Faculty of Science, Charles University, Albertov 6, 128 43 Prague, Czech Republic.
School of Public Health, University of Queensland, 288 Herston Road, 4006 Herston, Queensland, Australia.
Hum Reprod Update. 2020 Apr 15;26(3):412-422. doi: 10.1093/humupd/dmaa002.
Despite its high prevalence and health burden, many aspects of endometriosis remain unclear, including risk factors and the underlying biological mechanisms. Exposures during early life, including in utero, are thought to play an important role in the subsequent onset of the condition. To date, however, much of the evidence from studies on early life exposures and diagnosed endometriosis appears mixed and difficult to assess.
This study aims to provide a systematic review of the epidemiologic evidence on early life factors associated with the subsequent diagnosis of endometriosis. In utero and early life exposures have previously been linked to a range of adult health outcomes, including infertility.
A systematic review of case-control, cross-sectional and cohort studies was conducted using the search terms 'endometriosis'[MeSH] AND ('risk factors'[MeSH] OR 'protective factors'[MeSH]) AND ('in utero', 'fetal', 'neonatal, 'perinatal', 'developmental origins', 'early life', 'childhood' OR 'life course') in Embase, PubMed and Scopus databases. The review included articles published in English until 10 June 2018 with original data from studies with diagnosed endometriosis. The quality of primary studies was evaluated using the Newcastle-Ottawa Scale by both authors independently. Due to the degree of inconsistency in the measurements and study methods, a qualitative assessment of findings was undertaken rather than meta-analysis.
The search retrieved 70 records without duplicates that contained 20 records on human case-control, cross-sectional or cohort studies, from which 11 papers/studies were selected based on their assessment score. The majority of studies found that women born with low birthweight (<2.5 kg or <5.5 lb) were more likely to be diagnosed with endometriosis. For other early life factors, the evidence is mixed or limited, with further research needed on the association of endometriosis with preterm birth, in utero exposure to diethylstilbestrol and to maternal smoking, passive smoking in early life, and infant formula feeding (compared with breastfeeding).
While the weight of evidence points to low birthweight as a risk factor for diagnosis of endometriosis, future research is warranted on this and other key early life exposures where the findings are mixed to provide more robust evidence and for insights on potential causal pathways. Such research, however, needs to address current methodological issues, such as the use of prospective data from large population-based studies, better diagnostic methods to confirm disease free status, more consistent definitions of variables and consideration of potential biological mechanisms to guide the analyses. The improvements will advance the future synthesis of evidence to support clinically relevant risk assessment for a more timely diagnosis and treatment of endometriosis.
尽管子宫内膜异位症的患病率和健康负担很高，但仍有许多方面尚未得到明确，包括危险因素和潜在的生物学机制。人们认为，生命早期的暴露，包括宫内暴露，在随后的疾病发作中起着重要作用。然而，迄今为止，许多关于生命早期暴露与确诊子宫内膜异位症的研究证据似乎相互矛盾，难以评估。
本研究旨在对与子宫内膜异位症后续诊断相关的生命早期因素的流行病学证据进行系统综述。生命早期的宫内和暴露已与一系列成人健康结局相关联，包括不孕。
使用 Embase、PubMed 和 Scopus 数据库中的搜索词“子宫内膜异位症”[MeSH]和（“危险因素”[MeSH]或“保护因素”[MeSH]）和（“宫内”、“胎儿”、“新生儿”、“围产期”、“发育起源”、“生命早期”、“儿童期”或“生命历程”）对病例对照、横断面和队列研究进行系统综述。本综述包括截至 2018 年 6 月 10 日以英语发表的文章，原始数据来自确诊为子宫内膜异位症的研究。两位作者独立使用纽卡斯尔-渥太华量表评估初级研究的质量。由于测量和研究方法的不一致程度，进行了定性评估，而不是荟萃分析。
检索未重复的记录 70 条，其中包含 20 条人类病例对照、横断面或队列研究的记录，根据评估得分，从这些记录中选择了 11 篇论文/研究。大多数研究发现，出生体重低（<2.5 公斤或<5.5 磅）的女性更有可能被诊断为子宫内膜异位症。对于其他生命早期因素，证据相互矛盾或有限，需要进一步研究子宫内膜异位症与早产、宫内暴露于己烯雌酚和母亲吸烟、生命早期被动吸烟以及婴儿配方奶喂养（与母乳喂养相比）之间的关系。
虽然证据的权重表明低出生体重是诊断子宫内膜异位症的一个危险因素，但需要对这一因素和其他关键生命早期暴露进行进一步研究，这些因素的研究结果相互矛盾，需要提供更有力的证据，并深入了解潜在的因果途径。然而，这种研究需要解决当前的方法学问题，例如使用来自大型基于人群的研究的前瞻性数据、更好的诊断方法来确认无疾病状态、更一致的变量定义以及考虑潜在的生物学机制来指导分析。这些改进将促进未来对证据的综合，以支持更具临床意义的风险评估，从而更及时地诊断和治疗子宫内膜异位症。
