Marianne Marchese, ND
Introduction
Women’s health conditions seem to be dominated by women’s hormones. Estrogen, testosterone, and progesterone are the main players. Thyroid hormones, cortisol, and DHEA have a role as well. These hormones are involved in the development of common conditions affecting women such as fibroids, endometriosis, and PCOS. Environmental toxins that women are exposed to everyday in low doses alter women’s hormones. Toxins can be present in small amounts in our food, water, and cleaning and grooming products. Research has repeatedly proven the link between toxins and women’s hormonal conditions. The main culprits are bisphenols, phthalates, pesticides, and some heavy metals. It is important for patients and practitioners to understand the link between the toxins and women’s hormonal issues, such as fibroids, in order to prevent and treat these conditions.
Fibroids
Uterine leiomyomas, also called fibroids, are an estrogen-driven condition affecting numerous women in the US. They are benign proliferations of smooth muscle cells of the myometrium. They are most common in the reproductive years and regress in menopause as estrogen levels decline. Fibroids account for a majority of hysterectomies done in the US. But not all fibroids cause symptoms or require surgery. Generally, they become a problem when their location results in heavy bleeding or spotting affecting a woman’s quality of life. They can be located in the muscular wall of the uterus, called intramural, just beneath the uterine serosa, called subserosa, and beneath the endometrium, called submucosal. Some can be pedunculated, meaning it remains connected to the uterus with a stalk.1,2
Fibroids are hormonally responsive to both estrogen and progesterone. Risk factors include race (more prevalent in African American women), early menarche, nulliparity, perimenopause, alcohol use, oral contraceptive use, and hormone replacement therapy—the theme being hormones. Estrogen can induce their growth as seen during pregnancy. It is believed estrogen may stimulate the production of progesterone receptors in the myometrium; and, then, progesterone stimulates the production of growth factors causing the growth of fibroids.1,2
The exact mechanism is unclear. The influence of endocrine-disrupting chemicals (EDCs) is, however, becoming clear.
Bisphenol-A (BPA)
BPA is a known endocrine-disrupting chemical present in the lining of canned food, soda and beer cans, reusable plastic beverage bottles (Polycarbonate plastic #7), dental sealants, and paper receipts from a cash register. Women are exposed daily without knowing its impact on hormonal health. A recent study measuring urinary concentrations of BPA in almost 500 women with fibroids compared to women without fibroids showed a clear connection.3 Urinary BPA levels were higher in women with fibroids compared to those without fibroids. Studies trying to determine the mechanism of action of BPA on fibroid growth and development have shown that BPA promotes the growth of fibroid cells and the expressions of estrogen receptor alpha (ERa), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF).4 Some studies on the link between BPA and fibroids show inconsistent results. A 2013 study looking at blood BPA levels and fibroids showed there were no differences in the blood BPA level among women with and without fibroids. However, some statistical differences were present among subgroups classified by the size of the uterine fibroid; the more severe the uterine fibroid was, the higher the level of BPA.5
Phthalates
Phthalates are known endocrine-disrupting compounds present in many consumer products. They are used in vinyl flooring, plastic clothes and household items (raincoats, shower curtains and placemats), soaps, shampoos, hair sprays, nail polishes, garden hoses, inflatable toys, medical tubing, and some children’s toys. They are in anything fragranced such as some perfumes, deodorants, laundry detergents, and more. Phthalates are in food items such as meats and cheeses, plastic food storage containers, and wraps. They are hard to avoid and harder to identify on a label because there are many forms, including DBP (dibutyl phthalate), DINP (diisononyl phthalate), DEP (diethyl phthalate), DEHP (di 2-ethylhexl phthalate), DMP (dimethyl phthalate), BBP (benzyl butyl phthalate), DNOP (di-noctyl phthalate), and DIDP (diisodecyl phthalate). Phthalates are linked to many hormonal conditions, including uterine fibroids.
A small study done in 2016 looked at the urinary concentration of 16 phthalate metabolites in 57 women with and without uterine fibroids. DEHP was significantly associated with fibroids.6 A second small study in 2016 again showed phthalates linked to fibroids. Urinary levels of the phthalate monoesters MiBP, MnBP, MEHP, MEHHP, MECPP, DEHP, and DBP were elevated in women with fibroids compared to controls.7 These were small, case-controlled studies, and critics want larger studies to prove a correlation. A 2010, cross-sectional study was done of four urinary phthalate metabolites in relation to uterine fibroids among 1,227 women, age 20-54, from three cycles of the National Health and Nutrition Examination Survey (NHANES), 1999-2004. This was a large population-based study that showed an association between the DBP phthalate metabolite MBP and uterine fibroids.8
Persistent Organic Pollutants (POPs)
Persistent organic pollutants include chemicals used as industrial solvents or lubricants and their byproducts such as polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), and dioxins. POPs also include pesticides such as methoxychlor, chlorpyrifos, and dichlorodiphenyltrichloroethane (DDT). Many POPs are known endocrine-disrupting compounds altering hormone function or synthesis and may bind to estrogen receptors affecting hormonally mediated conditions. A 2015 study looked at the link between persistent organic pollutants and fibroids. Adipose and serum samples from 473 women with fibroids showed an association between serum dichlorodiphenyldichloroethylene (DDE), a metabolite of DDT, and adipose polychlorinated biphenyls (PCBs).9 This confirms results of previously published studies linking POPs and fibroids.9 DDT is a pesticide banned in the US in the early 1970s but persists in rivers, lakes, and soil. PCBs were used in manufacturing and other industries in the US until the late 1970s when they were banned. PCBs were released into the air, water, and land through sewers, smokestacks, storm water runoff, spills, and direct application to the environment. They continue to persist in rivers, lakes, and soil. Today, women are exposed to DDT and PCBs mostly through their diet.
Cadmium
The heavy metal cadmium has been implicated in the development and progression of fibroids. Women are exposed to cadmium mostly through cigarette smoking, drinking water, and diet. Dietary sources of cadmium include seafood (particularly shellfish), rice, and non-organic leafy green and root vegetables. Cadmium is a known endocrine-disrupting metal. It can bind to estrogen receptor alpha, increasing expression, and nongenomic signaling pathways such as mitogen-activated protein kinase (MAPK). Also, cadmium has known estrogenic effects on female reproductive organs.10 Studies linking fibroids and cadmium provide inconsistent results and the method of heavy metal testing appears to account for some of the differences. For example, a 2014 study of 473 women with fibroids compared to women without fibroids found an association between whole blood cadmium but not urinary levels of cadmium.11 It is significant that the link was made with blood cadmium and not urine because urinary cadmium is thought of as the best way to measure cadmium in the body.
Cadmium has a direct effect on fibroids. It has been shown to induce growth in estrogen-responsive human uterine fibroid and myometrial cells. A recent study showed low levels of cadmium could induce cell proliferation in estrogen-responsive uterine fibroid cells.12 It also found the mechanism of action was through activation of the MAPK pathway rather than through direct interactions with estrogen receptor α and estrogen receptor β. As more studies are being done linking EDCs to uterine fibroids, the mechanism of action is becoming clear.
Summary
Endocrine-disrupting compounds are common in our environment. They are present in our air, water, food, plastics, cleaning products, cosmetic and grooming products, and other household items. Common EDCs include bisphenol-A, phthalates, persistent organic pollutants, and heavy metals such as cadmium. These toxins exert a hormone-disrupting effect, contributing to or exacerbating women’s health conditions. Uterine fibroids are a common estrogen-driven condition that is linked to many of these compounds. It is important for both patients and practitioners to know the sources of exposure to these toxins in order to avoid them and prevent the development of fibroids and other hormonal health conditions.
This article was first published in Townsend Letter, April 2017.
References
1. Beckmann CRB, et al. Obstetrics and Gynecology. 7th edition. Baltimore MD: Lippincott Williams and Wilklns; 2014.
2. Callahan TL, Caughey AB. Blueprints Obstetrics and Gynecology. 6th edition. Baltimore MD: Lippincott Williams and Wilkins; 2013.
3. Pollack AZ, et al. Bisphenol A, benzophenone-type ultraviolet filters, and phthalates in relation to uterine leiomyoma. Environ Res. 2015; 137:101-7.
4. Shen Y, et al. An evidence in vitro for the influence of bisphenol A on uterine leiomyoma. Eur J Obstet Gynecol Reprod Biol. 2014; 178:80-3.
5. Jeong EH, et al. The Relationship between Uterine Myoma Growth and the Endocrine Disruptor in Postmenopausal Women. J Menopausal Med. 2013; 19(3):130-4.
6. Kim YA, et al. Increased Urinary Phthalate Levels in Women with Uterine Leiomyoma: A CaseControl Study. See comment in PubMed Commons below/nt J Environ Res Public Health. 2016; 13(12):1247.
7. Sun J, et ai. Phthalate monoesters in association with uterine leiomyomata in Shanghai. Int J Environ Health Res. 2016; 26(3):306-16.
8. Weuve J, et al. Association of exposure to phthalates with endometriosis and uterine leiomyomata: findings from NHANES, 1999-2004. Environ Health Perspect. 2010; 118(6):825-32.
9. Trabert B, et al. Persistent organic pollutants (POPs) and fibroids: results from the ENDO study. J Expo Sei Environ Epidemiol. 2015; 25(3):278-85.
10. Pollack AK, et al. Cadmium and Reproductive Health in Women: A Systematic Review of the Epidemiologic Evidence. Curr Environ Health Rep. 2014; 1(2):172-184.
11. Johnstone EB, et al. Increased urinary cobalt and whole blood concentrations of cadmium and lead in women with uterine leiomyomata: Findings from the ENDO Study. Reprod Toxicol. 2014; 49:2732.
12. Gao X, et al. Cadmium and proliferation in human uterine leiomyoma cells: evidence of a role for EGFR/MAPK pathways but not classical estrogen receptor pathways. Environ Health Perspect. 2015; 123{4):331-6.
Published October 21, 2023
About the Author
Marianne Marchese, ND, is the author of 8 Weeks to Women’s Wellness. She graduated from the National University of Natural Medicine in 2002. Dr. Marchese maintains private practice in Phoenix, Arizona, and currently teaches gynecology and environmental medicine at Sonoran University of Health Sciences in Tempe, AZ. She has also been adjunct faculty at Southwest College of Naturopathic Medicine and Bastyr University. Dr. Marchese was named in Phoenix Magazine’s Top Doctor Issue as one of the top naturopathic physicians in Phoenix several years running. She lectures on topics related to women’s health and environmental medicine throughout the US and Canada; www.drmarchese.com