Endocrine Disruption

The Details

About The Endocrine System

The endocrine system of the body is made up of glands that secrete hormones. The pancreas, for example, is an endocrine organ that secretes the hormone insulin. The hormone/endocrine system is one system of communication within the body. Certain cells release hormones as a result of some signal (e.g., the beta cells in the pancreas release insulin when they sense that glucose levels in the blood are rising), and the hormone (in this case, insulin) travels through the blood to bind with hormone receptors (e.g., insulin receptors) on various cells. That triggers some effect, in this example, when insulin binds to a receptor, glucose can enter the cell. Almost all (or perhaps all) cells would have receptors for insulin, but only certain cells would have receptors for other hormones (e.g., estrogen or testosterone, etc.). The numbers and types of hormone receptors on cells change over time, and change depending on the concentration of the hormone in the blood, and on the stage of development of the organism. 

Endocrine organs include, among others, the pancreas, thymus, thyroid gland, and adrenal gland. Endocrinologists treat diseases of the endocrine system, such as diabetes and thyroid disease. There are many hormones in humans, estradiol, estrogen, testosterone, androgen, insulin, glucagon, glucocorticoid, thyroid hormones, and more. Vitamin D is also considered to be a secosteroid, a type of steroid hormone. 

Many hormones have diabetes-related effects, aside from insulin, including vitamin D, estrogen, testosterone, and more. The specific effects of hormones can depend on a lot of other things, including sex. Natural hormone levels in the body are linked to diabetes development. For example, higher testosterone levels (due to genetics) increases the risk of type 2 diabetes in women, but reduces the risk in men (Ruth et al. 2020). In older Hispanic men, lower testosterone levels were linked to a higher risk of developing diabetes from prediabetes, and higher estrogen levels were linked to insulin resistance. In post-menopausal Hispanic women, lower sex hormone-binding globulin levels were linked to a higher risk of developing diabetes from prediabetes (Persky et al. 2023). Estrogen is often thought to be protective against diabetes (De Paoli and Werstuck 2020). But interestingly a double-blind, randomized, placebo-controlled trial of post-menopausal women (who have lower natural estrogen levels than pre-menopausal women) found that those who took estrogen and progestin produced less insulin and had higher glucose levels than women who did not take these hormones (Depypere et al. 2020). This conflicts with the findings of earlier studies, and it is not clear why, but that does show that it may be complicated. Some authors note that in men, internal estrogens increase the risk of diabetes (in some but not all studies). In post-menopausal women, internal estrogens are linked to an increased risk of diabetes, but external estrogens (and progestins) with a lower risk (Persky et al. 2023). So the source of the hormone seems to matter. Androgen deprivation therapy, which lowers the amount of androgens (e.g., testosterone) in the body,  used to treat prostate cancer, increases the risk of diabetes in men (Gomaa et al. 2023).

Natural hormone levels during development are also linked to diabetes-related risk. For example, some women have high androgen levels (testosterone is an androgen) while pregnant. Their male offspring had a higher risk of pre-diabetes (although there was not association with obesity or type 2 diabetes) (Farhadi-Azar et al. 2023). 

A number of the chemicals considered here, including arsenic, some persistent organic pollutants (POPs) (including PCBs, dioxin, organotins, PBDE flame retardants, and PFASs), BPA, phthalates, some pesticides, probably heavy metals, and possibly nitrate, are considered endocrine disruptors. Please visit those pages for studies on these chemicals.

Most research on endocrine disruptors thus far has focused on the reproductive system, but the effects of these chemicals on other body systems are now under investigation. The immune system, the digestive system, the cardiovascular system, the central nervous system, metabolism, and fat (adipose) tissue are also targets of endocrine disrupting compounds (Hotchkiss et al. 2008).

Endocrine disruptors may interact with other mechanisms, such as epigenetics, oxidative stress, mitochondrial dysfunction, and more (Zhou et al. 2020).

Racial Disparities

While everyone is exposed to endocrine disrupting chemicals, some are more highly exposed than others. For example, ethnic and racial minorities tend to be exposed to higher levels of BPA, phthalates, parabens, and flame retardants than whites (James-Todd et al. 2016). In fact, there is substantial evidence that these disparities in exposure levels play a role in the disparities found in type 2 diabetes (Ruiz et al. 2018). Routine health care should monitor these exposures, and governments should take steps to limit them (Trasande and Sargis, 2024; Weiss et al. 2023).

Mixtures of Chemicals

While this webpage focuses on chemicals individually, we are all exposed to hundreds of endocrine disrupting compounds at the same time. What are the effects? We have no idea. One study studied exposure to low doses of 27 chemicals, similar to those found in humans. They found a variety of effects, including effects on weight and metabolism (Hadrup et al. 2016). We need more studies that address chemical mixtures or new methods to address this problem, and some are beginning to show up (e.g., see Lee and Jacobs 2015; Watt et al. 2016). One finds, for example, that a mixture of endocrine disrupting chemicals has numerous metabolic effects on mice (Le Magueresse-Battistoni et al. 2017).

Interestingly, mixtures of other endocrine disrupting chemicals can actually affect the levels of other endocrine disrupting chemicals. Single doses of triclosan, parabens, phthalates, or other phenols (and a combination of all of them) raised BPA (and estrogen) levels in mice, perhaps because they interfere with enzymes that metabolize estrogen (Pollock et al. 2018). For an article about this study, see Compound Interest: Assessing the Effects of Chemical Mixtures, published in Environmental Health Perspectives (Konkel 2017). 

The Endocrine Society's Statement concludes, "...there is sufficient evidence to conclude that some EDCs act as obesogens and others act as diabetogens." Also, "...animal studies indicate that some EDCs directly target beta and alpha cells in the pancreas, adipocytes, and liver cells and provoke insulin resistance together with hyperinsulinemia."

They also call for more research on EDCs and type 1 diabetes: "Studies relating EDCs and other contaminants to T1D are beginning to emerge, although they are still very preliminary... this is an important area that deserves further research and more studies in humans" (Gore et al. 2015).

In 2018-9 the journal Frontiers in Endocrinology published a group of articles as a Research Topic on Endocrine Disruptors and Metabolism, which covers the role of EDCs in everything from obesity to type 2 to type 1 diabetes (full disclosure: I wrote the article on type 1, Howard 2018).

A review of the evidence on endocrine disrupting chemicals and obesity notes that:

• • Endocrine disruptors are ubiquitous in the environment-- we are all exposed;

  • They have been shown to affect energy and metabolism;

  • They have been shown to affect body weight, fat content, fat cell development, glucose levels, obesity, insulin resistance, food intake, and more;

  • Their effects are most profound when exposure occurs during fetal development;

  • Their epigenetic effects may be significant for future generations;

  • Genes, poor diet, and sedentary behavior cannot fully explain obesity;

  • And finally, the evidence "provides a plausible basis for hypothesizing that endocrine disruptors are responsible for the rapid increase in obesity at the end of the last millennium." (Schneider et. al. 2014).

Among the various health effects of endocrine disruptors, diabetes and obesity are some of the best supported by evidence. For example, a review of recent research identifies "substantial human evidence" for the links between certain chemicals and diabetes or obesity: "Evidence is particularly strong for relations between perfluoroalkyl substances and child and adult obesity, impaired glucose tolerance, gestational diabetes, reduced birthweight .... Evidence also exists for relations between bisphenols and adult diabetes...; phthalates and ... childhood obesity, and impaired glucose tolerance." (Kahn et al. 2020). An editorial accompanying this article ("EDCs: Time to Take Action") states, "The science of endocrine disruption has also advanced considerably, but in the process far outpaced regulatory practices for control of EDCs. Overcoming this regulatory inertia is of paramount importance if citizen health and the environment are to be protected." (The Lancet Diabetes & Endocrinology, 2020). 

EDCs and Type 1 Diabetes

We do not have much evidence regarding type 1 diabetes and endocrine disruptors; it is a largely unexplored field. There is growing evidence, however, that endocrine disrupting chemicals can influence the risk of type 1. For example, some androgenic chemicals are linked to type 1 (Sakkiah et al. 2017).

First, we might ask whether natural hormones can influence the development of type 1 diabetes. There is evidence that they can. For example,  Gender differences are present in type 1 diabetes, and it is possible that sex hormones may influence the risk of developing type 1 diabetes in some way (Gale and Gillespie 2001). The incidence of type 1 diabetes in children peaks at puberty, a time of hormonal changes. Pregnancy, another time of hormonal change, can lead to gestational diabetes, later followed by type 1 or 2 diabetes. Stress may be a risk factor for type 1 diabetes, and while the mechanism is unknown, perhaps hormones released during stress could play a role. In addition, the hormone vitamin D appears to be protective against type 1 diabetes development. The role of height and weight as risk factors for type 1 diabetes may also involve hormones. The endocrine system is also affected by the gut microbiota and vice versa (Williams et al. 2020), which is another factor linked to type 1 diabetes (see the Diet and the Gut page).

In turn, all of these factors (puberty, pregnancy, stress, vitamin D, and height and weight), can be influenced by exposure to endocrine disrupting chemicals. For example, endocrine disruptors are a likely factor contributing to the earlier appearance of puberty, a possible accelerator of type 1 diabetes. 

It is clear to me, as someone with type 1 diabetes, that hormone levels can also influence blood glucose levels and blood glucose control day-to-day. Again, times of natural hormonal changes like puberty and pregnancy make it hard to control type 1 diabetes. Even the hormonal fluctuations during the menstrual cycle can affect insulin sensitivity in women with type 1 diabetes (see Brown et al. 2015).

We do not know, however, if chemicals that interfere with the endocrine (hormone) system contribute to the development of type 1 diabetes, or affect blood sugar management. The following sections provide some evidence that this possibility exists, although this hypothesis has not yet really been tested.

Because females are more susceptible than males to many autoimmune diseases, some researchers hypothesize that environmental estrogens could promote autoimmune disease (e.g., see Walker et al. 1996; Ahmed et al. 1999; Ortona et al. 2016). Gender does influence the behavior of the immune system, since sex hormones interact directly with immune system cells, although how these hormones might affect the development of type 1 diabetes is not known. Type 1 diabetes, unlike other autoimmune diseases, is not more common in females (Gale and Gillespie 2001).

In animals, some estrogenic endocrine disruptors have been found to promote autoimmunity. For example, Yurino et al. (2004) found that bisphenol A enhances autoantibody production in mice. Bisphenol A is an estrogenic compound. These researchers also found that the estrogenic pharmaceutical diethylstilbestrol (DES) had the same effects. The weakly estrogenic organochlorine pesticide chlordecone accelerates the development of autoimmune disease in mice. Its effects were similar to estradiol, but not identical (Wang et al. 2007) (described further on the persistent organic pollutants page). In animals, estrogen can cause the thymus to shrink, affect thymocytes, and promote autoimmunity; estrogenic chemicals may act similarly (Ahmed et al. 1999). 

DES was given to pregnant women decades ago to prevent miscarriage (it didn't work, but instead led to various health problems in these women's offspring-- as well as in their grandchildren (Kioumourtzoglou et al. 2018)). There is some limited evidence linking autoimmunity and DES in humans: women exposed to DES in utero seem to have a higher incidence of autoimmune disease, but only when various autoimmune diseases are grouped together (Ahmed et al. 1999). Yet a more recent study that followed these women over 25 years found that there was not an overall increase in autoimmune diseases in DES exposed daughters, although type 1 diabetes was not included in this study (only four autoimmune diseases were included). However, there was an increased risk of the autoimmune disease rheumatoid arthritis in women under 45, and a lower risk in those over 45 (Strohsnitter et al. 2010).

Estrogens also have been found to protect beta cells-- this may be one reason type 1 diabetes is not more common in women as compared to men. And, while puberty leads to an increased incidence of type 1 in boys, this is not necessarily the case in girls (Mauvais-Jarvis, 2017b).

Yet other chemicals that act via different, non-estrogenic pathways also have been shown to promote autoimmunity in animals. Thus estrogenic compounds are not the only compounds of concern. Phthalates, for example, can induce autoantibodies in mice, although the resulting health effects depend on the strain of mouse (Lim and Ghosh 2005). And, dioxin exposure during immune system development has been shown to result in changes suggestive of autoimmune disease in mice (Mustafa et al. 2008). Several phthalates are anti-androgens, and dioxin acts on multiple components of the endocrine system, via the aryl hydrocarbon receptor (AhR) (Hotchkiss et al. 2008). And, some chemicals can affect a number of receptors. Bisphenol A, for example, affects the activation of not only estrogen receptors, but also androgen and AhR receptors (Krüger et al. 2008).

The hormone vitamin D is also involved in the immune system, and may be protective against some autoimmune diseases, including type 1 diabetes (Norris 2001). Some chemicals may be able to affect vitamin D levels in animals. Lilienthal et al. (2000) hypothesized that since PCBs can affect other hormones, it might make sense that they could interfere with vitamin D levels. Their study found that PCBs did reduce vitamin D levels in rats. See the vitamin D page for more studies on vitamin D, type 1 diabetes, and chemical effects on vitamin D levels.

Up to 25% of patients with type 1 diabetes have evidence of thyroid disease, the most common autoimmune disease associated with type 1 diabetes (Umpierrez et al. 2003). Endocrine disruptors can affect the thyroid hormone (for a review of the main thyroid-disrupting chemicals (PCBs, perchlorates, brominated flame retardants, and phthalates), see Jugan et al. (2010)). Since thyroid levels during pregnancy are critical to proper fetal development, these thyroid disrupting chemicals are also important during development. Thyroid hormones are also important for glucose levels and metabolism. Thus prenatal exposure to thyroid disruptors are also linked to changes in glucose and metabolism in the offspring (Molehin et al. 2016).

There is a higher rate of type 1 diabetes among transgender and gender diverse youth than in the general population (Maru et al. 2021). We don't know why, perhaps it has to do with hormones, but it could be stress or something else involved.

Glucocorticoids are other hormones involved in the immune system. Disturbed glucocorticoid action is associated with a number of conditions, including autoimmune disease, type 2 diabetes, and obesity. Chemicals that can disrupt glucocorticoid action include PCBs, organotins, arsenic, dithiocarbamate chemicals (found in some pesticides and cosmetics), and more (Odermatt et al. 2006). The mechanisms by which early life exposure to glucocorticoid-disrupting chemicals (and other environmental factors) can lead to metabolic disease later in life is reviewed by Ruiz et al. 2020.

EDCs and Type 2 Diabetes

It is becoming clear that numerous endocrine disruptors are linked to the development of type 2 diabetes. The strongest evidence exists for persistent organic pollutants (see Lee et al. 2014; Taylor et al. 2013) and arsenic (Wang et al. 2014; Maull et al. 2012). There is growing evidence for many other endocrine disrupting chemicals as well (see pages on individual chemicals for details) (reviewed by Chevalier and Fénichel 2015; Fénichel and Chevalier 2017; Firmin et al. 2016; Kumar et al. 2020; Schulz and Sargis 2021). Endocrine disruptors also play a role in the development of insulin resistance (reviewed by Vanni et al. 2020).

Papalou et al. 2019 state, "EDCs unleash a coordinated attack toward multiple components of human metabolism, including crucial, metabolically-active organs such as hypothalamus, adipose tissue, pancreatic beta cells, skeletal muscle, and liver. Specifically, EDCs' impact during critical developmental windows can promote the disruption of individual or multiple systems involved in metabolism, via inducing epigenetic changes that can permanently alter the epigenome in the germline, enabling changes to be transmitted to the subsequent generations. The clear effect of this multifaceted attack is the manifestation of metabolic disease, clinically expressed as obesity, metabolic syndrome, diabetes mellitus, and non-alcoholic fatty liver disease. Although limitations of EDCs research do exist, there is no doubt that EDCs constitute a crucial parameter of the global deterioration of metabolic health we currently encounter."

A systematic review and meta-analysis of 49 studies from diverse populations found that both persistent (PCBs, dioxin, chlorinated pesticides) and non-persistent (BPA, phthalates) endocrine disruptors were associated with type 2 diabetes, impaired fasting glucose, and insulin resistance (Song et al. 2016). Endocrine disruptors are also implicated in complications and diseases that relate to type 2 diabetes, including atherosclerosis and cardiovascular disease (Helsley and Zhou, 2017; Kirkley and Sargis, 2014).

In fact, there is so much research on this topic (explored all over this website), that researchers are now calling these chemicals "metabolism disrupting chemicals" (Nadal et al. 2017). These chemicals are implicated not only in type 2 diabetes, but also metabolic syndrome, obesity, non-alcoholic fatty liver disease (NAFLD) (Foulds et al. 2017), and more. They can affect metabolism using a variety of mechanisms (Kassotis and Stapleton, 2019; Mimoto et al. 2017). Sex and gender differences affect the relationship between metabolic disrupting chemicals and obesity (reviewed by D'Archivio et al. 2024). For example, prenatal exposure to an EDC mixture had different links to body weight in girls vs boys (Svensson et al. 2024).

Estrogenic chemicals are linked to diabetes and obesity (Bardhi et al. 2024). Androgenic chemicals are also linked to diabetes (Sakkiah et al. 2017). It is clear that sex hormones play a role in type 2 diabetes (Tramunt et al. 2019), so it does make sense that chemicals that mimic these hormones do as well (Liu and Sun 2018). In fact sex hormones play a role in other types of diabetes as well, as well as obesity and metabolic syndrome, and in impaired fasting glucose and glucose intolerance (Mauvais-Jarvis 2018; Mauvais-Jarvis 2017). Early exposure to androgens during development may in fact be involved in the later development of insulin resistance, and help explain how numerous environmental factors (including chemical exposures, diet, stress, etc.) are linked to later insulin resistance (Puttabyatappa et al. 2020).

Researchers are looking into other mechanisms that may be involved as well. For example, some one study aimed to identify an environmentally relevant shared receptor target for endocrine and metabolism disrupting chemicals. The authors found a common mechanism of action through epidermal growth factor receptor (EGFR) inhibition for three diverse classes of metabolic disrupting chemicals (Hardesty et al. 2018). The insulin-like growth factor system is also involved in growth and metabolism, and may be a target for endocrine disrupting chemicals (Talia et al. 2020).

Some endocrine disruptors have been shown to increase the formation of fat cells. For example, both nonylphenol and DES promote the formation of fat cells in laboratory studies, and increase body weight in mice (Hao et al. 2012a, Hao et al. 2012b). Certain parabens, chemicals found in cosmetics and other consumer products, increase fat cell development and are potential obesogens (Hu et al. 2017; Hu et al. 2016; Pereira-Fernandes et al. 2013). Wastewater discharged from water treatment plants also contains endocrine disrupting compounds, and mice who drank this water gained more fat (Biasiotto et al. 2016). For studies on other endocrine disrupting compounds linked to obesity, see the individual chemical pages.

The effects of endocrine disruptors are important during development. For example, a study found that higher levels of environmental estrogens in the placenta were associated with higher birth weight in boys (Vilahur et al. 2013). Other studies have found exposure to endocrine disrupting chemicals to be associated with low birth weight (Birks et al. 2016).

There are other periods of life in which people are susceptible to endocrine disrupting chemicals as well, aside from early development. Menopause, when estrogen levels go down, is one such time. It seems that the body's hormone levels may interact in complex ways with the hormone-disrupting effects of chemicals to influence metabolism-related diseases such as diabetes and obesity (Julien et al. 2019).

The May 25, 2009 issue of the journal Molecular and Cellular Endocrinology published a special issue on the role of environmental endocrine disrupting chemicals in the development of obesity and diabetes. For example, Heindel and vom Saal (2009) propose that the recent increase in obesity is due to both nutrition and environmental chemical exposures in early life. Grün and Blumberg (2009) review the evidence that a variety of endocrine disrupting chemicals can influence fat formation and obesity. Newbold et al. (2009) review the mechanisms involved in endocrine disruption and obesity.

Numerous reviews also find that early-life exposure to endocrine disrupting compounds may play a role in the development of obesity (Botton et al. 2017; Braun 2017; Giulivo et al. 2016; Gutiérrez-Torres et al. 2018; Hall and Greco 2019; Heindel et al. 2017; Heindel et al. 2015; Holmes 2016; Janesick and Blumberg 2016; Kim and Lee 2017; Legler 2013; Lind et al. 2016; Maradonna and Carnevali, 2019; Nappi et al. 2016; Petrakis et al. 2017; Ribeiro et al. 2020; Russ and Howard 2016; Shafei et al. 2018; Wang et al. 2016).

One review focused on exposure to obesogens among Latinx/Hispanic youth in the Americas (Perng et al. 2021). It found a few consistent trends, which might also be applicable to people of other ethnicities. These findings include:

• • Prenatal exposure to POPs (PFAS, PBDEs, DDE/DDT) was linked to lower birthweight;

  • Prenatal exposure to POPs was linked to higher fat mass among boys but not girls;

  • Prenatal exposure to phthalates and bisphenols was linked to fat mass by gender as well, but inconsistently;

  • Childhood exposure to phthalates and bisphenols was linked to higher fat mass in girls but lower in boys;

  • In general, early life exposure to multiple chemicals is linked to weight-related measures in children.

While we wait for them to figure this out, we are experimenting on ourselves (but without an unexposed control group). For example, some scientists analyzed 65 compounds that migrate from polycarbonate plastic baby bottles (into milk), and found that 53 of them showed some endocrine activity (Simon et al. 2016). Exposing babies to these chemicals is just not ethical.

In the European Union, meanwhile, they are trying a little harder to regulate endocrine disrupting chemicals, for example through the REACH program, which stands for Registration, Evaluation, Authorisation and Restriction of Chemicals. Interestingly, one expert workshop recently provided recommendations on how to measure insulin in toxicology studies (Kucheryavenko et al. 2019). I've never seen diabetes-related measurements included in formal regulatory programs before. A project within EU-funded Partnership for the Assessment of Risks of Chemicals (PARC) is aimed at developing novel in vitro methods for the detection of metabolic disruptors (Braeuning et al. 2023).  

Some scientists advocate for redoing regulations on EDCs. They state, "In the EU, general principles for EDCs call for minimisation of human exposure, identification as substances of very high concern, and ban on use in pesticides. In the USA, screening and testing programmes are focused on oestrogenic EDCs exclusively, and regulation is strictly risk-based. Minimisation of human exposure is unlikely without a clear overarching definition for EDCs and relevant pre-marketing test requirements. We call for a multifaceted international programme (eg, modelled on the International Agency for Research in Cancer) to address the effects of EDCs on human health-an approach that would proactively identify hazards for subsequent regulation." (Kassotis et al. 2020).

Note that standard toxicology tests are not necessarily good enough to detect the metabolism disrupting effects of endocrine disrupting chemicals (Attema et al. 2024).

A review discusses ways to regulate endocrine disruptors and the issues and complications involved (Duh-Leong et al. 2023).