Endometriosis is a gynaecological disease characterized by the presence of ectopic endometrial tissue that affects women during their reproductive years, having a strong impact on their lives, fertility and healthcare costs. The aetiology remains largely unknown, but current evidence suggests that it is multi-causal and oestrogen-dependent. Many epidemiologic studies have explored associations between organochlorine chemicals (OCCs) and endometriosis, but the findings are inconsistent. A systematic review (SR) and meta-analysis were conducted to gather and synthesize all the available evidence from human epidemiological studies about the associations between OCCs and endometriosis. The searches were conducted in PubMed and Web of Science in June 2016 with a final follow-up in August 2018. Only human epidemiological studies were considered, independent of participant age, body mass index or life-stage. Studies reporting individual measures of exposure to OCCs were included, considering but not limited to polychlorinated dibenzodioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), or organochlorine pesticides (OCPs). The primary health outcome was presence of endometriosis, including all sub-types. Eligibility criteria excluded articles not written in English, conference papers, reviews and studies with overlapping information. A SR protocol pre-registered at PROSPERO was applied in duplicate to gather and extract all eligible original papers from PUBMED and Web of Science databases. Odds ratios were pooled using the inverse variance method for random effects meta-analysis for each group of OCCs. Risk of bias was assessed using the National Toxicology Program/Office of Health Assessment and Translation (NTP/OHAT) Risk of Bias Rating Tool for Human and Animal Studies adapted to the review question. The confidence in the body of evidence and related level of evidence was measured by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) based NTP/OHAT framework. The results were structured and presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Of the 51 studies retained for the full-text screening, 17 provided effect sizes and metrics sufficient for pooling estimates through meta-analysis. The overall odds ratios and 95% confidence intervals were 1.65 (1.14; 2.39) for dioxins (n = 10), 1.70 (1.20; 2.39) for PCBs (n = 9), and 1.23 (1.13; 1.36) for OCPs (n = 5). Despite being statistically significant, these estimates should be considered with caution given the notable heterogeneity and small estimated effect size. Misclassification of exposure, due to varying laboratory detection rate capabilities, and disease status, due to varying definitions of endometriosis, were identified as major sources of uncertainty. The level of evidence was considered to be "moderate" with "serious" risk of bias according the NTP/OHAT criteria, supporting the need for further well-designed epidemiological research to fill lingering data gaps. Given the complexity of endometriosis and lack of known biomarkers suitable for population-based research, carefully designed observational studies play an important role in better understanding the aetiology of endometriosis, as will evolving mixture modeling approaches capable of handling various environmental chemical exposures. Attention to critical windows of exposure will shed further light on the possible developmental origin of endometriosis. Considering the high economic and societal cost associated with endometriosis, further research on this field is urged. CRD42018080956.

Many studies have demonstrated a link between pelvic floor myofascial syndromes and chronic pelvic pain. Botulinum toxin has been extensively used for several years in the field of pain, especially due to its action on muscle spasm. However, the efficacy of botulinum toxin in the context of chronic pelvic pain remains controversial. This multicentre, randomized, controlled, double-blind study was designed to compare the efficacy of botulinum toxin and local anaesthetic (LA) injection versus LA injection alone for pelvic floor myofascial syndrome and chronic pelvic pain. According to the number of painful trigger points detected on physical examination, patients received from 1 to 4 injections of botulinum toxin with LA (BTX) or LA alone. The primary endpoint was Patient Global Impression of Improvement (PGI-I) score on day 60 after infiltration. Secondary endpoints were pain intensity, number of painful trigger points on palpation, analgesic drug consumption and quality of life. We included 80 patients, 40 in each group. This study failed to demonstrate a significant difference between the 2 groups on day 60 in the primary endpoint or secondary endpoints (PGI-I score≤2=20% [LA] versus 27.5% [BTX], P=0.43). However, both groups showed significant alleviation of global pain. This study does not justify the use of botulinum toxin in the context of chronic pelvic pain with myofascial syndrome but does justify muscle injections with LA alone. ClinicalTrials.gov: NCT01967524.

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. 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). 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. 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. 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 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. 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. 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.