Endocrine disrupting chemicals and endometriosis

Endocrine disruptors and reproductive disorders


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.

Endocrine disrupting chemicals and endometriosis, Fertility and Sterility, Volume 106, Issue 4, Pages Pages 959–966, September 15, 2016.

laparoscopic surgery for endometriosis: fuschia_foot.

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;
  4. and 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.

Effects of Prenatal Environmental Exposures on the Development of Endometriosis in Female Offspring

Intrauterine diethylstilbestrol exposure and increased risk of endometriosis in descendance


Endometriosis has many hypothesized etiologies. Known risk factors include genetic predisposition, uterine outflow abnormalities, and iatrogenic causes. Of increasing concern is prenatal environmental exposures. However, the findings of studies investigating the relationships between prenatal environmental exposures and the development of endometriosis have not always been conclusive, and therefore, the relationships are debatable.

Effects of Prenatal Environmental Exposures on the Development of Endometriosis in Female Offspring, National Institutes of Health, NCBI PubMed PMID: 26905420, 2016 Feb 22.

This review presents a summary and analysis of the current studies that investigated the effects of prenatal environmental exposures on the development of endometriosis in female offspring.

Prenatal exposure to estrogenic substances (such as ethinyl estradiol and diethylstilbestrol) and environmental toxins (such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, polychlorinated biphenyls, and bisphenol A) may increase the incidence of endometriosis in female offspring. However, exposure to cigarette smoke may protect against the development of endometriosis in female offspring mainly because of its antiestrogenic effects.

Certain prenatal environmental exposures might result in the development of endometriosis in female offspring. In addition to known environmental exposures that predispose the development of endometriosis in adulthood, such as dioxin and radiation exposure (animal models), prenatal exposures are of increasing concern.

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Clear Cell Adenocarcinoma of the Ovary Associated with In Utero DES Exposure

A 45-year-old white woman was referred to an outpatient clinic with a self-discovered lump in the left lower abdominal quadrant


To our knowledge, this patient is the first clinical case featuring clear cell adenocarcinoma of the ovary that may be linked to diethylstilbestrol exposure in utero. We would like to emphasize that clear cell adenocarcinoma of the vagina and cervix, not the ovary, were previously shown to be sites for tumors in female offspring exposed prenatally to DES.

A 45-year-old woman presented with a self-discovered lump in the lower abdominal quadrant. She underwent surgery and staging that revealed clear cell adenocarcinoma confined to the left ovary. Foci of high-grade squamous neoplastic proliferation, inflammation, and a paratubal cyst were also present on the pathology specimen. Medical records established unequivocally that the patient’s mother received diethylstilbestrol therapy throughout the pregnancy. since clear cell cancers can develop, not infrequently, in foci of endometriosis, our patient’s pathology specimen was carefully inspected for endometriosis and none was found. Moreover, evidence linking prenatal DES exposure with chronic ovarian inflammation, paraovarian cysts, and high-grade squamous neoplastic proliferation in the genital tract has been accumulating. Although our patient is older than most patients in the Herbst cohort and a sporadic case of clear cell carcinoma cannot be excluded with certainty, all of the above changes were present in our patient’s pathology specimen. This further enhances our degree of suspicion on the causality between in utero DES exposure and the clear cell adenocarcinoma of the ovary in our patient.

Clear Cell Adenocarcinoma of the Ovary Associated With In Utero Diethylstilbestrol Exposure: Case Report and Clinical Overview, Medscape J Medv.11(1); 2009PMC2654676, 2009 Jan 7.

Our case is consistent with clear cell adenocarcinoma, probably related to diethylstilbestrol exposure in utero. Our case of probable DES-induced transplacental carcinogenesis more than 4 four decades after exposure reinforces the need for continued vigilance and routine gynecologic examinations in individuals prenatally exposed to this drug.

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Chemical Exposure linked to 1.4 Billion Euros in Women’s Health Care Costs

Endocrine-disrupting chemicals may raise risk of developing endometriosis, uterine fibroids

Washington, DC – Endocrine-disrupting chemicals may contribute to reproductive health problems experienced by hundreds of thousands of women, costing European Union an estimated €1.4 billion ($1.5 billion) a year in health care expenditures and lost earning potential, according to a new study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism, Female Reproductive Disorders, Diseases, and Costs of Exposure to Endocrine Disrupting Chemicals in the European Union.

Chemical Exposure Linked to 1.4 Billion Euros in Women’s Health Care Costs, The Endocrine Society, March 22, 2016.

The study examined rates of uterine fibroids – benign tumors on the uterus that can contribute to infertility and other health problems – and an often painful condition called endometriosis where the tissue that normally lines the uterus develops elsewhere in the body. The two conditions are common, with as many as 70 percent of women affected by at least one of the disorders.

Research has linked the development of uterine fibroids and endometriosis to chemicals found in pesticides, cosmetics, toys and food containers. Past studies suggest a byproduct of the pesticide DDT, a chemical known as DDE, can raise the risk of developing uterine fibroids. Another group of chemicals called phthalates, which are found in plastic products and cosmetics, have been tied to growing risk of endometriosis.

DDT and phthalates are known endocrine-disrupting chemicals (EDCs). EDCs can contribute to health problems by mimicking, blocking or otherwise interfering with the body’s hormones – the signaling system the body uses to determine how cells develop and grow. Unborn children are particularly vulnerable because exposure during key points in development can raise the risk of health problems later in life.

“The data shows that protecting women from exposure to endocrine-disrupting chemicals could substantially reduce rates of disease and lower health care and other social costs of these conditions”

said Leonardo Trasande, MD, MPP, Associate Professor of Pediatrics, Environmental Medicine & Population Health at NYU Langone Medical Center.

Female Reproductive Disorders, Diseases, and Costs of Exposure to Endocrine Disrupting Chemicals in the European Union, Endocrine Society, dx.doi.org/10.1210/jc.2015-2873, March 22, 2016.

The study is part of a series of economic analyses that found endocrine-disrupting chemical exposure may be costing the European Union upwards of €157 billion ($173 billion) a year. Prior studies in the series examined the costs associated with infertility and male reproductive dysfunctions, birth defects, obesity, diabetes, cardiovascular disease, and neurobehavioral and learning disorders.

To assess the economic burden of EDC exposure, a group of scientists convened a panel of global EDC experts to adapt existing environmental health cost models, relying on the Institute of Medicine’s 1981 approach of assessing the contribution of environment factors in causing illness. Based on the body of established literature, the researchers evaluated the likelihood that EDCs contributed to various medical conditions and dysfunctions.

Researchers only considered endometriosis and uterine fibroids in the analysis because there is robust data on their incidence and association with endocrine-disrupting chemical exposure. The researchers estimated that 145,000 cases of endometriosis and 56,700 cases of uterine fibroids in Europe could be attributed to exposure to endocrine-disrupting chemicals.

“Although these two gynecological conditions affect millions of women worldwide, we recognize that this analysis only reflects the tip of the iceberg,” “A growing body of evidence suggests EDC exposure is linked to a broader range of female reproductive problems, including polycystic ovary syndrome, infertility and pregnancy complications. These disorders also place a significant cost burden on women, their families and society as a whole.”

Trasande said.

The economic analysis included direct costs of hospital stays, physician services, and other medical costs. The researchers also calculated estimates of indirect costs such as lost worker productivity associated with these often painful disorders.

DiEthylStilbestrol in utero exposure and endometriosis incidence

Intrauterine DES-exposure and increased risk of endometriosis

In this 2004 study, the rate of endometriosis was 80% greater among women exposed to diethylstilbestrol in utero.
Eva Siba image © all rights reserved Special tribute to Marilyn who suffered severe endometriosis .

2004 Study Abstract

To investigate the relation between the fetal environment and Endometriosis.

Prospective cohort study.

Nurses’ Health Study II with 10 years of follow-up.

Eighty-four thousand, four hundred forty-six women aged 25-42 who had never been diagnosed with endometriosis, infertility, or cancer at baseline in 1989.

Incidence of laparoscopically confirmed endometriosis according to birthweight, prematurity, multiple gestation, diethylstilbestrol (DES) exposure, and having been breastfed.

During 566,250 woman-years of follow-up, 1,226 cases of laparoscopically-confirmed endometriosis were reported among women with no past infertility. After adjusting for age, calendar time, parity, race, and body mass index at age 18, we observed a linear increase in the incidence rate with decreasing birthweight (rate ratio [RR] = 1.3 for birthweight <5.5 pounds versus 7.0-8.4 pounds, 95% confidence interval [CI] = 1.0-1.8, P value, test for trend = .01). In addition, women who were born as one of a multiple gestation (i.e., twins or greater number) were at increased risk even after controlling for birthweight (RR = 1.7, CI = 1.2-2.5). The rate of endometriosis was also 80% greater among women exposed to diethylstilbestrol in utero (RR = 1.8, CI = 1.2-2.8). Neither premature delivery nor having been breastfed were associated with the incidence of endometriosis. None of these effect estimates were modified by infertility status at the time of endometriosis diagnosis.

The fetal environment is associated with subsequent laparoscopically confirmed endometriosis in this cohort of US women.

Sources and more information
  • In utero exposures and the incidence of endometriosis, Missmer SA1, Hankinson SE, Spiegelman D, Barbieri RL, Michels KB, Hunter DJ, Fertil Steril, NCBI PMID: 15589850, Dec 2004.
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Intrauterine diethylstilbestrol exposure and increased risk of endometriosis in adulthood

Early-life factors and endometriosis risk

This 2015 study results support the hypothesis that disruption of development during fetal and infant periods may increase the risk of endometriosis in adulthood. Endometriosis Awareness Month image by ALDE Communication.

2015 Study Abstract

To study early-life factors in relation to endometriosis risk in adulthood.

Population-based, case-control study. The Women’s Risk of Endometriosis study was conducted among female enrollees aged 18-49 years of a large, integrated healthcare system in western Washington State.

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.

Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the associations between intrauterine diethylstibestrol (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.

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.

Our results support the hypothesis that disruption of development during fetal and infant periods may increase the risk of endometriosis in adulthood.

Sources and more information
  • Early-life factors and endometriosis risk, Upson K, Sathyanarayana S, Scholes D, Holt VL., Fertil Steril. 2015 Jul 23. pii: S0015-0282(15)00469-0. doi: 10.1016/j.fertnstert.2015.06.040, NCBI PMID: 26211883, 2015.
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Endometriosis Rate estimated to be 80% greater in Women exposed to DiEthylSilbestrol in Utero

Endometriosis: If We Ignore It Will It Go Away?

Endometriosis: If We Ignore It Will It Go Away?Endometriosis occurs when endometrial cells grow where they shouldn’t – in places other than the uterus lining. It is estimated that up to 10% of women, or more, suffer endometriosis. Some studies have recently indicated that molecules from plastic, that break down in heat, can mimic estrogen, and may contribute to hormone problems, such as endometriosis. The rate of endometriosis is estimated to be 80% greater in women exposed to DiEthylStilbestrol in utero.

Read Endometriosis: If We Ignore It Will It Go Away?
by Kymberly Fergusson.

DES and Endometriosis

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