Lipophilic Environmental Chemicals and Endometriosis
Lipophilic Environmental Chemicals and Endometriosis
Background An equivocal literature exists regarding the relation between persistent organochlorine pollutants (POPs) and endometriosis in women, with differences attributed to methodologies.
Objectives We assessed the association between POPs and the odds of an endometriosis diagnosis and the consistency of findings by biological medium and study cohort.
Methods Using a matched cohort design, we assembled an operative cohort of women 18–44 years of age undergoing laparoscopy or laparotomy at 14 participating clinical centers from 2007 to 2009 and a population-based cohort matched on age and residence within a 50-mile catchment area of the clinical centers. Endometriosis was defined as visualized disease in the operative cohort and as diagnosed by magnetic resonance imaging in the population cohort. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each POP in relation to an endometriosis diagnosis, with separate models run for each medium (omental fat in the operative cohort, serum in both cohorts) and cohort. Adjusted models included age, body mass index, breast-feeding conditional on parity, cotinine, and lipids.
Results Concentrations were higher in omental fat than in serum for all POPs. In the operative cohort, γ-hexachlorocyclohexane (γ-HCH) was the only POP with a significant positive association with endometriosis [per 1-SD increase in log-transformed γ-HCH: adjusted OR (AOR) = 1.27; 95% CI: 1.01, 1.59]; β-HCH was the only significant predictor in the population cohort (per 1-SD increase in log-transformed β-HCH: AOR = 1.72; 95% CI: 1.09, 2.72).
Conclusions Using a matched cohort design, we found that cohort-specific and biological-medium–specific POPs were associated with endometriosis, underscoring the importance of methodological considerations when interpreting findings.
Endometriosis is a prevalent gynecologic disorder that is characterized by the presence and growth of endometrial tissue in ectopic sites (Giudice 2010). An equivocal body of evidence has emerged regarding the relation between lipophilic persistent organochlorine pollutants (POPs) and endometriosis, following an initial report in primates (Rier et al. 1993), with subsequent experimental evidence (Birnbaum and Cummings 2002), including exposures during sensitive windows of development (Crain et al. 2008). Three of seven studies that focused on dioxins or dioxin-like compounds and endometriosis have observed significantly higher concentrations in women with endometriosis than in those without the condition (Heilier et al. 2005; Mayani et al. 1997; Simsa et al. 2010). In addition, four of nine studies that focused on polychlorinated biphenyls (PCBs) observed similar findings (Gerhard and Runnebaum 1992; Louis et al. 2005; Porpora et al. 2006, 2009). To our knowledge, endometriosis has been significantly associated with only one class of organochlorine pesticides (OCPs): aromatic fungicides (Cooney et al. 2010).
The weighing of available human data is challenging, largely because of the nuances associated with the clinical diagnosis of endometriosis and methodologic practices that affect interpretation. The clinical gold standard remains disease visualized via laparoscopy or by laparotomy [American Society for Reproductive Medicine (ASRM) 2006; Kennedy et al. 2005]. Currently, there is no established noninvasive biomarker for diagnosis (May et al. 2010). Visualization of disease necessitates clinical sampling strategies that may exclude symptomatic women who do not seek care or undergo surgery, which precludes our understanding of endometriosis at the population level. Other widely recognized methodologic practices that affect research findings include convenience-based sampling, self-reported (yes/no) disease, varying modeling practices for parity or breast-feeding history that may reduce internal doses of lipophilic POPs (LaKind et al. 2009), and reliance on serum or plasma in lieu of quantification in fat, the presumed gold standard for lipophilic chemicals (Johnson-Restrepo et al. 2005; Whitcomb et al. 2005). We designed the Endometriosis: Natural History, Diagnosis and Outcomes (ENDO) Study to further delineate the relation between lipophilic POPs and endometriosis.
Abstract and Introduction
Abstract
Background An equivocal literature exists regarding the relation between persistent organochlorine pollutants (POPs) and endometriosis in women, with differences attributed to methodologies.
Objectives We assessed the association between POPs and the odds of an endometriosis diagnosis and the consistency of findings by biological medium and study cohort.
Methods Using a matched cohort design, we assembled an operative cohort of women 18–44 years of age undergoing laparoscopy or laparotomy at 14 participating clinical centers from 2007 to 2009 and a population-based cohort matched on age and residence within a 50-mile catchment area of the clinical centers. Endometriosis was defined as visualized disease in the operative cohort and as diagnosed by magnetic resonance imaging in the population cohort. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each POP in relation to an endometriosis diagnosis, with separate models run for each medium (omental fat in the operative cohort, serum in both cohorts) and cohort. Adjusted models included age, body mass index, breast-feeding conditional on parity, cotinine, and lipids.
Results Concentrations were higher in omental fat than in serum for all POPs. In the operative cohort, γ-hexachlorocyclohexane (γ-HCH) was the only POP with a significant positive association with endometriosis [per 1-SD increase in log-transformed γ-HCH: adjusted OR (AOR) = 1.27; 95% CI: 1.01, 1.59]; β-HCH was the only significant predictor in the population cohort (per 1-SD increase in log-transformed β-HCH: AOR = 1.72; 95% CI: 1.09, 2.72).
Conclusions Using a matched cohort design, we found that cohort-specific and biological-medium–specific POPs were associated with endometriosis, underscoring the importance of methodological considerations when interpreting findings.
Introduction
Endometriosis is a prevalent gynecologic disorder that is characterized by the presence and growth of endometrial tissue in ectopic sites (Giudice 2010). An equivocal body of evidence has emerged regarding the relation between lipophilic persistent organochlorine pollutants (POPs) and endometriosis, following an initial report in primates (Rier et al. 1993), with subsequent experimental evidence (Birnbaum and Cummings 2002), including exposures during sensitive windows of development (Crain et al. 2008). Three of seven studies that focused on dioxins or dioxin-like compounds and endometriosis have observed significantly higher concentrations in women with endometriosis than in those without the condition (Heilier et al. 2005; Mayani et al. 1997; Simsa et al. 2010). In addition, four of nine studies that focused on polychlorinated biphenyls (PCBs) observed similar findings (Gerhard and Runnebaum 1992; Louis et al. 2005; Porpora et al. 2006, 2009). To our knowledge, endometriosis has been significantly associated with only one class of organochlorine pesticides (OCPs): aromatic fungicides (Cooney et al. 2010).
The weighing of available human data is challenging, largely because of the nuances associated with the clinical diagnosis of endometriosis and methodologic practices that affect interpretation. The clinical gold standard remains disease visualized via laparoscopy or by laparotomy [American Society for Reproductive Medicine (ASRM) 2006; Kennedy et al. 2005]. Currently, there is no established noninvasive biomarker for diagnosis (May et al. 2010). Visualization of disease necessitates clinical sampling strategies that may exclude symptomatic women who do not seek care or undergo surgery, which precludes our understanding of endometriosis at the population level. Other widely recognized methodologic practices that affect research findings include convenience-based sampling, self-reported (yes/no) disease, varying modeling practices for parity or breast-feeding history that may reduce internal doses of lipophilic POPs (LaKind et al. 2009), and reliance on serum or plasma in lieu of quantification in fat, the presumed gold standard for lipophilic chemicals (Johnson-Restrepo et al. 2005; Whitcomb et al. 2005). We designed the Endometriosis: Natural History, Diagnosis and Outcomes (ENDO) Study to further delineate the relation between lipophilic POPs and endometriosis.
