Hamilton Robert J, Goldberg Kenneth C, Platz Elizabeth A, Freedland Stephen J
Division of Urologic Surgery, Department of Surgery, and the Duke Prostate Center, Duke University School of Medicine, Durham, NC 27710, USA.
J Natl Cancer Inst. 2008 Nov 5;100(21):1511-8. doi: 10.1093/jnci/djn362. Epub 2008 Oct 28.
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.
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.
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 > or =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.
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.
近期数据表明，使用他汀类药物可能与晚期前列腺癌风险降低有关。然而，他汀类药物对前列腺特异性抗原（PSA）水平的影响以及这可能对前列腺癌诊断产生何种潜在影响尚不清楚。
我们对1214名男性进行了一项纵向研究，这些男性于1990年至2006年期间在达勒姆退伍军人事务医疗中心被开具他汀类药物处方，他们没有前列腺癌，未接受过前列腺手术，也未服用过已知会改变雄激素水平的药物，并且在开始服用他汀类药物前2年内至少有一次PSA值，开始服用他汀类药物后1年内至少有一次PSA值。使用Wilcoxon符号秩检验将他汀类药物治疗前后PSA的变化作为连续变量进行分析。使用多元线性回归分析PSA变化与胆固醇参数（低密度脂蛋白[LDL]、高密度脂蛋白[HDL]和总胆固醇）变化之间的关联。所有统计检验均为双侧检验。
开始服用他汀类药物时的平均（标准差）年龄为60.3（8.3）岁；他汀类药物治疗前PSA浓度中位数为0.9（1.9）ng/mL；他汀类药物治疗前LDL胆固醇浓度平均值为144（34）mg/dL。开始服用他汀类药物后，LDL中位数下降27.5%，PSA中位数下降4.1%（两项比较P均<0.001）。PSA浓度变化与他汀类药物剂量和LDL水平变化密切相关。开始服用他汀类药物后，LDL每降低10%，PSA水平下降1.64（95%置信区间[CI]=0.64%至2.65%，p=0.001）。在最有可能考虑进行前列腺活检的男性（他汀类药物治疗前PSA水平≥2.5 ng/mL，n=188）中，开始服用他汀类药物后LDL下降>41%（最高四分位数）的男性血清PSA下降了17.4%（95%CI=10.0%至24.9%）。
开始他汀类药物治疗后，PSA水平在统计学上有显著下降。在LDL下降幅度最大的男性以及PSA水平使其成为前列腺活检候选者的男性中，这种下降最为明显。通过降低PSA水平，他汀类药物可能会使癌症检测变得复杂，尽管需要进一步研究来量化这种影响的临床意义。
