CUNY School of Public Health at Hunter College, 2180 Third Avenue, New York, NY 10035, USA.
BMC Med. 2013 Feb 28;11:57. doi: 10.1186/1741-7015-11-57.
Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates more than other lipid-modulating drugs, although evidence from randomized controlled trials also suggests that statins unexpectedly increase the risk of diabetes and improve immune function. Physiologically, statins would be expected to lower androgens because statins inhibit production of the substrate for the local synthesis of androgens and statins' pleiotropic effects are somewhat similar to the physiological effects of lowering testosterone, so we hypothesized that statins lower testosterone.
A meta-analysis of placebo-controlled randomized trials of statins to test the a priori hypothesis that statins lower testosterone. We searched the PubMed, Medline and ISI Web of Science databases until the end of 2011, using '(Testosterone OR androgen) AND (CS-514 OR statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR rosuvastatin OR pravastatin)' restricted to randomized controlled trials in English, supplemented by a bibliographic search. We included studies with durations of 2+ weeks reporting changes in testosterone. Two reviewers independently searched, selected and assessed study quality. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting.
Of the 29 studies identified 11 were eligible. In 5 homogenous trials of 501 men, mainly middle aged with hypercholesterolemia, statins lowered testosterone by -0.66 nmol/l (95% confidence interval (CI) -0.14 to -1.18). In 6 heterogeneous trials of 368 young women with polycystic ovary syndrome, statins lowered testosterone by -0.40 nmol/l (95% CI -0.05 to -0.75). Overall statins lowered testosterone by -0.44 nmol/l (95% CI -0.75 to -0.13).
Statins may partially operate by lowering testosterone. Whether this is a detrimental side effect or mode of action warrants investigation given the potential implications for drug development and prevention of non-communicable chronic diseases. See commentary article here http://www.biomedcentral.com/1741-7015/11/58.
他汀类药物广泛用于心血管疾病的预防。他汀类药物降低死亡率的效果优于其他调脂药物，尽管随机对照试验的证据也表明他汀类药物意外增加了糖尿病的风险并改善了免疫功能。从生理学角度来看，他汀类药物应该会降低雄激素水平，因为他汀类药物抑制了雄激素局部合成的底物的产生，并且他汀类药物的多效性作用与降低睾酮的生理作用有些相似，所以我们假设他汀类药物降低了睾酮水平。
我们对他汀类药物的安慰剂对照随机试验进行了荟萃分析，以检验他汀类药物降低睾酮的先验假设。我们使用 '(Testosterone OR androgen) AND (CS-514 OR statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR rosuvastatin OR pravastatin)' 限制在英语的随机对照试验中，在 PubMed、Medline 和 ISI Web of Science 数据库中进行了搜索，直到 2011 年底，并通过参考文献搜索进行了补充。我们纳入了持续时间为 2 周以上、报告睾酮变化的研究。两位评审员独立搜索、选择和评估研究质量。两位统计学家独立提取和分析数据，使用随机或固定效应模型，根据需要使用倒数方差加权。
在确定的 29 项研究中，有 11 项符合条件。在 5 项针对 501 名主要为中年高胆固醇血症男性的同质试验中，他汀类药物使睾酮降低了-0.66 nmol/l（95%置信区间（CI）-0.14 至-1.18）。在 6 项针对 368 名多囊卵巢综合征年轻女性的异质试验中，他汀类药物使睾酮降低了-0.40 nmol/l（95% CI -0.05 至-0.75）。总体而言，他汀类药物使睾酮降低了-0.44 nmol/l（95% CI -0.75 至-0.13）。
他汀类药物可能通过降低睾酮来发挥部分作用。鉴于其对药物开发和预防非传染性慢性疾病的潜在影响，这种作用是否是一种有害的副作用或作用模式值得进一步研究。请在此处查看评论文章：http://www.biomedcentral.com/1741-7015/11/58。
