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Adipose to serum ratio and mixtures of persistent organic pollutants in relation to endometriosis: Findings from the ENDO Study.
Endometriosis is an estrogen-dependent disease. Endocrine disrupting chemicals (EDCs) and their mixtures may play an etiologic role.
We evaluated an adipose-to-serum ratio (ASR) of lipophilic EDCs and their mixtures associated with incident endometriosis.
We quantified 13 polychlorinated biphenyl (PCB) congeners, 6 polybrominated diphenyl ether (PBDE) congeners, and 11 organochlorine pesticides (OCPs) in serum and omental fat among women from the ENDO Study (2007-2009) aged 18-44 years diagnosed with (n=190) or without (n=283) surgically-visualized incident endometriosis. Odds ratios (OR) and 95% confidence intervals (CI) between ASR and endometriosis were estimated using logistic regression models adjusted for age (years), body mass index (kg/m2), serum cotinine (ng/ml), and breastfeeding conditional on parity. Bayesian hierarchical models (BHM) compared estimated associations for adipose and ASR to serum. Bayesian kernel machine regression (BKMR) estimated change in latent health and 95% posterior intervals (PI) between chemical mixtures and endometriosis.
Select ASR for estrogenic PCBs and OCPs were associated with an increased odds of an endometriosis diagnosis, but not for anti-estrogenic PCBs or PBDEs. Across all chemicals, BHMs generated ORs that were on average 14% (95% PI: 6%, 22%) higher for adipose and 20% (95% PI: 12%, 29%) higher for ASR in comparison to serum. ORs from BHMs were greater for estrogenic PCBs and OCPs, with no differences for PBDEs. BKMR models comparing the 75th to 25th percentile were moderately associated with endometriosis for estrogenic PCBs [adipose 0.27 (95% PI: 0.18, 0.72) and ASR 0.37 (95% PI: 0.06, 0.80)] and OCPs [adipose 0.17 (95% PI: 0.21, 0.56) and ASR 0.26 (95% PI: 0.05, 0.57)], but not for antiestrogenic PCBs and PBDEs.
ASR added little insight beyond adipose for lipophilic chemicals. BKMR results supported associations between ASR and adipose estrogenic PCB and OCP mixtures and incident endometriosis. These findings underscore the importance of choice of biospecimen and considering mixtures when assessing exposure-disease relationships.
Pollack AZ
,Krall JR
,Kannan K
,Buck Louis GM
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An exposure to endocrine active persistent pollutants and endometriosis - a review of current epidemiological studies.
Widespread exposure to persistent pollutants can disrupt the bodies' natural endocrine functions and contribute to reproductive diseases like endometriosis. In this review, we focus at the relationship between endocrine-disrupting chemicals (EDCs), including metals and trace elements, organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), poly-brominated diphenyl ethers (PBDEs), polychlorinated dibenzodioxin (PCDDs), polychlorinated dibenzofurans (PCDFs), and per- and polyfluoroalkyl substances (PFAS) exposure and risk of endometriosis. Relevant studies from the last 10 years by November 2022 were identified by searching Pubmed, Web of Science, and Scopus. The cohort and case-control studies that reported effect size with 95% confidence intervals (CIs) of EDC exposure and endometriosis were selected. Twenty three articles examining the relationship between endometriosis and exposure to persistent EDCs were considered. Most of the studies indicated association with exposure to persistent chemicals and development of endometriosis. The consistent results were found in case of lead, PCB-28, PCB-138, PCB-153, PCB-180, PCB-201, 1,2,3,7,8 - PeCDD, 2,3,4,7,8 - PeCDF and all described OCPs, showing the increased risk of endometriosis. These results support that exposure to certain EDCs, including OCPs, PCBs, PBBs, PBDEs, PFAS, and lead increase the risk of endometriosis.
Szczęsna D
,Wieczorek K
,Jurewicz J
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Distribution of persistent organic pollutants in serum, omental, and parietal adipose tissue of French women with deep infiltrating endometriosis and circulating versus stored ratio as new marker of exposure.
Several studies have assessed the potential role of environmental chemicals in the onset, growth, and/or physiopathology of endometriosis. However, their contour in terms of considered exposure markers remains limited. The present study aimed to characterize the internal exposure levels of 78 persistent organic pollutants (POPs, including dioxins, polychlorobiphenyls, brominated flame retardants and organochlorine pesticides) in a set of 113 adult French women (45 controls, 68 cases), and to characterize the distribution of these POPs within three biological compartments (omental adipose tissue, parietal adipose tissue, and serum). For all targeted substances, the correlation between the concentrations measured in omental versus parietal adipose tissue was found strongly significant (p<0.0001). An equivalence of the measures performed in parietal and omental adipose tissue was moreover observed with median levels of 6.4 vs. 7.4pg/gl.w. for WHO-TEQ2005 PCDD/F, 4.5 vs. 4.7pg/gl.w. for WHO-TEQ2005 dl-PCB, 137.1 vs. 147.9ng/gl.w. for sum of 6 ndl-PCB, and 2.1 vs. 2.0ng/gl.w. for sum of 7 i-PBDE, respectively. The same observation was made for individual targeted OCs compounds. Significant correlations were also observed between these concentrations determined in adipose tissue and those measured in serum for dioxins (WHO-TEQ2005 PCDD/F=6.1pg/gl.w), PCBs (WHO-TEQ2005 dl-PCB=3.6pg/gl.w., sum of 6 ndl-PCB=81.1ng/gl.w.), and brominated flame-retardants (sum of 7 i-PBDE=0.9ng/gl.w.). The circulating versus stored ratio of some exposure markers (Sum PCDDs, 1,2,3,6,7,8-HxCDF, slightly versus highly chlorinated PCBs ratio, PBDE 99 and PBB 153) was found statistically different for control and case individuals. These extended exposure data from deep infiltrating endometriosis patients are the first ones available for France and give a new insight about the equilibrium of chemicals between storage and circulating compartments that should be further considered as new marker of exposure in the context of exposure-health relationship studies.
Ploteau S
,Antignac JP
,Volteau C
,Marchand P
,Vénisseau A
,Vacher V
,Le Bizec B
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Correlates of Persistent Endocrine-Disrupting Chemical Mixtures among Reproductive-Aged Black Women.
Schildroth S
,Wise LA
,Wesselink AK
,De La Cruz P
,Bethea TN
,Weuve J
,Fruh V
,Botelho JC
,Sjodin A
,Calafat AM
,Baird DD
,Claus Henn B
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Associations between internal exposure levels of persistent organic pollutants in adipose tissue and deep infiltrating endometriosis with or without concurrent ovarian endometrioma.
Endometriosis is a gynaecological disease characterized by the presence of ectopic endometrial tissue. Histologically, it appears as different sub-types, being peritoneal endometriosis, ovarian endometrioma (OvE) and deep infiltrating endometriosis (DIE), which are of major relevance due to their varying clinical presentations. A number of persistent organic pollutants (POPs) have been associated with the onset of endometriosis, yet the overall set of existing studies remains fairly divergent. In this preliminary case-control study we aimed to assess the potential associations between the internal exposure to POPs and the presence of DIE with or without concurrent OvE. Adipose tissue and serum samples were collected from surgically confirmed cases (n=55) and controls (n=44) enrolled during 2013 and 2015 in Pays de la Loire, France. Targeted pollutants (76 historical or more emerging POPs including dioxins, polychlorobiphenyls (PCB), polybrominated diphenyl ethers (PBDEs), polybrominated biphenyls (PBBs), hexabromocyclododecanes (HBCDs) and organochlorine pesticides (OCPs) were quantified by chromatography coupled to mass spectrometry. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated from unconditional logistic regression adjusted for known confounding variables. The results showed significant associations between DIE and adipose tissue levels of 1.2.3.7.8 - PeCDD, OCDF, PCB 105, 114, 118 and 123, PBDE 183, PBB 153, and several OCPs including trans‑nonachlor, cis‑heptachlor epoxide, dieldrin, β-hexachlorocyclohexane and hexachlorobenzene. The largest associations were observed for OCDF followed by cis‑heptachlor epoxide, exhibiting adjusted ORs (95% CI) of 5.42 (2.73-12.85) and 5.36 (2.44-14.84) per 1-SD increase, respectively. The stratified analysis comparing both disease sub-types suggested that adipose tissue exposure markers may be more associated with DIE concurrent with OvE, however these results need to be confirmed in a larger population.
Ploteau S
,Cano-Sancho G
,Volteau C
,Legrand A
,Vénisseau A
,Vacher V
,Marchand P
,Le Bizec B
,Antignac JP
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