Environmental exposures to endocrine disrupting chemicals (EDCs) and their role in endometriosis: a systematic literature review.

Endocrine-related diseases and disorders are on the rise globally. Synthetically produced environmental chemicals (endocrine-disrupting chemicals (EDCs)) mimic hormones like oestrogen and alter signalling pathways. Endometriosis is an oestrogen-dependent condition, affecting 10-15% of women of the reproductive age, and has substantial impacts on the quality of life. The aetiology of endometriosis is believed to be multifactorial, ranging from genetic causes to immunologic dysfunction due to environmental exposure to EDCs. Hence, we undertook a systematic review and investigated the epidemiological evidence for an association between EDCs and the development of endometriosis. We also aimed to assess studies on the relationship between body concentration of EDCs and the severity of endometriosis. Following PRISMA guidelines, a structured search of PubMed, Embase and Scopus was conducted (to July 2018). The included studies analysed the association between one or more EDCs and the prevalence of endometriosis. The types of EDCs, association and outcome, participant characteristics and confounding variables were extracted and analysed. Quality assessment was performed using standard criteria. In total, 29 studies were included. Phthalate esters were positively associated with the prevalence of endometriosis. The majority (71%) of studies revealed a significant association between bisphenol A, organochlorinated environmental pollutants (dioxins, dioxin-like compounds, organochlorinated pesticides, polychlorinated biphenyls) and the prevalence of endometriosis. A positive association between copper, chromium and prevalence of endometriosis was demonstrated in one study only. Cadmium, lead and mercury were not associated with the prevalence of endometriosis. There were conflicting results for the association between nickel and endometriosis. The relationship of EDCs and severity of endometriosis was not established in the studies. We found some evidence to suggest an association between phthalate esters, bisphenol A, organochlorinated environmental pollutants and the prevalence of endometriosis. Disentangling these exposures from various other factors that affect endometriosis is complex, but an important topic for further research.

Sirohi D ，Al Ramadhani R ，Knibbs LD 《-》

Endocrine disruptors and endometriosis.

Endometriosis is a hormone-dependent inflammatory gynecological disease of reproductive-age women. It is clinically and pathologically characterized by the presence of functional endometrium as heterogeneous lesions outside the uterine cavity. The two major symptoms are chronic pelvic pain and infertility, which profoundly affect women's reproductive health and quality of life. This significant individual and public health concerns underscore the importance of understanding the pathogenesis of endometriosis. The environmental endocrine-disrupting chemicals (EDCs) are exogenous agents that interfere with the synthesis, secretion, transport, signaling, or metabolism of hormones responsible for homeostasis, reproduction, and developmental processes. Endometriosis has been potentially linked to exposure to EDCs. In this review, based on the robust literature search, we have selected four endocrine disruptors (i) polychlorinated biphenyls (PCB)s (ii) dioxins (TCDD) (iii) bisphenol A (BPA) and its analogs and (iv) phthalates to elucidate their critical role in the etiopathogenesis of endometriosis. The epidemiological and experimental data discussed in this review indicate that these four EDCs activate multiple intracellular signaling pathways associated with proinflammation, estrogen, progesterone, prostaglandins, cell survival, apoptosis, migration, invasion, and growth of endometriosis. The available information strongly indicates that environmental exposure to EDCs such as PCBs, dioxins, BPA, and phthalates individually or collectively contribute to the pathophysiology of endometriosis. Further understanding of the molecular mechanisms of how these EDCs establish endometriosis and therapeutic strategies to mitigate the effects of these EDCs in the pathogenesis of endometriosis are timely needed. Moreover, understanding the interactive roles of these EDCs in the pathogenesis of endometriosis will help regulate the exposure to these EDCs in reproductive age women.

Dutta S ，Banu SK ，Arosh JA 《-》

Endocrine disrupting chemicals and endometriosis.

Endometriosis is an estrogen dependent gynecologic disease with lasting implications for many women's fertility, somatic health, and overall quality of life. Growing evidence suggests that endocrine disrupting chemicals (EDCs) may be etiologically involved in the development and severity of disease. We weigh the available human evidence focusing on EDCs and endometriosis, restricting to research that has individually quantified chemical concentrations for women, included a comparison group of unaffected women, and used multivariable analytic techniques. Evidence supporting an environmental etiology for endometriosis includes metals/trace elements, dioxins, and other persistent organic pollutants, as well as nonpersistent chemicals, such as benzophenones and phthalates. To address the equivocal findings for various EDCs, future research directions for filling data gaps include [1] use of integrated clinical and population sampling frameworks allowing for incorporation of new diagnostic modalities; [2] the collection of various biologic media, including target tissues for quantifying exposures; [3] study designs that offer various comparison groups to assess potentially shared etiologies with other gynecologic disorders; and [4] novel laboratory and statistical approaches that fully explore all measured EDCs for the assessment of mixtures and low dose effects and the use of directed acyclic graphs and supporting causal analysis for empirically delineating relationships between EDCs and endometriosis.

Smarr MM ，Kannan K ，Buck Louis GM 《-》

Endocrine disrupting chemicals and breast cancer: a systematic review of epidemiological studies.

Wan MLY ，Co VA ，El-Nezami H 《-》

Plastic-related endocrine disrupting chemicals significantly related to the increased risk of estrogen-dependent diseases in women.

To evaluate the association between exposure to plastic-related endocrine-disrupting chemicals (EDCs), specifically Bisphenol A (BPA), Phthalates, Cadmium, and Lead, and the risk of estrogen-dependent diseases (EDDs) such as polycystic ovary syndrome (PCOS), endometriosis, or endometrial cancer by conducting a meta-analysis of relevant studies. PubMed, Web of Science, and Cochrane Library databases were used for literature retrieval of articles published until the 21st of April 2023. Literature that evaluated the association between BPA, phthalates, cadmium, and/or lead exposure and the risk of PCOS, endometriosis, or endometrial cancer development or exacerbation were included in our analysis. STATA/MP 17.0 was used for all statistical analyses. Overall, 22 articles were included in our meta-analysis with a total of 83,641 subjects all of whom were females aged between 18 and 83 years old. The overall effect size of each study was as follows: endometriosis risk in relation to BPA exposure ES 1.82 (95% CI; 1.50, 2.20). BPA and PCOS risk ES 1.61 (95% CI; 1.39, 1.85). Phthalate metabolites and endometriosis risk; MBP ES 1.07 (95% CI; 0.86, 1.33), MEP ES 1.05 (95% CI; 0.87, 1.28), MEHP ES 1.15 (95% CI; 0.67, 1.98), MBzP ES 0.97 (95% CI; 0.63, 1.49), MEOHP ES 1.87 (95% CI; 1.21, 2.87), and MEHHP ES 1.98 (95% CI; 1.32, 2.98). Cadmium exposure and endometrial cancer risk ES 1.14 (95% CI; 0.92, 1.41). Cadmium exposure and the risk of endometriosis ES 2.54 (95% CI; 1.71, 3.77). Lead exposure and the risk of endometriosis ES 1.74 (95% CI; 1.13, 2.69). Increased serum, urinary, or dietary concentration of MBzP and MEHP in women is significantly associated with endometriosis risk. Increased cadmium concentration is associated with endometrial cancer risk.

Chitakwa N ，Alqudaimi M ，Sultan M ，Wu D ... -  《-》