5-alpha-reductase inhibitors for prostate cancer prevention

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Abstract
Five‐alpha‐reductase inhibitors (5ARI) are frequently used to treat bothersome lower urinary tract symptoms associated with benign prostatic hyperplasia and male androgenic alopecia. They have potential as chemopreventive agents. We sought to estimate the effectiveness and harms of 5ARI in preventing prostate cancer. MEDLINE, PreMEDLINE, and the Cochrane Collaboration Library were searched through April 2007 to identify randomized trials. For prostate cancer outcomes we included randomized controlled trials of at least 1 year in duration published after 1984. For non‐prostate cancer outcomes, randomized trials were included if: they were at least 6 months in duration published after 1999. The primary outcome was prostate cancer period‐prevalence "for‐cause." "For‐cause" was defined as prostate cancer clinically detected based on symptoms, an abnormal digital rectal exam, or detected as a result of an abnormal prostate specific antigen value. Trials were categorized as long (> 2 year), mid (1 to 2 years) and short (< 1 year) term. Nine trials reported prostate cancer period‐prevalence. Three trials using finasteride lasted four years or longer but only one (the Prostate Cancer Prevention Trial) was specifically designed to assess the impact of 5ARI on prostate cancer period‐prevalence. The mean age of enrollees was 64.6 years, 91% were white, mean PSA was 2.1 ng/mL. For‐cause prostate cancers comprised 54% of all cancers detected. Finasteride was associated with a 26% relative risk reduction in prostate cancers detected for‐cause among all randomized subjects (relative risk 0.74 (95% CI 0.67 to 0.83); absolute risk reduction = 1.4% (3.5% versus 4.9%). Six trials assessed prostate cancers detected overall with a pooled 26% relative reduction favoring 5ARI (relative risk 0.74 (95% CI 0.55 to1.00); 2.9% absolute reduction (6.3% versus 9.2%). Reductions were observed regardless of age, race or family history of prostate cancer but not among men with baseline PSA > 4.0 ng/mL. A greater number of high Gleason score tumors (7 to 10 or 8 to 10) occurred in men on finasteride in the PCPT. Impaired sexual or erectile function or endocrine effects were more common with finasteride than placebo. Five‐alpha‐reductase inhibitors reduce prostate cancer risk but may increase the risk of high‐grade disease in men who are undergoing regular screening for prostate cancer using prostate specific antigen and digital rectal examination. Effects are consistent across race, family history and age and possibly 5ARI but were limited to men with baseline PSA values < 4.0 ng/mL. The impact of 5ARI on absolute or relative rates of prostate cancer in men who are not being regularly screened is not clear. Information is inadequate to assess the impact of 5ARI on mortality. 5α還原酉每抑制劑對前列腺癌的預防 5α還原酉每抑制劑 (5ARI) 常用來治療和惱人的前列腺肥大相關的下泌尿道症狀以及雄性禿，可望成為化學預防性藥物。 我們評估5ARI在前列腺癌預防上之效用和毒性。 使用MEDLINE，PreMEDLINE，和the Cochrane Collaboration搜尋2007年4月至今的隨機對照臨床試驗。 針對前列腺癌的預後指標，我們收集於1984年之後發表，至少進行一年的隨機對照試驗。對於非前列腺癌的預後指標，則是收集1999年以後出版，至少進行6個月的隨機對照臨床試驗。 主要評估結果為前列腺癌某一時期，因各種原因 (forcause) 而診斷之前列腺癌盛行率。「原因」意指因有臨床症狀，肛門指診異常或前列腺特異抗原 (prostate specific antigen) 值不正常，而被診斷出患有前列腺癌。試驗分為長期 (> 2年)，中期 (1−2年) 和短期 ( 4.0 ng/ml的男子。在PCPT試驗，使用finasteride的男性有較高惡性腫瘤 (Gleason score 7−10或8−10) 的機會，finasteride組中，性功能、勃起障礙或是內分泌影響也比安慰劑組較多。 對於定期接受前列腺特異抗原檢測及肛門指診篩檢的男性，5ARI可減少前列腺癌機率，但也會增加罹患較高惡性度癌的風險。這種效果僅限於受試前PSA< 4.0 ng/ml之男性，且不受種族、家族病史、年齡甚或不同的5ARI等因素影響。對於未接受定期篩檢之男性，5ARI對於罹患前列腺癌相對或絕對風險的影響不明。缺乏足夠資料評估5ARI對死亡率的影響。 本摘要由臺灣大學附設醫院王禎薇翻譯。 此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。 5ARI，如finasteride或dutasteride，能降低定期接受前列腺癌篩檢之男性罹患前列腺癌之風險。5ARI有可能成為化學預防劑。在不同種族、年齡組 (年齡65歲或以上和較年輕組) 以及家族病史族群中，前列腺癌減少比率相似。只有PSA基準值小於4.0 ng /...