Phthalates and risk of endometriosis.
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ABSTRACT:
SUBMITTER: Upson K
PROVIDER: S-EPMC3905445 | biostudies-literature | 2013 Oct
REPOSITORIES: biostudies-literature
Publications
Phthalates and risk of endometriosis.
Upson Kristen K Sathyanarayana Sheela S De Roos Anneclaire J AJ Thompson Mary Lou ML Scholes Delia D Dills Russell R Holt Victoria L VL
Environmental research 20130725
<h4>Background</h4>Phthalates are ubiquitous environmental chemicals with endocrine disruptive properties. The impact of these chemicals on endocrine-related disease in reproductive-age women is not well understood.<h4>Objective</h4>To investigate the relationship between urinary phthalate metabolite concentrations and the risk of a hormonally-driven disease, endometriosis, in reproductive-age women.<h4>Methods</h4>We used data from a population-based case-control study of endometriosis, conduct ...[more]
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Project description:Environmental factors that have been linked to an increased endometriosis risk include exposure to di-(2-ethylhexyl)-phthalate (DEHP), an endocrine disruptor. This study aims to investigate whether DEHP in vitro exposure in primary endometrial stromal cells (EnSC), primary endometrial epithelial cells (EnEC), and the human endometrial adenocarcinoma cell line Ishikawa properly mimics alterations described in the eutopic endometrium of women with endometriosis. Primary EnSC and EnEC, isolated from six fertile egg donors, and Ishikawa cells were exposed to DEHP (0.1, 1, and 10 µM) and were assessed for viability, endometriosis markers (IL-6, VEGF-A, HOXA10, EZH2, and LSD1), steroid receptor gene expressions (ER-1, ER-2, PR-T, PR-B, and PGRMC1), and invasive capacity. Viability after 72 h of DEHP exposure was not significantly affected. None of the endometriosis markers studied were altered after acute DEHP exposure, nor was the expression of steroid receptors. The invasive capacity of EnSC was significantly increased after 10 µM of DEHP exposure. In conclusion, acute DEHP exposure in primary endometrial cells does not fully phenocopy the changes in the viability, expression of markers, or steroidal receptors described in endometriosis. However, the significant increase in EnSC invasiveness observed after DEHP exposure could be a link between DEHP exposure and increased endometriosis likelihood.
| S-EPMC9569573 | biostudies-literature
Project description:Endometriosis is a major health care challenge because many young women with endometriosis go undetected for an extended period, which may lead to pain sensitization. Clinical tools to better identify candidates for laparoscopy-guided diagnosis are urgently needed. Since endometriosis has a strong genetic component, there is a growing interest in using genetics as part of the clinical risk assessment. The aim of this work was to investigate the discriminative ability of a polygenic risk score (PRS) for endometriosis using three different cohorts: surgically confirmed cases from the Western Danish endometriosis referral Center (249 cases, 348 controls), cases identified from the Danish Twin Registry (DTR) based on ICD-10 codes from the National Patient Registry (140 cases, 316 controls), and replication analysis in the UK Biobank (2,967 cases, 256,222 controls). Patients with adenomyosis from the DTR (25 cases) and from the UK Biobank (1,883 cases) were included for comparison. The PRS was derived from 14 genetic variants identified in a published genome-wide association study with more than 17,000 cases. The PRS was associated with endometriosis in surgically confirmed cases [odds ratio (OR) = 1.59, p = 2.57× 10-7] and in cases from the DTR biobank (OR = 1.50, p = 0.0001). Combining the two Danish cohorts, each standard deviation increase in PRS was associated with endometriosis (OR = 1.57, p = 2.5× 10-11), as well as the major subtypes of endometriosis; ovarian (OR = 1.72, p = 6.7× 10-5), infiltrating (OR = 1.66, p = 2.7× 10-9), and peritoneal (OR = 1.51, p = 2.6 × 10-3). These findings were replicated in the UK Biobank with a much larger sample size (OR = 1.28, p < 2.2× 10-16). The PRS was not associated with adenomyosis, suggesting that adenomyosis is not driven by the same genetic risk variants as endometriosis. Our results suggest that a PRS captures an increased risk of all types of endometriosis rather than an increased risk for endometriosis in specific locations. Although the discriminative accuracy is not yet sufficient as a stand-alone clinical utility, our data demonstrate that genetics risk variants in form of a simple PRS may add significant new discriminatory value. We suggest that an endometriosis PRS in combination with classical clinical risk factors and symptoms could be an important step in developing an urgently needed endometriosis risk stratification tool.
| S-EPMC9580817 | biostudies-literature
Project description:ObjectiveTo study early-life factors in relation to endometriosis risk in adulthood.DesignPopulation-based case-control study.SettingIntegrated healthcare system.Patient(s)Cases (n = 310) were women diagnosed for the first time with endometriosis between the years 1996 and 2001, and controls (n = 727) were women without a diagnosis of endometriosis randomly selected from the healthcare system population.Intervention(s)None.Main outcome measure(s)Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the associations between intrauterine diethylstilbestrol (DES) exposure, maternal smoking, mother's age at delivery, firstborn status, birth weight, fetal number, prematurity, and regular soy formula feeding during infancy and endometriosis were estimated using unconditional logistic regression, adjusting for frequency matching and confounding variables. Information on early-life factors was ascertained retrospectively by in-person interview, with information on maternal DES use and regular soy formula feeding directly gathered from the participant's mother or other family member.Result(s)We observed that women who were regularly fed soy formula as infants had more than twice the risk of endometriosis compared with unexposed women (aOR 2.4, 95% CI 1.2-4.9). Our data also suggested increased endometriosis risk with prematurity (aOR 1.7, 95% CI 0.9-3.1) and maternal use of DES (OR 2.0, 95% CI 0.8-4.9, adjusting only for frequency matching variables), although these confidence intervals included the null.Conclusion(s)Our results support the hypothesis that disruption of development during fetal and infant periods may increase the risk of endometriosis in adulthood.
| S-EPMC5328429 | biostudies-literature
Project description:Wide utilization of phthalates-containing products results in the significant exposure of humans to these compounds. Many adverse effects of phthalates have been documented in rodent models, but their effects in humans exposed to these chemicals remain unclear until more mechanistic studies on phthalate toxicities can be carried out. To provide new insights to predict the potential adverse effects of phthalates in humans, the recent study investigated the inhibition of representative phthalates di-n-octyl ortho-phthalate (DNOP) and diphenyl phthalate (DPhP) towards the important xenobiotic and endobiotic-metabolizing UDP-glucuronosyltransferases (UGTs). An in vitro UGTs incubation system was employed to study the inhibition of DNOP and DPhP towards UGT isoforms. DPhP and DNOP weakly inhibited the activities of UGT1A1, UGT1A7, and UGT1A8. 100 µM of DNOP inhibited the activities of UGT1A3, UGT1A9, and UGT2B7 by 41.8% (p < 0.01), 45.6% (p < 0.01), and 48.8% (p < 0.01), respectively. 100 µM of DPhP inhibited the activity of UGT1A3, UGT1A6, and UGT1A9 by 81.8 (p < 0.001), 49.1% (p < 0.05), and 76.4% (p < 0.001), respectively. In silico analysis was used to explain the stronger inhibition of DPhP than DNOP towards UGT1A3 activity. Kinetics studies were carried our to determine mechanism of inhibition of UGT1A3 by DPhP. Both Dixon and Lineweaver-Burk plots showed the competitive inhibition of DPhP towards UGT1A3. The inhibition kinetic parameter (Ki) was calculated to be 0.89 µM. Based on the [I]/Ki standard ([I]/Ki < 0.1, low possibility; 1>[I]/Ki > 0.1, medium possibility; [I]/Ki > 1, high possibility), these studies predicted in vivo drug-drug interaction might occur when the plasma concentration of DPhP was above 0.089 µM. Taken together, this study reveales the potential for adverse effects of phthalates DNOP and DPhP as a result of UGT inhibition.
| S-EPMC6300982 | biostudies-literature
Project description:Objective: The etiology of endometriosis is still a research field in which few consistent data are available. Large case-control studies or even cohort studies are rare, and most of the published data are conflicting. The aim of the present study was therefore to examine common epidemiological and endometriosis-specific risk factors in a German case-control study. Design: From 2001 to 2010, a pool of 595 laparoscopically confirmed cases and 475 controls were recruited in a hospital-based setting. After matching for age, 298 cases and 300 controls remained in the pool. Age at menarche, menstrual cycle length, duration of menstrual bleeding, number of pregnancies, live births, miscarriages, use of contraceptive pills, body mass index (BMI), and smoking status were analyzed with logistic regression models predicting endometriosis case-control status. Results: Menstrual cycle length, duration of menstrual bleeding, number of pregnancies, number of miscarriages, and smoking status, as relevant predictors for endometriosis case-control status, were identified as risk factors for endometriosis. Other factors such as age at menarche, number of live births, ever having used contraceptive pills, and BMI were not predictive. Conclusions: This hospital-based case-control study reproduced most of the familiar risk factors. Comparison of this study with others reveals a wide variety of effect sizes and directions of association with risk factors and may increase the information available about the characteristics of the patient population being treated in the relevant hospital setting.
| S-EPMC4166917 | biostudies-other
Project description:BackgroundModifiable risk factors such as diet may be important in both the etiology and progression of endometriosis as well as the prevalence of pain symptoms and infertility associated with this condition. In adults, higher intake of dairy has been associated with a lower risk of endometriosis diagnosis. There is currently no literature on whether dairy intake during adolescence, a potentially critical window of exposure, influences endometriosis risk.ObjectiveThe objectige of the study was to evaluate the association between consumption of dairy foods in adolescence and the risk of laparoscopically confirmed endometriosis.Study designThis was a prospective cohort study, the Nurses' Health Study II, which has prospectively collected data since 1989. In 1998, when participants were aged 34-51 years, they completed a 124 item food frequency questionnaire about their high school diet. Cases were defined as those who self-reported laparoscopically confirmed endometriosis. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals for the association between dairy foods and laparoscopically confirmed endometriosis.ResultsAmong women who completed the questionnaire about their high school diet in 1998, 581 cases of laparoscopically confirmed endometriosis were diagnosed among 32,868 premenopausal women from 1998 to 2013. Women who consumed more than 4 servings per day of dairy foods during adolescence had a 32% lower risk of laparoscopically confirmed endometriosis during adulthood (95% confidence interval, 0.47-0.96; Ptrend = .04) compared with women consuming 1 or fewer servings per day. The association was similar for low-fat and high-fat dairy foods. Yogurt and ice cream consumption, specifically, were associated with a lower risk of endometriosis. Those who consumed 2 or more servings of yogurt per week as an adolescent had a 29% lower risk of endometriosis diagnosis (95% confidence interval, 0.52-0.97; Ptrend = .02) compared with those consuming less than 1 serving per week. In addition, women who consumed 1 or more servings per day of ice cream per day during adolescence had a 38% lower risk of endometriosis diagnosis (95% confidence interval, 0.40-0.94; Ptrend = .20) compared with those consuming less than 1 serving per week.ConclusionOur findings suggest that dairy consumption, specifically yogurt and ice cream intake, in adolescence may reduce the risk of subsequent endometriosis diagnosis. Future studies in adolescent populations are needed to confirm these results.
| S-EPMC7056553 | biostudies-literature
Project description:Study questionIs there an association between physical and sexual abuse occurring in childhood or adolescence and risk of laparoscopically-confirmed endometriosis?Summary answerEarly life sexual and physical abuse was associated with an increased risk of endometriosis.What is known alreadyPrevious studies have reported that physical and sexual abuse are associated with chronic pelvic pain (CPP). However, only one study has examined the association between childhood physical abuse and laparoscopically-confirmed endometriosis, and did not observe an association with endometriosis risk.Study design, size, durationProspective cohort study using data collected from 60 595 premenopausal women from 1989 to 2013 as part of the Nurses' Health Study II cohort.Participants/materials, setting, methodsParticipants completed an exposure to violence victimization questionnaire in 2001. Cases were restricted to laparoscopically-confirmed endometriosis. Cox proportional hazards models were used to calculate rate ratios (RR) and 95% confidence intervals (CI).Main results and the role of chanceThree thousand three hundred and ninety-four cases of laparoscopically-confirmed endometriosis were diagnosed during 24 years of follow-up. Compared to those reporting no physical or sexual abuse, the risk of endometriosis was greater among those who experienced severe physical abuse (RR = 1.20; 95% CI = 1.06, 1.37) or severe sexual abuse (RR = 1.49; 95% CI = 1.24, 1.79). There was a 79% increased risk of laparoscopically-confirmed endometriosis for women reporting severe-chronic abuse of multiple types (95% CI = 1.44, 2.22). The associations between abuse and endometriosis were stronger among women presenting without infertility, a group that was more likely to have been symptomatic with respect to pain.Limitations, reasons for cautionThe violence exposure was recalled by the study participants and thus is subject to misclassification as well as recall bias for the cases who were diagnosed prior to 2001. However, our results were similar in a sensitivity analysis including only endometriosis cases incident after their violence history report. In addition, residual or unmeasured confounding is a possibility; however, we were able to adjust for a variety of potential early life confounders. Finally, selection bias is also a possibility if those who chose to return the violence questionnaire did so based jointly on abuse history and endometriosis risk.Wider implications of the findingsEarly life sexual and physical abuse was associated with an increased risk of endometriosis. Severity, chronicity and accumulation of types of abuse were associated with greater risk. Understanding the mechanisms underlying these relations may better define the biologic impacts of abuse and the related pathophysiology of endometriosis.Study funding/competing interest(s)This work was supported by National Institute of Child Health and Human Development [Grant numbers HD48544, HD52473, HD57210 and CA50385] and the Atlanta Clinical and Translational Science Institute [Grant number ULRR025008]. The Nurses' Health Study II is supported by the National Institutes of Health grant UM1 CA176726 from the National Cancer Institute. H.R.H. is supported by the National Cancer Institute, National Institutes of Health [Grant number K22 CA193860]. Authors report no conflict of interest.
| S-EPMC6112577 | biostudies-literature
Project description:PurposeEstrogen metabolizing gene mutations can be associated with defective hormonal signaling leading to disease processes. Endometriosis is an estrogen dependent that can be influenced by defective signaling in the estrogen pathway.ObjectivesTo evaluate the association of A/G 85952 CYP2C19 and A/G 937 HSD17B1 gene polymorphisms with endometriosis through the investigation of a large Brazilian sample of women with endometriosis and a fertile control group.MethodsFive hundred women with endometriosis and 500 women without endometriosis were tested for CYP2C19 and HSD17B1 polymorphisms, by TaqMan Real Time PCR. The results were statistically analyzed by chi-square, logistic regression and tested for Hardy-Weinberg equilibrium.ResultsThe comparison of genotype and allelic frequency of CYP2C19 polymorphism (rs11592737) in patients with endometriosis and control group showed a statistically significant difference (p = 0.0203) and for the HSD17B1 polymorphism (rs605059) differences were not significant (p = 0.0687). Comparing the stages I/II and III/IV endometriosis with the control group for the CYP2C19 we observed p = 0.0133 and p = 0.0564, respectively, and for HSD17B1 the values for p = 0.4319 and p = 0.0667.ConclusionWe observed that CYP2C19 polymorphism is associated with endometrisis in Brazilian women and can be considered a potential biomarker of the disease.
| S-EPMC4294871 | biostudies-literature
Project description:Study questionIs there a relationship between severe teenage acne and endometriosis?Summary answerEndometriosis is positively associated with severe teenage acne.What is known alreadyNo studies have specifically explored a possible association between severe acne in adolescence and risk of endometriosis.Study design, size, durationThis prospective cohort study used data collected from 88 623 female nurses from September 1989 to June 2009 as part of the Nurses' Health Study II (NHS II) cohort.Participants/materials, setting, methodsRegression models were used to calculate hazard ratios (HRs) and confidence intervals (CIs) for endometriosis among women with and without severe teenage acne. Multivariate models were adjusted for established risk factors of endometriosis.Main results and the role of chanceA total of 4 382 laparoscopically confirmed endometriosis cases were documented during 1 132 272 woman-years of follow-up. Compared with women without a history of severe teenage acne, women who had severe teenage acne had a 20% increased risk of endometriosis (HR = 1.20, 95% CI: 1.08-1.32). The association was not affected by adjusting for use of tetracycline or isotretinoin.Limitations and reasons for cautionThe HR is likely to be underestimated since we only included endometriosis cases confirmed by laparoscopy. Although geographically diverse, the NHS II cohort is primarily Caucasian, which may limit generalization to more ethnically diverse populations.Wider implications of the studyThe results of this study suggest that severe teenage acne is associated with an increased risk of endometriosis. As a visible and non-invasive clinical indicator, severe teenage acne may be useful for early detection of endometriosis. We bring this counter-intuitive association to the attention of clinicians for the benefit of the patient and an early diagnosis of endometriosis.Study funding/competing interestThis study was funded by research grant CA176726 from the National Institute of Health. M.K. is supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme (#PIOF-GA-2011-302078). The funding agencies had no role in the design of the study, in the analysis and interpretation of the data, in the writing of the report or in the decision to submit the paper for publication.
| S-EPMC4191450 | biostudies-literature
Project description:ObjectiveTo investigate the relationship between endometriosis and adverse pregnancy outcomes.MethodsWomen between ages 25 and 42 years in 1989 (n=116,429) reported detailed information on pregnancies and reproductive health at baseline and every 2 years thereafter in the Nurses' Health Study II, a cohort study. In 2009, they completed a detailed, pregnancy-focused questionnaire. A total of 196,722 pregnancies were reported. Adverse pregnancy outcomes included spontaneous abortion, ectopic pregnancy, stillbirth, gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (preeclampsia or gestational hypertension), preterm birth, and low birth weight. We estimated the relative risks (RRs) and 95% CIs of adverse pregnancy outcomes comparing pregnancies in women with and without a history of laparoscopically confirmed endometriosis using multivariable log-binomial regression, with generalized estimating equations to account for multiple pregnancies per woman.ResultsEndometriosis was associated with a greater risk of pregnancy loss (spontaneous abortion: RR 1.40, 95% CI 1.31-1.49; ectopic pregnancy: RR 1.46, 95% CI 1.19-1.80). Endometriosis was also associated with a greater risk of GDM (RR 1.35, 95% CI 1.11-1.63) and hypertensive disorders of pregnancy (RR 1.30, 95% CI 1.16-1.45).ConclusionsWe observed an association between laparoscopically confirmed endometriosis and several adverse pregnancy outcomes. Future research should focus on the potential biological pathways underlying these relationships to inform screening or preventive interventions.
| S-EPMC6922084 | biostudies-literature