Lifestyle and Environment · Environmental Exposures
Smarr MM, Kannan K, Buck Louis GM
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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.
Marroquin JM et al., 2025 · Environ Health Perspect · Free full text on PubMed Central
Perand polyfluoroalkyl substances (PFAS) exposure is widespread and has been linked with gynecologic disease. To our knowledge, no study has measured PFAS in endometrial tissue. Eutopic endometrial tissue specimens (n=434) were collected from Investigating Mixtures of Pollutants and Endometriosis in Tissue (IMPLANT) study participants undergoing laparoscopy or laparotomy for any indication (2007-2009). Nine PFAS were measured by high-performance liquid chromatography-tandem mass spectrometry [perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorododecanoic acid (PFDoDA), perfluoroheptanoic acid (PFHpA), perfluorooctanesulfonamide (PFOSA), and perfluoroundecanoic acid (PFUnDA)]. Surgeons diagnosed endometriosis by gold-standard visualization and evaluated the endometriosis staging as moderate and severe (stages 3 and 4) compared to minimal and mild (stages 1 and 2) using American Society of Reproductive Medicine (ASRM) classification. We used modified Poisson regression models adjusted for age (continuous), race (white, all other race/ethnicities), smoking status (serum cotinine >10 ng/mL), study site (Utah, California), and body mass index (continuous) to obtain relative risks (RR) of endometriosis diagnosis and 95% confidence intervals (CIs) for each PFAS. PFAS mixtures were evaluated using Bayesian kernel machine regression. Participants were, on average, 33±7 years old, and 75% of participants were non-Hispanic white. Of the 181 participants with an incident endometriosis diagnosis, 73% had ASRM stage 1 or 2, while 27% had stage 3 or 4. Median [interquartile range (IQR)] eutopic endometrium tissue levels, in nanograms per gram, were 6.58 (6.44) for PFOS, 1.93 (1.71) for PFOA, 0.65 (0.75) for PFHxS, 0.58 (0.52) for PFNA, and 0.12 (0.18) for PFOSA. PFAS in the endometrial tissue was not associated with endometriosis. However, select PFAS in the eutopic tissue were associated with a risk of more advanced (stage 3 or 4 vs. 1 or 2) endometriosis [PFOSA RR=1.25 (95% CI: 1.10, 1.43), PFHxS RR=1.37 (95% CI: 1.12, 1.68), PFOS RR=1.36 (95% CI: 1.02, 1.81)]. PFAS were widely detected in eutopic endometrial tissue. There was no evidence that PFAS in endometrial tissue were associated with a higher risk of endometriosis diagnosis. However, PFOS, PFOSA, and PFHxS in the endometrial tissue were associated with risk of more severe stage of endometriosis. https://doi.org/10.1289/EHP15852.
Zhu H et al., 2020 · Environmental Pollution
Per- and polyfluoroalkyl substances (PFASs) are used in specialty/functional textiles to impart oil, water, and stain repellency. Little is known, however, with regard to the occurrence of PFASs in textiles including infant clothing. In this study, 13 perfluoroalkyl acids (PFAAs), comprising four perfluoroalkyl sulfonic acids (PFSAs; C4-C10) and nine perfluoroalkyl carboxylic acids (PFCAs; C4-C12) were determined in 160 textile samples collected from the United States. Two extraction methods, one involving a simple solvent extraction (i.e., before oxidation) and the other with an oxidative treatment (i.e., after oxidation) of textile extracts, were used. The sum concentrations of 13 PFAAs (i.e., ∑PFAA) in textile extracts before oxidation ranged from 2 (2 (14.2 ng/g). ∑PFAA concentrations were the highest in flame retarded textiles (n = 23; mean: 13.3 μg/m2; 59.4 ng/g), followed by water repellent textiles (n = 56; 2.88 μg/m2; 12.9 ng/g) and infant clothes (n = 81; 0.521 μg/m2; 2.33 ng/g). C4-C10 PFCAs accounted for at least three-quarters of the ∑PFAA content in our textile samples. Textile extracts analyzed after oxidative treatment exhibited ∑PFAA concentrations 10-fold higher than those in extracts analyzed prior to oxidation, which suggested that PFAA precursors are used in textiles. Precursors that generated C4-C5 PFCAs, upon oxidation, were more prevalent than those that yielded PFOA. The calculated dermal exposure doses in infants of PFAAs present in clothes were at least 1-2 orders of magnitude below the reference doses proposed by the United States Environmental Protection Agency. This is the first time that the oxidative treatment was applied in the analysis of PFASs in textiles, and our results suggest the existence of PFCA precursors in textiles.
Gaylord A et al., 2020 · Environ Res
Celiac disease affects approximately 1% of the population worldwide. Little is known about environmental factors that may modulate risk in genetically susceptible populations. Persistent organic pollutants (POPs) are known endocrine disruptors and, given the interplay between the endocrine and immune systems, are plausible contributors to celiac disease. The current study aims to elucidate the association between POPs and celiac disease. We conducted a single-site pilot study of 88 patients recruited from NYU Langone's Hassenfeld Children's Hospital outpatient clinic, 30 of which were subsequently diagnosed with celiac disease using standard serology and duodenal biopsy examination. Polybrominated diphenyl ether (PBDEs), perfluoroalkyl substances (PFASs), and p,p'-dichlorodiphenyldichloroethylene (DDE) and HLA-DQ genotype category were measured in blood serum and whole blood, respectively. Multivariable logistic regressions were used to obtain odds ratios for celiac disease associated with serum POP concentrations. Controlling for sex, race, age, BMI, and genetic susceptibility score, patients with higher serum DDE concentrations had 2-fold higher odds of celiac disease (95% CI: 1.08, 3.84). After stratifying by sex, we found higher odds of celiac disease in females with serum concentrations of DDE (OR = 13.0, 95% CI = 1.54, 110), PFOS (OR = 12.8, 95% CI = 1.17, 141), perfluorooctanoic acid (OR = 20.6, 95% CI = 1.13, 375) and in males with serum BDE153, a PBDE congener (OR = 2.28, 95% CI = 1.01, 5.18). This is the first study to report on celiac disease with POP exposure in children. These findings raise further questions of how environmental chemicals may affect autoimmunity in genetically susceptible individuals.
Buck Louis GM et al., 2016 · J Womens Health (Larchmt) · Free full text on PubMed Central
Endometriosis is a gynecologic disease reported to be associated with infertility and, possibly, adverse pregnancy outcomes. While considerable research focuses on pregnancy outcomes following diagnosis and/or treatment, few data actually describe women's reproductive history before diagnosis for a more complete understanding of endometriosis and reproduction. The study sample comprised 473 women (aged 18-44 years) undergoing laparoscopies or laparotomies, irrespective of surgical indication at 14 clinical sites, during the period 2007-2009. Upon enrollment and before surgery, women were queried about pregnancy intentions and the time required to become pregnant for planned pregnancies. Endometriosis was defined as surgically visualized disease. Using discrete time survival analysis, we estimated fecundability odds ratios (FORs) and 95% confidence intervals (CIs) to assess time to pregnancy (TTP) after adjusting for potential confounders (age, body composition, cigarette smoking, site). Generalized estimating equations accounted for multiple pregnancy attempts per woman. FORs ResultsApproximately 66% and 69% of women with and without endometriosis, respectively, reported having a planned pregnancy before surgery, respectively. After adjustment, an endometriosis diagnosis was associated with ≈29% reduction in fecundity or a longer TTP across all pregnancy-trying attempts (adjusted FOR = 0.71; 95% CI 0.46-1.10). While FORs were consistently ConclusionsWomen with endometriosis had a longer TTP than unaffected women, irrespective of disease severity, although the findings did not achieve significance. Prior reproductive history may be informative for predicting fecundity and pregnancy outcomes following diagnosis/treatment.
Buck Louis GM et al., 2012 · Environ Health Perspect · Free full text on PubMed Central
An equivocal literature exists regarding the relation between persistent organochlorine pollutants (POPs) and endometriosis in women, with differences attributed to methodologies. We assessed the association between POPs and the odds of an endometriosis diagnosis and the consistency of findings by biological medium and study cohort. 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. 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). 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.
Louis GMB et al., 2011 · ISEE Conference Abstracts
Background and Persistent organic pollutants (POPs) have been associated with endometriosis, though with equivocal results possibly reflecting choice of biospecimen. We sought to assess this ...
Buck Louis GM et al., 2013 · Fertil Steril · Free full text on PubMed Central
To assess in utero exposures and the odds of an endometriosis diagnosis. Matched cohort design. Fourteen participating clinical centers in geographically defined areas in Utah and California. PATIENT(S): Operative cohort comprised 473 women undergoing laparoscopy/laparotomy, and an ageand residence-matched population cohort comprising 127 women undergoing pelvic magnetic resonance imaging (MRI), 2007-2009. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Women completed standardized interviews before surgery or MRI regarding in utero exposures: mothers' lifestyle during the index pregnancy, and the index woman's gestation and birth size. Endometriosis was defined as visually confirmed disease in the operative cohort, and MRI visualized disease in the population cohort. The odds of an endometriosis diagnosis and corresponding 95% confidence intervals (CI) were estimated for each exposure by cohort using logistic regression and adjusting for current smoking, age at menarche, body mass index, and study site. RESULT(S): Endometriosis was diagnosed in 41% and 11% of women in the operative and population cohorts, respectively. In the primary analysis, adjust odds ratios (AORs) were elevated for maternal vitamin usage (1.27; 95% CI, 0.85-1.91), maternal cigarette smoking (1.16; 95% CI = 0.61-2.24), and low birth weight (1.1; 95% CI, 0.92-1.32). Reduced odds were observed for maternal usage of caffeine (0.99; 95% CI, 0.64-1.54), alcohol (0.82; 95% CI, 0.35-1.94), paternal cigarette smoking (0.72; 95% CI, 0.43-1.19), and preterm delivery (0.98; 95% CI, 0.47-2.03). Sensitivity analyses mostly upheld the primary results except for a decreased AOR for preterm birth (0.41; 95% CI, 0.18-0.94) when restricting to visualized and histologically confirmed endometriosis in the operative cohort. CONCLUSION(S): In utero exposures were not statistically significantly associated with the odds of an endometriosis diagnosis in either cohort.
Pollack AZ et al., 2013 · Reprod Toxicol · Free full text on PubMed Central
There has been limited study of trace elements and endometriosis. Using a matched cohort design, 473 women aged 18-44 years were recruited into an operative cohort, along with 131 similarly aged women recruited into a population cohort. Endometriosis was defined as surgically visualized disease in the operative cohort, and magnetic resonance imaging diagnosed disease in the population cohort. Twenty trace elements in urine and three in blood were quantified using inductively coupled plasma mass spectrometry. Logistic regression estimated the adjusted odds (aOR) of endometriosis diagnosis for each element by cohort. No association was observed between any element and endometriosis in the population cohort. In the operative cohort, blood cadmium was associated with a reduced odds of diagnosis (aOR=0.55; 95% CI: 0.31, 0.98), while urinary chromium and copper reflected an increased odds (aOR=1.97; 95% CI: 1.21, 3.19; aOR=2.66; 95% CI: 1.26, 5.64, respectively). The varied associations underscore the need for continued research.