Combined Exposure to Multiple Endocrine Disruptors and Uterine Leiomyomata and Endometriosis in US Women

BackgroundUterine leiomyomata (UL) and endometriosis (EM) are common gynecological diseases damaging the reproductive health of fertile women. Among all the potential factors, environmental endocrine-disrupting chemicals are insufficiently addressed considering the multiple pollutants and mixture exposure.MethodsWomen aged 20 to 54 years old in the National Health and Nutrition Examination Survey (NHANES) 2001-2006, having a complete measurement of ten commonly exposed endocrine-disrupting chemicals (including urinary phthalate metabolites, equol, and whole blood heavy metals) and answered questions about UL and EM were included (N=1204). Multivariable logistic regression model, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models were implemented to analyze the combined effect of chemicals on the overall association with UL and EM.ResultsIn single chemical analysis, equol (OR: 1.90, 95% CI: 1.11, 3.27) and mercury (Hg) (OR: 1.91, 95% CI: 1.14, 3.25) were found positively associated with UL in tertile 3 vs. tertile 1. In WQS regression and BKMR models, the significant positive association between WQS index and UL (OR: 2.54, 95% CI: 1.52, 4.29) was identified and the positive relationship between equol and Hg exposure and UL were further verified. Besides, the mixture evaluation models (WQS and BKMR) also found MEHP negatively associated with UL. Although none of the single chemicals in tertile 3 were significantly associated with EM, the WQS index had a marginally positive association with EM (OR: 2.01, 95% CI: 0.98, 4.15), and a significant positive association was identified in subanalysis with participants restricted to premenopausal women (OR: 2.18, 95% CI: 1.03, 4.70). MIBP and MBzP weighted high in model of EM and MEHP weighted the lowest.ConclusionComparing results from these three statistical models, the associations between equol, Hg, and MEHP exposure with UL as well as the associations of MIBP, MBzP, and MEHP exposure with EM warrant further research.

Download Full-text

Environmental exposures to endocrine disrupting chemicals (EDCs) and their role in endometriosis: a systematic literature review

Reviews on Environmental Health ◽

10.1515/reveh-2020-0046 ◽

2020 ◽

Vol 0 (0) ◽

Cited By ~ 1

Author(s):

Diksha Sirohi ◽

Ruqaiya Al Ramadhani ◽

Luke D. Knibbs

Keyword(s):

Bisphenol A ◽

Phthalate Esters ◽

Endocrine Disrupting Chemicals ◽

Environmental Pollutants ◽

Positive Association ◽

Environmental Chemicals ◽

Reproductive Age ◽

Organochlorinated Pesticides ◽

Endocrine Disrupting ◽

The Relationship

AbstractPurposeEndocrine-related diseases and disorders are on the rise globally. Synthetically produced environmental chemicals (endocrine-disrupting chemicals (EDCs)) mimic hormones like oestrogen and alter signalling pathways. Endometriosis is an oestrogen-dependent condition, affecting 10–15% of women of the reproductive age, and has substantial impacts on the quality of life. The aetiology of endometriosis is believed to be multifactorial, ranging from genetic causes to immunologic dysfunction due to environmental exposure to EDCs. Hence, we undertook a systematic review and investigated the epidemiological evidence for an association between EDCs and the development of endometriosis. We also aimed to assess studies on the relationship between body concentration of EDCs and the severity of endometriosis.MethodFollowing PRISMA guidelines, a structured search of PubMed, Embase and Scopus was conducted (to July 2018). The included studies analysed the association between one or more EDCs and the prevalence of endometriosis. The types of EDCs, association and outcome, participant characteristics and confounding variables were extracted and analysed. Quality assessment was performed using standard criteria.ResultsIn total, 29 studies were included. Phthalate esters were positively associated with the prevalence of endometriosis. The majority (71%) of studies revealed a significant association between bisphenol A, organochlorinated environmental pollutants (dioxins, dioxin-like compounds, organochlorinated pesticides, polychlorinated biphenyls) and the prevalence of endometriosis. A positive association between copper, chromium and prevalence of endometriosis was demonstrated in one study only. Cadmium, lead and mercury were not associated with the prevalence of endometriosis. There were conflicting results for the association between nickel and endometriosis. The relationship of EDCs and severity of endometriosis was not established in the studies.ConclusionWe found some evidence to suggest an association between phthalate esters, bisphenol A, organochlorinated environmental pollutants and the prevalence of endometriosis. Disentangling these exposures from various other factors that affect endometriosis is complex, but an important topic for further research.

Download Full-text

Metabolic syndrome and endocrine disrupting chemicals: exposure and health effects

European Journal of Public Health ◽

10.1093/eurpub/ckaa166.086 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

E Haverinen ◽

R Lange ◽

H Tolonen

Keyword(s):

Metabolic Syndrome ◽

Bisphenol A ◽

Health Effects ◽

Endocrine Disrupting Chemicals ◽

Positive Association ◽

Human Biomonitoring ◽

European Population ◽

Priority Substances ◽

Metabolic Disturbances ◽

Endocrine Disrupting

Abstract Increasing prevalence of metabolic syndrome (MetS) is causing significant health burden among the European population. Current knowledge supports the notion that endocrine disrupting chemicals (EDCs) interfere with human metabolism and hormonal balance, contributing to the conventionally recognized life-style related risk factors for MetS. In relation to the Human biomonitoring initiative (HBM4EU) five priority substances (Bisphenol A, Per- and polyfluoroalkyl substances (PFASs), Phthalates, Cadmium and Arsenic) and their association with adverse metabolic health effects were examined. A methodological framework for scoping reviews was followed to increase consistency and transparency throughout the process. A literature review was conducted to identify epidemiological studies focusing on the association between MetS or its individual components and the five HBM4EU priority substances. Human biomonitoring studies have been able to present evidence supporting EDC exposure and development of individual MetS components; however the strength of the association varies between the components and EDCs. Most of the identified literature examined Bisphenol A and Phthalate exposure, usually targeting obesity, anthropometrics or glucose metabolism. Evidence suggests a positive association between Bisphenol A and Phthalate exposure and obesity-related components. The substance group of PFASs indicated weakest association, as the results were inconsistent and were suggestive only for a positive association with development of dyslipidaemia. Current evidence on metabolic disturbances and EDCs are inconclusive and fragmented, hence establishing harmonized and standardized human biomonitoring procedures among the European population are needed. Rigorous and ongoing human biomonitoring in combination with health monitoring could provide comprehensive information on EDC exposure and association of metabolic disturbances. Key messages EDC exposure is ubiquitous within European population, hence more human biomonitoring in combination with health surveys is needed to strengthen knowledge on human’s metabolic health. MetS is an increasing global health concern, which requires novel approaches to tackle the challenge.

Download Full-text

Endocrine-Disrupting Chemicals and Their Effects during Female Puberty: A Review of Current Evidence

International Journal of Molecular Sciences ◽

10.3390/ijms21062078 ◽

2020 ◽

Vol 21 (6) ◽

pp. 2078 ◽

Cited By ~ 4

Author(s):

Laura Lucaccioni ◽

Viola Trevisani ◽

Lucia Marrozzini ◽

Natascia Bertoncelli ◽

Barbara Predieri ◽

...

Keyword(s):

Endocrine Disrupting Chemicals ◽

Current Evidence ◽

Secondary Sexual Characteristics ◽

Endocrine Disrupting ◽

Sexual Characteristics ◽

Single Chemical ◽

Windows Of Susceptibility ◽

Physical Changes ◽

Temporal Windows

Puberty is the process of physical changes between childhood and adulthood during which adolescents reach sexual maturity and become capable of reproduction. It is considered one of the main temporal windows of susceptibility for the influence of the endocrine-disrupting chemicals (EDCs). EDCs may act as single chemical agents or as chemical mixtures; they can be pubertal influencers, accelerating and anticipating the processing of maturation of secondary sexual characteristics. Moreover, recent studies have started to point out how exposure to EDCs during puberty may predispose to breast cancer later in life. In fact, the estrogen-mimicking endocrine disruptors (EEDs) may influence breast tissue development during puberty in two main ways: the first is the action on the proliferation of the breast stromal cells, the second concerns epigenetic mechanisms. The aim of this mini-review was to better highlight what is new and what is not completely known regarding the role of EDCs during puberty.

Download Full-text

Adherence to the low carbohydrate diet and the risk of breast Cancer in Iran

Nutrition Journal ◽

10.1186/s12937-019-0511-x ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 1

Author(s):

Bahareh Sasanfar ◽

Fatemeh Toorang ◽

Ahmad Esmaillzadeh ◽

Kazem Zendehdel

Keyword(s):

Breast Cancer ◽

Postmenopausal Women ◽

Premenopausal Women ◽

Positive Association ◽

Carbohydrate Diet ◽

Significant Positive Association ◽

Low Carbohydrate Diet ◽

Low Carbohydrate ◽

Study Population ◽

Study Participants

Abstract Background Previous studies on the link between macronutrients and breast cancer have mostly focused on individual macronutrients rather than their combination. This study investigates the association between adherence to a low carbohydrate diet and odds of breast cancer among women. Methods This hospital-based case-control study was carried out on 412 women with pathologically confirmed breast cancer within the past year and 456 apparently healthy controls that were matched in terms of age and residential place. Dietary data was collected using a 168-item validated FFQ. Participants were classified in terms of quintiles of percentages of energy intake from carbohydrates, proteins, and fats. Then, individuals in the highest quintile of fat and protein intake were given a score of 5 and those in the lowest quintile of these macronutrients were given a score of 1. Participants in the other quintiles of these macronutrients were given the corresponding score. In terms of carbohydrate intake, those in the highest quintile received a score of 1 and those in the lowest quintile received 5. The scores were then summed up to calculate the total low carbohydrate diet (LCD) score, which varied from 3 to 15. A higher score meant greater adherence to a low carbohydrate diet. Results The mean age of study participants was 45.2 y and mean BMI was 28.4 kg/m2. Mean LCD score of participants was 8.9 ± 2.5 (8.9 ± 2.6 in cases and 9.0 ± 2.5 in controls). Although no significant association was observed between adherence to the LCD score and odds of breast cancer in the study population, a trend toward significant positive association was seen between consumption of LCD and odds of breast cancer in postmenopausal women; after controlling for several potential confounders, individuals in the third quartile of LCD score were 1.94 times more likely to have breast cancer than those in the lowest quartile (95% CI: 1.00, 3.76). This association strengthened after controlling for dietary variables (2.50; 1.18–5.32). Even after further adjustment for BMI, this association remained significant (2.64, 1.23–5.67). No significant relationship was observed in premenopausal women, either before or after controlling for confounders. Conclusion Adherence to LCD may be associated with increased odds of breast cancer in postmenopausal women. Prospective cohort studies are needed to confirm these findings.

Download Full-text

Role of Endocrine Disrupting Chemicals in the Occurrence of Benign Uterine Leiomyomata: Special Emphasis on AhR Tissue Levels

Asian Pacific Journal of Cancer Prevention ◽

10.7314/apjcp.2012.13.11.5445 ◽

2012 ◽

Vol 13 (11) ◽

pp. 5445-5450 ◽

Cited By ~ 13

Author(s):

Sepideh Arbabi Bidgoli ◽

Hoda Khorasani ◽

Heideh Keihan ◽

Alireza Sadeghipour ◽

Abolfazl Mehdizadeh

Keyword(s):

Endocrine Disrupting Chemicals ◽

Uterine Leiomyomata ◽

Tissue Levels ◽

Endocrine Disrupting

Download Full-text

Prenatal Exposure to Endocrine-Disrupting Chemicals and Subsequent Brain Structure Changes Revealed by Voxel-Based Morphometry and Generalized Q-Sampling MRI

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18094798 ◽

2021 ◽

Vol 18 (9) ◽

pp. 4798

Author(s):

Chao-Yu Shen ◽

Jun-Cheng Weng ◽

Jeng-Dau Tsai ◽

Pen-Hua Su ◽

Ming-Chih Chou ◽

...

Keyword(s):

Prenatal Exposure ◽

Brain Structure ◽

Phthalate Esters ◽

Endocrine Disrupting Chemicals ◽

Positive Association ◽

Orientation Distribution ◽

Voxel Based Morphometry ◽

Third Trimester ◽

Structure Changes ◽

Endocrine Disrupting

Previous studies have indicated that prenatal exposure to endocrine-disrupting chemicals (EDCs) can cause adverse neuropsychiatric disorders in children and adolescents. This study aimed to determine the association between the concentrations of prenatal EDCs and brain structure changes in teenagers by using MRI. We recruited 49 mother–child pairs during the third trimester of pregnancy, and collected and examined the concentration of EDCs—including phthalate esters, perfluorochemicals (PFCs), and heavy metals (lead, arsenic, cadmium, and mercury)—in maternal urine and/or serum. MRI voxel-based morphometry (VBM) and generalized q-sampling imaging (GQI) mapping—including generalized fractional anisotropy (GFA), normalized quantitative anisotropy (NQA), and the isotropic value of the orientation distribution function (ISO)—were obtained in teenagers 13–16 years of age in order to find the association between maternal EDC concentrations and possible brain structure alterations in the teenagers’ brains. We found that there are several specific vulnerable brain areas/structures associated with prenatal exposure to EDCs, including decreased focal brain volume, primarily in the frontal lobe; high frontoparietal lobe, temporooccipital lobe and cerebellum; and white matter structural alterations, which showed a negative association with GFA/NQA and a positive association with ISO, primarily in the corpus callosum, external and internal capsules, corona radiata, superior fronto-occipital fasciculus, and superior longitudinal fasciculus. Prenatal exposure to EDCs may be associated with specific brain structure alterations in teenagers.

Download Full-text

Urinary Equol is Associated with Bioavailable Testosterone but not Total Testosterone in Women

10.20944/preprints201906.0163.v1 ◽

2019 ◽

Author(s):

Hong-li Dong ◽

Feng Xiong ◽

Qing-wei Zhong ◽

Yi-hong Li ◽

Meng Liu ◽

...

Keyword(s):

Postmenopausal Women ◽

Menopausal Status ◽

Premenopausal Women ◽

Positive Association ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Total Testosterone ◽

Significant Positive Association ◽

Cross Sectional ◽

Bioavailable Testosterone

Little is known about the association between equol and bioavailable testosterone (BT) in adults. We examined the associations of urinary equol concentrations with serum total, bioavailable and free testosterone (FT), dehydroepiandrosterone sulfide (DHEAS), free androgen index (FAI) and sex hormone-binding globulin (SHBG) concentrations. This cross-sectional study included 1904 women aged 59.7 years. Urinary equol and serum sex hormone concentrations were measured. Overall, urinary equol tended to be inversely associated with bioactive forms of androgenic indices (BT, FT or FAI) but not with total testosterone (TT) or DHEAS. Urinary equol was also positively associated with SHBG. In multi-covariate-adjusted analyses stratified by menopausal status, graded and inverse associations between urinary equol and bioactive forms of androgenic indices (BT, FT and FAI) were observed in postmenopausal women (all p-trends <0.05), but not in premenopausal women. A significant positive association between urinary equol and SHBG was observed only in postmenopausal women. No significant associations were observed between urinary equol and TT or DHEAS in either group. A path analysis indicated that these associations of equol with androgens in postmenopausal women might be mediated by SHBG. Our findings indicated urinary equol exhibited graded and inverse associations with BT or FT but not TT in women.

Download Full-text

Exogenous hormone use, reproductive factors, and risk of intracranial meningioma in females

Journal of Neurosurgery ◽

10.3171/2012.9.jns12811 ◽

2013 ◽

Vol 118 (3) ◽

pp. 649-656 ◽

Cited By ~ 61

Author(s):

Elizabeth B. Claus ◽

Lisa Calvocoressi ◽

Melissa L. Bondy ◽

Margaret Wrensch ◽

Joseph L. Wiemels ◽

...

Keyword(s):

Body Mass Index ◽

San Francisco ◽

Body Mass ◽

Hormone Replacement ◽

Premenopausal Women ◽

Positive Association ◽

Age At Menarche ◽

Intracranial Meningioma ◽

Significant Positive Association ◽

Increased Risk

Object The 2-fold higher incidence of meningioma in women compared with men has long suggested a role for hormonally mediated risk factors, but specific mechanisms remain elusive. Methods The study included data obtained in 1127 women 29–79 years of age with intracranial meningioma diagnosed among residents of Connecticut, Massachusetts, North Carolina, the San Francisco Bay Area, and 8 Texas counties between May 1, 2006, and October 6, 2011, and data obtained in 1092 control individuals who were frequency matched for age group and geography with meningioma patients. Results No association was observed for age at menarche, age at menopause, or parity and meningioma risk. Women who reported breastfeeding for at least 6 months were at reduced risk of meningioma (OR 0.78, 95% CI 0.63–0.96). A significant positive association existed between meningioma risk and increased body mass index (p < 0.01) while a significant negative association existed between meningioma risk and current smoking (p < 0.01). Among premenopausal women, current use of oral contraceptives was associated with an increased risk of meningiomas (OR 1.8, 95% CI 1.1–2.9), while current use of hormone replacement therapy among postmenopausal women was not associated with a significant elevation in risk (OR 1.1, 95% CI 0.74–1.67). There was no association between use of fertility medications and meningioma risk. Conclusions The authors' study confirms associations for body mass index, breastfeeding, and cigarette smoking but provides little evidence for associations of reproductive and menstrual factors with meningioma risk. The relationship between current use of exogenous hormones and meningioma remains unclear, limited by the small numbers of patients currently on oral hormone medications and a lack of hormone receptor data for meningioma tumors.

Download Full-text

Preimplantation Exposure to Bisphenol A and Triclosan May Lead to Implantation Failure in Humans

BioMed Research International ◽

10.1155/2015/184845 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 13

Author(s):

Mu Yuan ◽

Ming-Zhu Bai ◽

Xu-Feng Huang ◽

Yue Zhang ◽

Jing Liu ◽

...

Keyword(s):

Bisphenol A ◽

Endocrine Disrupting Chemicals ◽

Positive Association ◽

Implantation Failure ◽

Chemical Structures ◽

Similar Chemical ◽

Endocrine Disrupting ◽

Estrogenic Properties ◽

The Relationship ◽

Human Fluids

Endocrine disrupting chemicals (EDCs) are chemicals that have the capacity to interfere with normal endocrine systems. Two EDCs, bisphenol A (BPA) and triclosan (TCS), are mass-produced and widespread. They both have estrogenic properties and similar chemical structures and pharmacokinetic features and have been detected in human fluids and tissues. Clinical evidence has suggested a positive association between BPA exposure and implantation failure in IVF patients. Studies in mouse models have suggested that preimplantation exposure to BPA and TCS can lead to implantation failure. This paper reviews the relationship between preimplantation exposure to BPA and TCS and implantation failure and discusses the remaining problems and possible solutions.

Download Full-text

Origin of Uterine Fibroids: Conversion of Myometrial Stem Cells to Tumor-Initiating Cells

Seminars in Reproductive Medicine ◽

10.1055/s-0037-1607205 ◽

2017 ◽

Vol 35 (06) ◽

pp. 481-486 ◽

Cited By ~ 7

Author(s):

Hoda Elkafas ◽

Yang Qiwei ◽

Ayman Al-Hendy

Keyword(s):

Stem Cells ◽

Molecular Mechanisms ◽

Endocrine Disrupting Chemicals ◽

Uterine Fibroids ◽

Premenopausal Women ◽

Tumor Initiating Cells ◽

Endocrine Disrupting ◽

Environmental Agents ◽

Gynecologic Tumors

AbstractUterine fibroids (UFs) are the most frequent gynecologic tumors, affecting 70 to 80% of women over their lifetime, Although these tumors are benign, they can cause significant morbidity and may require invasive treatments such as myomectomy and hysterectomy in premenopausal women at a cost of up to $34 billion per year. Many risk factors for these tumors have been identified, including environmental exposures to endocrine-disrupting chemicals such as genistein and diethylstilbestrol (and other environmental agents) resulting in hyper-responsiveness to hormone in the adult uterus and promotion of hormone-dependent UFs. Although the molecular mechanisms underlying the pathogenesis of UFs is largely unknown, a growing body of evidence implicates unfavorable early-life environmental exposure and multiple biological pathways express as potentially import contributors. In this article, we will review the role of genetic and epigenetics in the conversion of myometrial stem cells to tumor (fibroid) initiating cells, and their role in UF development.

Download Full-text