Women’s Health: Effects of Endocrine Disruptors

3 Essentials

What are endocrine disruptors?

Endocrine disruptors are chemicals, which, through inappropriate exposure, interfere with hormones like estrogen and alter their signaling pathways. Hormones regulate development, metabolism, reproduction, immunity and behavior. Endocrine disruptors can have life-long effects and may affect the next generation. Most endocrine disrupting chemicals are made by humans. When endocrine disrupting chemicals are absorbed through the skin, breathed or ingested through food or drink, they essentially mimic hormones in the body and either block the natural signals or cause hormonal signals when they should not occur. The result is that the body’s natural hormonal balance is disrupted causing numerous health problems. The World Health Organization (WHO) defines EDCs as substances that alter one or more functions of the hormone system and, consequently, cause adverse health effects in an intact organism or its progeny or (sub) populations (World Health Organization, 2019).

Endocrine disrupting chemicals are not broken down quickly in the environment. That is why they are used in products and food production. Companies add these chemicals to the things you buy in the store to extend their shelf lives. Unfortunately, endocrine disruptors also take a long time to break down in the body, meaning that your body has a difficult time getting rid of them—giving them more opportunity to disrupt a normal balance.

Endocrine disruptors can:

Mimic or partly mimic naturally occurring hormones in the body such as estrogens (the female sex hormone), androgens (the male sex hormone) and thyroid hormones, potentially producing overstimulation.
Bind to a receptor within a cell and block the endogenous hormone (the body’s own hormone) from binding. The normal signal then fails to occur and the body fails to respond properly. Examples of chemicals that block or antagonize hormones are anti-estrogens and anti-androgens.
Interfere or block the way natural hormones or their receptors are made or controlled, for example, by altering their metabolism in the liver.
Trigger autoimmune thyroid disorders, resulting in Graves’ Disease or Hashimoto Thyroiditis, as well as other autoimmune diseases. [1] Thyroid hormones are essential for the functioning of the female reproductive system. They modulate the metabolism and development of ovarian, uterine and placental tissues.

Where Do They Come From?

There are thousands of endocrine disrupting chemicals and we are exposed to them daily. They are in our food, the packaging it often comes in, beauty products, household cleaners, water, soil, air and even in the dust that gathers on our bookshelves.

Alkyphenols are used as emulsifiers, found in detergents, antistatic agents, plastic additives and pesticides. Found in water from sewage treatment, river water, drinking water from polluted ground waters, food grown from land contaminated or irrigated with contaminated water. High concentrations are found in seafood in Asia, Europe, North America. In Taiwan, the highest concentrations are found in salmon and oysters. There are high quantities in vegetables reported in Sweden and Spain. Florida has the highest concentrations in carrots, pumpkins, apples and citrus. [2]
Atrazine: An herbicide used to control weeds and grass. Found in drinking water.
Bisphenol A (BPA): A chemical used to harden plastics. Found in plastic bottles, the inside lining of some canned foods, medical devices, hygiene and cleaning products, dental sealants, and in the water, dust and air. At high temperatures, i.e. placing plastic in the microwave or leaving your water bottle in a hot c, will increase the release of BPA. BPA binds to the estrogen receptor. BPA is classified as a CMR, carcinogenic, mutagenic or toxic to reproduction. [3]
Dioxins: A family of toxic chemicals. Found in the environment as a byproduct of industrial processing; found mainly in fish, seafood, meats, eggs and cheese.
Dichlorodiphenyltrichloroethane (DDT): DDT is a lipid-soluble pesticide that has been banned in many countries. However, DDT persists in the environment. It is still being used in developing countries. The main source of exposure is through food. It is a part of the food chain with the primary source being fish and animals that are herbivores. DDT accumulates in food rich in fat, such as fish, meat, milk, milk products and oil.
Flame Retardants: A group of chemicals added to many manufactured items. Found in fabrics, plastics, surface coatings, furniture such as sofas and mattresses, and baby products.
Parabens: Anti-microbial preservatives. Found in personal care products, such as skin care, makeup, shampoos and conditioners, soaps, deodorants and lotions to stop bacterial growth. They are absorbed through the skin. Weak estrogen mimickers that bind to estrogen receptors.
Perchlorate: An industrial chemical. Used in rocket propellant, firework and road flares, and can end up in drinking water.
Perfluoroakyl and polyfluoralkyl (PFAS): PFAS comprise a large family of human made fluorinated chemicals that are ubiquitous environmental toxicants. Specific members of this family of chemicals are found in non-stick cookware, food packaging materials, stain- and water-resistant coating for clothing, furniture and carpets (Scotchgard and GoreTex), cosmetics and personal care products. PFAS are also present in fire-fighting foams (or aqueous film-forming foam, AFFF) widely used in military bases for crash and fire training.
Pesticides: Substances used to destroy insects and other harmful organisms. Used in farming and food production. Exposed to pesticides through your occupation, dietary and environmental exposure (water, soil, air).
Phthalates: Chemicals widely used in production. Found in plastics, scented beauty products and household cleaners—and many other everyday items, including nail polish, carpeting and even your car’s steering wheel. Found in shower curtains and raincoats.
Others include: Arsenic, glycol ethers, lead, mercury, PCBs (banned in 1980, but still present in the food supply), and polybrominated biphenyl (PBB).

How They Affect You

Endocrine disruptors can have a negative impact on many functions of the body, but they are most harmful to the thyroid, sex hormones and reproductive system. More specifically, endocrine disruptors can interfere with puberty—causing it to occur earlier in girls. Increased levels of endocrine disruptors in the female body have been associated with conditions of estrogen dominance, including menstrual cycle irregularities, endometriosis, uterine fibroids, polycystic ovarian syndrome and infertility/subfertility. In a recent study, 27 genes commonly found to be dysregulated in ER-positive and ER-negative breast cancer were found to interact with endocrine disrupting chemicals.

Endometriosis is a painful disorder in which tissue that normally lines the inside of the uterus, the endometrium, grows outside the uterus. It typically affects the ovaries, fallopian tubes and the uterus. The endometrial tissue acts like normal endometrial tissue- it thickens, breaks down and bleeds with each menstrual cycle. When the tissue cannot exit the body, it becomes irritated, develops adhesions and scar tissue. which can be painful and affect a woman’s quality of life. It can also affect fertility. Endometriosis is an estrogen dependent condition that affects 10-15% of women of reproductive age. A systemic review of epidemiological data showed some evidence that there is an association between bisphenol A (BPA), phthalate esters (PE), organochlorinated environmental pollutants or persistent organochlorinated pollutants (POPs) and the prevalence of endometriosis.

Di-2-ethylhexyl phthalate (DEHP) is the most common member of the class of phthalates. DEHP is a widely used plasticizer in cosmetics, personal care products, furniture, rainwea and food contact material. An association of PEs and endometriosis were found in studies inclusive of American, Indian, Taiwanese and Korean populations.

POPs are a group of chemicals including dioxins, PCBs and organochlorinated pesticides. POPs are ubiquitous in the environment, have estrogenic properties, lipophilic and accumulate with age and exposure. Dioxins and dioxin like compounds are a POP that are found predominantly in the soil and food, especially dairy products, meat, fish and shellfish. They are stored in fat cells. Studies suggest exposure to dioxins are associated with endometriosis.

Polychlorinated biphenyls (PCB) are associated with endometriosis. Ninety percent of exposure to PCBs occurs through the diet. According to the EPA, contaminated fish are a persistent source of PCBs. PCBs build up in fish and animal fat.

Organochlorinated pesticides (OCP) belong to the class of persistent organic pollutants that have a high persistence in the environment. The relationship between OCPs and endometriosis are affected by exposure, genetics, age, BMI. [4]

Endometrial Cancer and Leiomyoma: The hormone disruptor alkylphenol (commonly referred to as an xenoestrogen) and its metabolites, specifically, NP (nonylphenol) and OP (octylphenol), may be associated with endometrial cancer and leiomyoma. Endometrial cancer is the most commonly diagnosed cancer of the female genital tract. NP acts like estrogen, binds to the estrogen receptor and displaces estradiol. The metabolites NP and OP are more toxic than alkylphenols. The health concerns are related to the persistence and bioaccumulation of NPs and OPs. [5]

Polycystic Ovarian Syndrome (PCOS): PCOS is a hormone disorder that affects women of reproductive age. Women with PCOS have irregular menstrual periods or excess androgen levels, i.e. testosterone or DHEA and polycystic ovaries. Infertility is a common result of PCOS.

PCOS is the most common endocrine disorder in women of reproductive age. A case-controlled study in China showed that patients with PCOS( polycystic ovarian syndrome) had higher levels of BPA (Bisphenol A) and PAEs (phthalates). [6] The woman’s ability to clear these environmental disruptors was interrelated with certain SNPs or mutations of the enzymes. Other studies show that women exposed to BPA have a higher luteinizing hormone/follicle-stimulating hormone relationship. [7]

PCOS and Insulin Resistance: There is growing evidence of the role of endocrine disruptors in obesity and diabetes. DEHP (di-2-ethylhexyl phthalate) exposure has been related to insulin resistance in adolescents. Insulin resistance is a known factor in PCOS. A study in Turkey with 63 adolescent girls found a significant correlation between DEHP and insulin resistance and dyslipidemia. This suggested that DEHP may have a direct or indirect effect on metabolism in adolescent girls. The association between DEHP and insulin resistance was stronger in the PCOS group. [8]
Another study showed that organic solvents found in indoor decorations affected insulin sensitivity negatively in PCOS women. [9]

The literature suggests that there is an interaction of Endocrine Disruptors, AGEs (Advanced glycation end products) and hormones in PCOS. Higher levels of the following EDCs have been found in PCOS. These include PBCs, organochlorine pesticides, perfluorooctanoate, perfluorooctane sulfonate, polycyclic aromatic hydrocarbons. AGE’s are thought to affect reproductive function in preovulatory follicles through chronic inflammation and oxidative stress. Women with PCOS typically have insulin resistance and many are overweight. Environmental toxins have been shown to be involved in the pathophysiology of both obesity and the onset of type 2 diabetes. Insulin resistance and visceral obesity are present in 30-75% of women with PCOS.

Ovarian Cancer: There is some evidence that there is a link between endocrine disruptor chemicals (EDCs) and ovarian cancer. The EDCs identified include pesticides, triazine herbicides, organophosphate diazinon, triclosan and methoxychlor (MXC). BPA has been shown to interfere with the synthesis of reproductive hormones which results in a hormonal imbalance. There is a molecular similarity between environmental toxins and endogenous hormones that may result in hormonal and metabolic disruption. This may affect both ovarian cancer and PCOS. Patients diagnosed with PCOS, who are exposed to environmental toxins may be at increased risk of ovarian cancer. EDC exposure may increase hyperandrogenism and ultimately promote cell proliferation and tumor growth. Oxidative stress and insulin resistance, prominent in PCOS may contribute to DNA damage and epigenetic modification. Finally, EDCs may be a contributor to ovarian cancer, a complex disease that includes a positive family history, endometriosis, increased number of ovulatory cycles, increased age, high fat diet and obesity, plus advanced glycation end products. [10]

Menstrual Cycle Irregularity: A study in China showed that the biomarkers of organophosphates were associated with menstrual irregularity in preconceptual women in Shanghai. There were 627 women included in the study. Organophosphates are the most heavily used pesticides in China. [11]

Menstrual irregularity, delayed menarche, premature ovarian insufficiency and early menopause: Observational studies point to the effect of PFAS on women’s hormone. PFAS, perfluoroakyl and polyfluoralkyl substances are a ubiquitous toxicant that has been found in contaminated drinking water in the United States and globally. Experimental studies have shown that PFAS exposure is associated with the depletion of ovarian reserve. Research suggests that PFAS targets the ovary, thus affecting folliculogenesis (formation of the follicle) and steroidogenesis (production of hormones by the ovaries). Such far reaching effects appear to have significant impact on the health of girls and women throughout the life cycle. More research is necessary for causal connections. [12]
A recent study showed that PFAS exposure was associated with increased age at menarche and irregular menstrual periods in young women. Levels of PFAS in blood have been associated with decreased serum levels of estradiol, progesterone, sex hormone-binding globulin, follicle-stimulating hormone and testosterone.

Times in life where a woman’s breast is vulnerable to environmental exposure: Susceptibility to environmental exposure occurs during puberty, implantation, fetal growth, pregnancy and aging. Exposure during these times of susceptibility are hypothesized to increase the risk of breast cancer. Epidemiological studies show evidence that environmental exposure during puberty increases the risk of breast cancer as an adult. Water, air pollution and endocrine disrupters have an accumulative effect over the course of a woman’s lifetime. Endocrine Disrupters play a role in regulating growth and development by binding to hormone receptors. Bisphenol A (BPA) is an endocrine disruptor that is used to soften plastics. BPA, which has been found in human blood, placenta, fetal liver and breast milk, is associated with early puberty. A recent study showed that 27 genes found to be dysregulated in ER-positive and ER-negative cancer interact with endocrine disrupters.

Parabens are preservatives used to extend the shelf-life of products such as body creams, antiperspirants, sunscreen, lotions and shampoos and have been associated with the increased risk of cancer. It has been suggested that parabens in body care formulations are involved in breast cancer.

Phthalates impair endocrine function through the steroid receptors. These interactions are associated with early puberty and infertility in women. Phthalates are found in hair cosmetics, deodorants, nail polish and lotions. [13]

Breast cancer affects 2.1 million women per year. According to the WHO this is 15% of deaths in women. Breast cancer is a complex disease and many factors may affect a woman, such as age of onset, race, early menarche, late menopause, genetics, alcohol, smoking and endocrine disruptor chemicals. Some EDC that contribute to breast cancer include phthalates, pesticides, DDT and phenols. Phthalates are used in the manufacturing of cosmetic products, deodorants and personal care products. Phthalate esters are endocrine disrupters that affect reproductive health. Endocrine disrupters interfere with the synthesis, secretion, transport and binding of hormones. Bisphenol and other endocrine disruptors are known to cause cell proliferation, angiogenesis and affect changes in apoptosis. Endocrine disruptors can cause resistance to chemotherapy by releasing proinflammatory factors. Phthalates are found worldwide in cosmetic products. Phthalate esters are known to promote tumorigenesis.
Since phthalates mimic estrogen, increased exposure may lead to a hormone dependent breast cancer. [14]

Food and Endocrine Disruptors: Endocrine disruptor chemicals (EDCs) are present in fish. Seafood bioaccumulates EDCs. Levels of EDCs vary depending on the level of contaminants in their home waters. Soy isoflavones were observed in processed fish. Freshwater fish also have detectable levels of EDCs. A study done in Spain with fish from four rivers showed fish to have 10 EDCs including parabens, bisphenols, hormones, organophosphorus flame retardants, triclosan and BPA. Fish intake has been associated with reduced maternal fecundability among couples trying to get pregnant.

Growth promoting hormones given to farm animals increase hormone exposure to those humans consuming this meat. Hormones include 17B-estradiol, progesterone and testosterone. BPA (plasticizer) is found in raw cow’s milk. Organic free range and battery produced hen eggs were reported to have phthalic acid esters.

Prepubertal children are known to be exposed to endocrine disrupters through milk, meat and eggs. This consumption could lead to an alteration in their endocrine metabolism.
Recommendation is to consume these foods in moderation.

Packaged food is increasingly becoming popular as consumers are taking less time to prepare food. The packaging materials have endocrine disrupters as their constituents. The most common EDC leachates (meaning EDCs leach out from the packaging materials) include BPA and phthalates, (DEHP), and dibutyl phthalate. The United States Environmental Protection Agency has given BPA the third highest priority in terms of its toxic profile. BPA is used in making resins that are used in food containers, containers for mineral water, food, beverage can linings and plastic baby bottles. BPA migrating to food is harmful to humans. BPA is associated with reproductive, developmental and metabolic effects.

DEHP which is a member of the phthalate (plasticizers) group of chemicals is an estrogen agonist. This means it activates the receptor and affects the expression of many genes. Some of these genes are critical for fetal development and may result in the loss of pregnancy. DEHP is found in milk products, fish, seafood and oils.

Food additives have been reported to be endocrine disrupting chemicals. In a 2014 study it was reported that 167 additives have estrogenic activity. Seventy five percent of these additives were estrogen receptor agonists and 25% were estrogen antagonists, which means they blocked the estrogen receptor. In 2018 it was reported that the use of direct and indirect additives caused obesity, thyroid hormone disruption, carcinogenicity, neurodevelopmental disorders and decreased birth weight.

There are more than 1000 pesticides used across the world and 105 of them are known to be endocrine disruptors. Humans are exposed to pesticides through food. One of the most potent pesticides is dichlorodiphenyltrichloroethane (DDT). DDT is banned in many countries. It is still used in developing countries. DDT continues to persist in the environment. DDT is a lipid soluble pesticide and is found in milk and milk products, meat, fish and oil. A study from Pakistan analyzed 137 food items for DDT and found to be present in 96% of the samples. Fish has the highest levels of DDT. DDT exposure affects the health of women through reproductive abnormalities, germline cancers (caused by mutations that affect reproductive cells), early puberty and reduced pregnancy rate. [15]

How To Protect Yourself

Despite emerging research that endocrine disruptors may be linked to various health problems, they are still used in manufacturing and food production. Even the ones that have been banned exist in our soil and water today. Although it is impossible to avoid endocrine disruptors completely, there are simple things you can do to limit your exposure. Pregnant and nursing mothers, parents of small children and pre-pubertal girls should pay extra attention as these are the stages when the young are extra vulnerable.

Choose fresh, unpackaged foods, organic when possible and wash fruits and vegetables. This will help limit your exposure to endocrine-disrupting pesticides and herbicides. Follow EWG’s “Dirty Dozen” list found to guide you in which produce items are more important for buying organic.
Before cooking fish, remove the skin and fat of the fish, along with internal organs. Let them drain and avoid or reduce fish drippings. Avoid fried fish. Frying seals in chemical pollutants that may be in the fish’s fat. Recommend grilling or broiling fish to drain the fat.
Avoid drinking out of plastic water bottles. Plastic water bottles contain BPA which leaches into the water (and leaches even more when it becomes warm such as leaving a plastic water bottle in a hot car). Instead, drink out of glass or sterling silver glasses and containers which are easy to transport and take with you on the go. This is also a great option to take with you to a coffee shop to use instead of the paper coffee cups which contain BPA in the lining and plastic lids that leach with the heat of the coffee or tea.
Choose safer personal care products. Choose fragrance-free and paraben-free cosmetics, beauty products, shampoos, conditioners, soaps and lotions. Refrain from wearing perfumes. This will reduce your exposure to phthalates, parabens and other endocrine disruptors. To help select safer products visit the Environmental Working Group Skin Deep database: https://www.ewg.org/skindeep/
Cook with stainless steel, cast iron, titanium or ceramic pans rather than non-stick. Not only are these pans free of PFCs, but they often last longer and give you better tasting foods.
Filter your water. Filtering your drinking water will reduce arsenic, atrazine, perchlorate, lead and the presence of other endocrine disrupting metals. If you can, add water filters to all of your home faucets, including the bath and shower because you absorb disruptive chemicals through your skin in addition to drinking them.
Vacuum your house with a HEPA filter. Since so many endocrine disruptors are found in dust, a HEPA filter on your vacuum cleaner can help reduce dusty toxins in your home. Keeping your home clean and tidy on a regular basis will also help your air stay cleaner and healthier.
Buy fewer plastics in general. BPA and other endocrine disruptors can leach out of any kind of plastic, including children’s toys, plastic wrap and all the various plastic recyclables, especially #3, #6 and #7 in the United States. Don’t forget that your skin is an organ, so holding, touching and using plastics will increase your exposure to the various endocrine disruptors. Store food in glass containers and buy wooden and cloth toys for children. Avoid plasticware.
Clean with safer products. Cleaning products are frequently filled with industrial chemicals that disrupt your hormones. So instead, try cleaning with greener alternatives or blend up your own using natural, non-toxic ingredients like old-fashioned soap, lemon, vinegar, etc. Visit the EWG’s Guide to Healthy Cleaning: https://www.ewg.org/guides/cleaners
Avoid Bank and Cash Register Receipts. The coating on most cash-register receipts contain endocrine-disrupting BPA, so the less time you spend touching them the better. If you don’t need the receipts, leave them at the store. If you do need them for tax or business purposes, wear gloves to limit exposure when handling them.
Reduce the amount of conventionally farmed meat, poultry and dairy products in your diet. Conventionally farmed animal foods contain disruptive antibiotics, hormones and industrial chemicals. To reduce exposure, if you eat animal products, look for organic, grass-fed and free-range products from small or local farms that are committed to raising animals using methods that are healthier for both the animals and the humans who consume them.
Avoid eating high-mercury fish. Shark, swordfish, king mackerel, marlin, tuna (Big Eye, Ahi) and tilefish are high in mercury and other heavy metals which disrupt hormonal balance and function. If you eat fish, limit consumption to low-mercury fish like anchovies, herring, sardines, whitefish or one of the other low-mercury fish recommended by the Natural Resources Defense Council or Environmental Working Group. https://www.ewg.org/research/ewgs-good-seafood-guide. If you are eating salmon, avoid eating farmed salmon which contains dioxins.

Work with a naturopathic doctor / naturopath to help you assess for environmental pollutants and to understand how they may be affecting your health. The information on this website is a guide for ways to protect you and your family from environmental pollutants. It is not meant to replace advice from a healthcare professional.

Choose fresh, unpackaged foods, organic when possible and wash fruits and vegetables.
Avoid drinking out of plastic water bottles.
Choose personal care products that are free of parabens, Bisphenol A (BPA) and Phthalates.

Additional Key Recommendations

Cook with stainless steel, cast iron, titanium, or ceramic pans rather than non-stick.
Filter your water.
Buy fewer plastics in general.
Vacuum your house with a HEPA filter.
Clean with your own blend of natural, non-toxic ingredients such as soap, lemon, vinegar.
Avoid Bank and Cash Register Receipts.
Reduce the amount of conventionally farmed meat, poultry, and dairy products in your diet.
Avoid eating high-mercury fish, Shark, swordfish, king mackerel, marlin, tuna (Big Eye, Ahi) and tilefish.
Eat low-mercury fish like anchovies, herring, sardines, whitefish, wild salmon, tilapia, scallops…

References

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