Environmental Toxicants and Uterine Leiomyoma in Patient and in-Vitro Studies: A Systematic Review

Study Objective Uterine leiomyoma, often called fibroids, are benign tumours in the uterus and are prevalent in up to 70% of women. Environmental toxicants that can mimic and disrupt estrogen signaling have led to the hypothesis that toxicants may be associated with increased prevalence of leiomyoma. Our objective was to systematically review the literature examining this association. Design A systematic search of MEDLINE, EMBASE, SCOPUS, and Web of Science was conducted (to October 2020) to identify primary literature reporting toxicant exposure on leiomyoma. Only human or human cell studies in English were included. Data extracted included type of exposure, dosage and effect size. Quality assessment was done using the Newcastle-Ottawa Scale. Setting N/A. Patients or Participants N/A. Interventions N/A. Measurements and Main Results Thirty-three studies (24 patient and 9 in-vitro) were included. Patient studies examined plasticizers (phthalates, n=9; others, n = 3), bisphenol A (n = 7), phenols (n=5), organohalogen compounds (n = 5), heavy metals (n = 3), polycyclic aromatic hydrocarbons (n=1), and hair relaxers (n=1). Positive associations were identified for each group of toxicants, though results were often conflicting. Specific compounds most commonly positively associated with fibroids were di (2- ethylhexyl) phthalate (DEHP) metabolites (phthalates; n=5); nonylphenol (phenols; n=5), and bisphenol A (n=4). The majority of in vitro studies (n=6) reported effects of bisphenol A on leiomyoma growth and half of these suggested mediation through the estrogen receptor alpha signaling pathway. Studies that measured toxicants in urine had more positive outcomes than studies examining the same toxicants in the serum. Conclusion Review of the literature supports environmental toxicants as potential contributors in leiomyoma prevalence. We found that DEHP, bisphenol A, and nonylphenol were often positively associated with leiomyoma. Additionally, we found differential outcomes based on the tissue which the exposure was drawn from. The cause-effect relationship of toxicant exposure on leiomyoma will be an imperative topic for future research.