Endocrine disrupting chemicals associated with uterine leiomyoma and endometriosis in US women

A study published in Frontiers in Endocrinology correlates US women’s multiple chemical exposures to uterine leiomyoma (UL) or uterine fibroids (UF) and endometriosis (EM).

Researchers in Nanjing, China, have found that exposure to multiple endocrine disruptors is associated with UL and EM. These conditions represent a major public health issue, and environmental causes have not been adequately examined, study authors said.

Yuqing Zhang, of the Department of Women Health Care at the Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital and colleagues examined the effects of endocrine disrupting chemicals such as phthalates, which can be found in plastic packaging for food and water, toys, building materials, and some cosmetics and personal care products.

“Among the chemicals, the exposure of endocrine-disrupting chemicals (EDCs) raised great concern as their potential disturbance on ovarian steroid hormone. The chemicals disrupting the balance of female hormones could play a role in the development of uterine leiomyomata and endometriosis,” the authors reported.

Zhang and colleagues looked at data from 1,204 women between the ages of 20-54 years who completed the National Health and Nutrition Examination Survey (NHANES) 2001-2006. NHANES used a multiple-layered probability sampling design that focused on a representative sample population located in counties across the US, according to the study report. The participants were evaluated for exposure to 10 common endocrine-disrupting chemicals: monobutyl phthalate (MBP), monoethyl phthalate (MEP), mono(2-ethylhexyl) phthalate (MEHP), monobenzyl phthalate (MBzP), mono(3-carboxypropyl) phthalate (MCPP), mono-isobutyl phthalate (MIBP), cadmium (Cd), lead (Pb), and mercury (Hg). Blood and urine were collected with mobile examination centers and were frozen before being evaluated.

Samples were examined with various chromatography methods depending on the chemical substance. High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was used for phthalate metabolites. High performance liquid chromatography–atmospheric pressure photoionization–tandem mass spectrometry was employed for equol. Inductively coupled plasma mass spectrometry was used for Pb and Cd levels, and cold vapor atomic absorption spectrophotometry was used to detect Hg.

Women answered questions about EM and UL. Researchers asked 2 questions based upon the diagnosis of either condition: 1. Has a doctor or other health care professional ever told you that you had endometriosis? 2. Has a doctor or other health care professional ever told you that you had uterine fibroids? Those with positive answers were classified as patients and they then were asked about their age at receiving the first diagnosis, according to the report.

Researchers then examined how detected chemicals were correlated with UL and EM with a multivariable logistic regression model, a weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models.

Researchers reported chemicals most strongly associated with UL in single chemical analysis included Hg (OR: 1.91, 95% CI: 1.14, 3.25) and equol (OR: 1.90, 95% CI: 1.11, 3.27). They said results with the WQS and BKMR models further confirmed the association between Hg, equol, and UL (OR: 2.54, 95% CI: 1.52, 4.29), and added that WQS and BKMR found a negative association between mono(2-ethylhexyl) phthalate (MEPH)and UL.

“Our study found a positive association between urinary equol levels and uterine leiomyomata, which hasn’t been reported before,” researchers said. EM was not associated with individual chemicals in tertile 3, according to the authors. However, EM had a marginally positive association in the WQS index (OR: 2.01, 95% CI: 0.98, 4.15), “and a significant positive association was identified in sub- analysis 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,” they reported.

The researchers reported several study limitations. Among these, they said that the NHANES study is designed cross-sectionally, and that disease was diagnosed years before chemical exposures were measured. They noted that changes in exposure levels following diagnosis could result in measurement bias. They also said when patients self-report UL and EM, cases may be missing due to a lack of symptoms. They also added that the effects of other endocrine disruptors such as pesticides, phenols, and polychlorobiphenyls were not included in the study due to a lack of exposure data.

The authors emphasized that the study provides evidence that endocrine-related chemical mixtures do have an effect on the female reproductive system, and that more research is needed to discover the ways in which chemical endocrine disruptors cause these effects.

Reference

Zhang Y, Lu Y, Ma H, Xu Q, Wu X. Combined exposure to multiple endocrine disruptors and uterine leiomyomata and endometriosis in US women. Front Endocrinol (Lausanne). 2021;12:726876. Published 2021 Aug 20. doi:10.3389/fendo.2021.726876