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      Endometriosis and Organochlorinated Environmental Pollutants: A Case–Control Study on Italian Women of Reproductive Age

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          Abstract

          Background

          Endometriosis is a common gynecologic disease characterized by the ectopic growth of endometrial tissue. In industrialized countries, it affects approximately 10% of women of reproductive age. Its etiology is unclear, but a multifactorial origin is considered to be most plausible. Environmental organochlorinated persistent pollutants, in particular dioxins and polychlorinated biphenyls (PCBs), have been hypothesized to play a role in the disease etiopathogenesis. However, results of studies carried out on humans are conflicting.

          Objective

          We evaluated the exposure to organochlorinated persistent pollutants as a risk factor for endometriosis.

          Methods

          We conducted a case–control study in Rome on 158 women comprising 80 cases and 78 controls. In all women, serum concentrations of selected non-dioxin-like PCBs (NDL-PCBs) and dioxin-like PCBs (DL-PCBs), 1,1-dichloro-2,2,- bis(4-chlorophenyl)-ethene ( p,p′-DDE), and hexachlorobenzene (HCB) were determined by ion-trap mass spectrometry. DR-CALUX bioassay was employed to assess the 2,3,7,8-tetrachlorodibenzo- p-dioxin toxicity equivalent (TEQ) concentrations of polychlorinated dibenzo- p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and DL-PCBs.

          Results

          We found an increased risk of endometriosis for DL-PCB-118 [odds ratio (OR) = 3.79; 95% confidence interval (CI), 1.61–8.91], NDL-PCB-138 (OR = 3.78; 95% CI, 1.60–8.94), NDL-PCB-153 (OR = 4.88; 95% CI, 2.01–11.0), NDL-PCB-170 (OR = 3.52; 95% CI, 1.41–8.79), and the sum of DL-PCBs and NDL-PCBs (OR = 5.63; 95% CI, 2.25–14.10). No significant associations were observed with respect to HCB or to the sum of PCDDs, PCDFs, and DL-PCBs given as total TEQs.

          Conclusions

          The results of this study show that an association exists between increased PCB and p,p′-DDE serum concentrations and the risk of endometriosis.

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          Most cited references37

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          Age at menarche and tanner stage in girls exposed in utero and postnatally to polybrominated biphenyl.

          Accidental contamination of the Michigan food chain with polybrominated biphenyls (PBBs) led to the exposure of more than 4,000 individuals in 1973. Because PBB exposure is suspected to disrupt endocrine function, we assessed pubertal development in females 5-24 years of age (N = 327) who were exposed to PBB in utero and, in many cases, through breastfeeding. We estimated in utero PBB exposure using maternal serum PBB measurements taken after exposure (1976-1979) and extrapolated to time of pregnancy using a model of PBB decay. We found that breastfed girls exposed to high levels of PBB in utero (> or =7 parts per billion) had an earlier age at menarche (mean age = 11.6 years) than breastfed girls exposed to lower levels of PBB in utero (mean age = 12.2-12.6 years) or girls who were not breastfed (mean age = 12.7 years). This association persisted after adjustment for potential confounders (menarche ratio = 3.4, 95% confidence interval = 1.3-9.0). Perinatal PBB exposure was associated with earlier pubic hair stage in breastfed girls, but little association was found with breast development. The associations observed here lend support to the hypothesis that pubertal events may be affected by pre- and postnatal exposure to organohalogens.
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            Endometriosis in rhesus monkeys (Macaca mulatta) following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

            The incidence of the reproductive disease endometriosis was determined in a colony of rhesus monkeys chronically exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) for a period of 4 years. Ten years after termination of dioxin treatment, the presence of endometriosis was documented by surgical laparoscopy and the severity of disease was assessed. The incidence of endometriosis was directly correlated with dioxin exposure and the severity of disease was dependent upon the dose administered (p < 0.001). Three of 7 animals exposed to 5 ppt dioxin (43%) and 5 of 7 animals exposed to 25 ppt dioxin (71%) had moderate to severe endometriosis. In contrast, the frequency of disease in the control group was 33%, similar to an overall prevalence of 30% in 304 rhesus monkeys housed at The Harlow Primate Center with no dioxin exposure. This 15-year study indicates that latent female reproductive abnormalities may be associated with dioxin exposure in the rhesus. Therefore, the effects of this toxin may be more diverse than previously recognized.
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              Dioxin/polychlorinated biphenyl body burden, diabetes and endometriosis: findings in a population-based study in Belgium.

              Dioxins and polychlorinated biphenyls (PCBs) are persistent organic pollutants widely distributed in the food chain, which is the main source of human exposure. Their effects on human health at background exposure levels are still poorly understood. Recent epidemiological evidence suggests a possible association between these pollutants and diabetes. We report here the results of a population-based study in Belgium on 257 (142 women and 115 men) environmentally exposed subjects, including 10 cases of endometriosis and nine cases of diabetes. Seventeen 2,3,7,8-polychlorinated dibenzodioxins/dibenzofurans (PCDD/Fs or dioxins), four coplanar PCBs (International Union of Pure and Applied Chemistry [IUPAC] nos 77, 81, 126 and 169) and 12 PCB markers (IUPAC nos 3, 8, 28, 52, 101, 118, 138, 153, 180, 194, 206 and 209) were quantified in serum fat from fasting blood samples in order to estimate the body burden of these pollutants. Whilst no difference was found between women with endometriosis and their controls, diabetic patients had significantly increased serum levels of dioxins, coplanar PCBs and the 12 PCB markers. After adjustment for age and other covariates, serum total toxic equivalent activity (sum of PCDD/Fs and coplanar PCBs) and 12 PCB marker concentrations in diabetics were 62% (p = 0.0005) and 39% (p = 0.0067) higher, respectively, than in controls. The risk of diabetes was significantly increased in subjects in the top decile for adjusted concentrations of dioxins (odds ratio 5.1, 95% confidence interval [CI] 1.18-21.7), coplanar PCBs (odds ratio 13.3, 95% CI 3.31-53.2) or 12 PCB markers (odds ratio 7.6, 95% CI 1.58-36.3). These findings warrant further studies to assess the significance of the associations between diabetes and environmental exposure to polychlorinated pollutants.
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                Author and article information

                Journal
                Environ Health Perspect
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                1552-9924
                July 2009
                31 March 2009
                : 117
                : 7
                : 1070-1075
                Affiliations
                [1 ] Department of Gynaecology and Obstetrics, Sapienza University of Rome, Rome, Italy
                [2 ] National Centre for Epidemiology, Surveillance and Health Promotion, National Institute for Health, Rome, Italy
                [3 ] Department of the Environment and Primary Prevention, National Institute for Health, Rome, Italy
                [4 ] Service for Biotechnology and Animal Welfare, National Institute for Health, Rome, Italy
                Author notes
                Address correspondence to E. De Felip, Unit of Toxicological Chemistry, Department of the Environment and Primary Prevention, National Institute for Health, Viale Regina Elena, 299 00161 Rome, Italy. Telephone: 39 06 4990 2904. Fax: 39 06 4990 2836. E-mail: defelip@ 123456iss.it
                [*]

                These authors contributed equally to this work.

                The authors declare they have no competing financial interests.

                Article
                ehp-117-1070
                10.1289/ehp.0800273
                2717132
                19654915
                cf38928f-dbd5-4b67-848a-635edb9391fe
                This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.
                History
                : 10 October 2008
                : 31 March 2009
                Categories
                Research

                Public health
                case-control study,pcbs,dioxins,endometriosis,biomonitoring
                Public health
                case-control study, pcbs, dioxins, endometriosis, biomonitoring

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