safe chemoprophylactic agent against prostate cancer in high risk patients.
Klein EA, Platz E., Thompson I. Epidemiology, etiology and prevention of prostate cancer. In: Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA, editors. Campbell- Walsh Urology. 9th ed. Philadelphia, Pa: Saunders Elsevier; 2007. p. 2854-63.
Eastham JA, Scardino PT. Expectant management of prostate cancer. In: Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA, editors. Campbell-Walsh Urology. 9th ed. Philadelphia, Pa: Saunders Elsevier; 2007. p. 2947.
Gretzer MB, Partin AW. Prostate cancer tumor markers. In: Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA, editors. Campbell-Walsh Urology. 9th ed. Philadelphia, Pa: Saunders Elsevier; 2007. p. 2896-907.
Bernini F, Poli A, Paoletti R. Safety of HMG-CoA reductase inhibitors: focus on atorvastatin. Cardiovasc Drugs Ther 2001;15(3):211-8.
Stark WW Jr, Blaskovich MA, Johnson BA, Qian Y, Vasudevan A, Pitt B, Hamilton AD, Sebti SM, Davies P. Inhibiting geranylgeranylation blocks growth andpromotes apoptosis in pulmonary vascular smooth muscle cells. Am J Physiol 1998;275(1 Pt 1):L55-63.
Buemi M, Allegra A, Senatore M, Marino D, Medici MA, Aloisi C, Di Pasquale G, Corica F. Pro-apoptotic effect of fluvastatin on human smooth muscle cells. Eur JPharmacol 1999;370(2):201-3.
Ukomadu C, Dutta A. Inhibition of cdk2 activating phosphorylation by mevastatin. J Biol Chem 2003;278(7):4840-6.
Shibata MA, Kavanaugh C, Shibata E, Abe H, Nguyen P, Otsuki Y, Trepel JB, Green JE. Comparative effects of lovastatin on mammary and prostate oncogenesis in transgenic mouse models. Carcinogenesis 2003;24(3):453-9.
Park C, Lee I, Kang WK. Lovastatin-induced E2F-1modulation and its effect on prostate cancer cell death. Carcinogenesis 2001;22(10):1727-31.
Ukomadu C, Dutta A. p21-dependent inhibition of colon cancer cell growth by mevastatin is independent of inhibition of G1 cyclin-dependent kinases. J Biol Chem 2003;278(44):43586-94.
Cyrus-David MS, Weinberg A, Thompson T, Kadmon D. The effect of statins on serum prostate specific antigen levels in a cohort of airline pilots: a preliminary report. J Urol 2005;173(6):1923-5.
Platz EA, Leitzmann MF, Visvanathan K, Rimm EB, Stampfer MJ, Willett WC, Giovannucci E. Statin drugs and risk of advanced prostate cancer. J Natl Cancer Inst 2006;98(24):1819-25.
Murtola TJ, Tammela TL, Määttänen L, Huhtala H, Platz EA, Ala-Opas M, Stenman UH, Auvinen A. Prostate cancer and PSA among statin users in the Finnish prostate cancer screening trial. Int J Cancer 2010;127(7):1650-9.
Graaf MR, Beiderbeck AB, Egberts AC, Richel DJ, Guchelaar HJ. The risk of cancer in users of statins. J Clin Oncol 2004;22(12):2388-94.
Newton CJ, Ran G, Xie YX, Bilko D, Burgoyne CH, Adams I, Abidia A, McCollum PT, Atkin SL. Statininduced apoptosis of vascular endothelial cells is blocked by dexamethasone. J Endocrinol 2002;174(1):7-16.
Edwards PA, Ericsson J. Sterols and isoprenoids: signaling molecules derived from the cholesterol biosynthetic pathway. Annu Rev Biochem 1999;68:157-85.
Sinensky M. Recent advances in the study of prenylated proteins. Biochim Biophys Acta 2000;1484(2-3):93-106.
Pérez-Sala D, Mollinedo F. Inhibition of isoprenoid biosynthesis induces apoptosis in human promyelocytic HL-60 cells. Biochem Biophys Res Commun 1994;199(3):1209-15.
Denoyelle C, Vasse M, Körner M, Mishal Z, Ganné F, Vannier JP, Soria J, Soria C. Cerivastatin, an inhibitor of HMG-CoA reductase, inhibits the signaling pathways involved in the invasiveness and metastatic properties of highly invasive breast cancer cell lines: an in vitro study. Carcinogenesis 2001;22(8):1139-48.
Holund B. Latent prostatic cancer in a consecutive autopsy series. Scand J Urol Nephrol 1980;14(1):29-35.
Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA 1993; 269(23): 3015-23