BACKGROUND More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders. OBJECTIVE AND RATIONALE The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism. SEARCH METHODS A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data. OUTCOMES The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91-1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p'-DDE, was related to an elevated risk: OR 1.35 (95% CI 1.04-1.74). The data did not indicate that this increased risk was driven by any specific disorder. WIDER IMPLICATIONS The current epidemiological evidence is compatible with a small increased risk of male reproductive disorders following prenatal and postnatal exposure to some persistent environmental chemicals classified as endocrine disruptors but the evidence is limited. Future epidemiological studies may change the weight of the evidence in either direction. No evidence of distortion due to publication bias was found, but exposure-response relationships are not evident. There are insufficient data on rapidly metabolized endocrine disruptors and on specific exposure-outcome relations. A particular data gap is evident with respect to delayed effects on semen quality and testicular cancer. Although high quality epidemiological studies are still sparse, future systematic and transparent reviews may provide pieces of evidence contributing to the narrative and weight of the evidence assessments in the field.

中文翻译：

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流行病学证据将产前和产后暴露与内分泌干扰化学物质与男性生殖疾病联系起来：系统评价和荟萃分析。

背景技术二十多年前，有一种假说认为，暴露于产前和产后早期环境中的异种生物可能破坏内源性激素信号，可能是隐睾症，尿道下裂，精子数量少和睾丸癌的病因。近年来，一些共识性声明和叙述性评论分裂了科学界，并引发了对系统透明评论的呼吁。我们旨在填补男性生殖疾病领域的这一知识空白。目的和理由本研究的目的是系统地综合已发表的有关子宫内或婴儿接触化学物质后隐睾症，尿道下裂，精子数量低和睾丸癌的风险的数据，这些数据已被纳入欧盟委员会的研究范围。第1类破坏内分泌的化学物质的清单，定义为已记录了至少一种完整生物体内因破坏内分泌而产生的不利影响。搜索方法在PubMed和Embase数据库中进行了系统的文献搜索，以查找原始的同行评议论文，以鉴定流行病学研究，该研究报告了感兴趣的结果与通过包括母体血液或尿液，胎盘或脂肪组织在内的生物样本的生化分析记录的暴露之间的关联作为羊膜液，脐带血或母乳；接下来是定量数据的荟萃分析。结果文献检索共获得1314篇参考文献，其中我们鉴定了33篇符合入选标准的论文（28个研究人群）。这些提供了关于持久性有机污染物与快速代谢的化合物（邻苯二甲酸酯和双酚A）与男性生殖疾病之间联系的85个风险估计。所有暴露和结果的总体比值比（OR）为1.11（95％CI为0.91-1.35）。当评估具有足够数据进行所有结果的荟萃分析的四个特定化学亚组时，我们发现暴露于四种化合物之一的p，p'-DDE与升高的风险有关：或1.35（95％CI 1.04- 1.74）。数据没有表明这种增加的风险是由任何特定的疾病引起的。进一步的影响目前的流行病学证据与在产前和产后接触被归类为内分泌干扰物的某些持久性环境化学物质引起的男性生殖疾病风险的小幅增加相吻合，但证据有限。未来的流行病学研究可能会朝着两个方向改变证据的分量。没有发现因出版偏倚而导致失真的证据，但暴露与反应之间的关系并不明显。关于快速代谢的内分泌干扰物和具体的暴露-结果关系，没有足够的数据。在延迟影响精液质量和睾丸癌方面，存在明显的数据缺口。尽管高质量的流行病学研究仍然很少，