Phthalate exposure increases uterine fibroid growth

Exposure to environmental phthalates was causally associated with uterine fibroid growth, according to data published in the Proceedings of the National Academy of Sciences.

“These toxic pollutants are everywhere, including food packaging, hair and makeup products and more, and their usage is not banned,” Serdar E. Bulun, MD, chair of the department of OB/GYN at Northwestern University Feinberg School of Medicine, said in a press release. “These are more than simply environmental pollutants. They can cause specific harm to human tissues.”

Bulun and colleagues analyzed data on urinary metabolite concentrations of phthalates reported in the Midlife Women’s Health Study, which was a prospective cohort study of 780 pre- and perimenopausal women living in the Baltimore area. The researchers assessed these data to determine associations between metabolites and diagnoses of uterine leiomyoma.

The researchers also collected uterine leiomyoma and uterine myometrium tissue from 48 premenopausal women undergoing myomectomy or hysterectomy. They used tissue samples from five to eight women in each of their experiments, which included assays of cell viability, cytotoxicity and apoptosis related to phthalate exposure.

Mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), which is a major metabolite of di-(2-ethylhexyl) phthalate (DEHP), had the strongest association with diagnosis of uterine leiomyoma, and had the strongest effects on cell viability and apoptosis.

Bulun and colleagues found that MEHHP increases cellular tryptophan uptake and kynurenine production and activates the aryl hydrocarbon receptor pathway. These mechanisms promoted the survival and growth of leiomyoma cells.

Notably, the dose-response effect of phthalate metabolites on leiomyoma was not linear but U-shaped, with the greatest effects observed with medium-range doses of metabolites.

“These findings are expected to open new avenues in the uterine leiomyoma research field and facilitate the development of novel strategies for the treatment or prevention of the disease,” Bulun and colleagues wrote.

References:

• Iizuka T, et al. Proc Natl Acad Sci U S A. 2022;doi:10.1073/pnas.2208886119.
• Uterine fibroid growth activated by chemicals found in everyday products. https://news.northwestern.edu/stories/2022/11/uterine-fibroid-growth-activated-by-chemicals-found-in-everyday-products/?fj=1. Published Nov. 14, 2022. Accessed Nov. 22, 2022.
• Ziv-Gal A, et al. Womens Midlife Health. 2017;doi:10.1186/s40695-017-0024-8.