Associations between exposure to organochlorine chemicals and endometriosis in experimental studies: A systematic review protocol

Environ Int. 2019 Mar;124:400-407. doi: 10.1016/j.envint.2018.12.063. Epub 2019 Jan 22.


Background: Endometriosis is a hormone-dependent gynaecological disease characterised by the presence and growth of endometrial tissues outside of the uterus. There is growing experimental evidence that suggests environmental endocrine disrupting chemicals, specifically organochlorine chemicals (OCCs), may play a role in the pathogenesis of endometriosis, but to date, there are no studies attempting to gather and synthesise the published literature systematically.

Objectives: The main objective of this SR is to evaluate the associations between the exposure to OCCs and endometriosis in experimental models (in vivo and in vitro).

Methods: The SR framework has been developed following the guidelines established in National Toxicology Program/ Office of Health Assessment and Translation (NTP/OHAT) Handbook for Conducting a Literature-Based Health Assessment, which provides a standardised methodology to implement the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to environmental health assessments. The review process will be managed and documented through HAWC, an open-source content management system, to guarantee transparency.

Eligibility criteria: Only experimental studies, in vivo, ex vivo or in vitro, exploring associations between controlled exposures to OCCs and endometriosis and related outcomes will be included. Eligible studies will include peer reviewed articles of any publication date which are sources of primary data. Only studies published in English will be considered.

Information sources: We will apply the search strings to the scientific literature databases NCBI PubMed, Web of Science and SCOPUS. Manual searches will be performed through the list of references of included articles.

Data extraction and synthesis or results: Data will be extracted according to a pre-defined set of forms and synthesised in a narrative report. Given sufficient commensurate data, a meta-analysis may also be performed.

Risk of bias: A quality assessment will be performed for in vivo and in vitro studies using the NTP/OHAT Risk of Bias Rating Tool for Human and Animal Studies.

Level of evidence rating: Following a comprehensive assessment of the quality of evidence for both in vivo and in vitro studies, a confidence rating will be assigned to the body of literature and subsequently translated into a rating on the level of evidence (high, moderate, low, or inadequate) regarding the research question. Systematic review registration: PROSPERO CRD42018102618.

Keywords: Dioxins; Endocrine disrupting chemicals; Endometriosis; In vitro; In vivo; Organochlorine; Systematic review.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Animals
  • Endocrine Disruptors / toxicity*
  • Endometriosis / chemically induced*
  • Female
  • Humans
  • Hydrocarbons, Chlorinated / toxicity*
  • Research Design
  • Risk Assessment
  • Systematic Reviews as Topic*


  • Endocrine Disruptors
  • Hydrocarbons, Chlorinated