The association between exposure to multiple toxic metals and the risk of endometriosis: Evidence from the results of blood and follicular fluid

Background: Endometriosis affects up to 10 % of women of reproductive age and can lead to infertility. Research investigating whether combined exposure to arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg) is related to an increased risk of endometriosis, especially using different biological samples to validate the association, is very limited. Objective: This investigation aimed to evaluate the associations between the concentrations of As, Cd, Pb and Hg in blood and follicular fluid and the risk of endometriosis.Methods: A total of 609 endometriosis cases and controls seen at the reproductive center of the First Affiliated Hospital of Anhui Medical University in Hefei, China, between April 2020 and December 2021 were included in our study. Blood (217 cases and 234 controls) and follicular fluid (182 cases and 203 controls) samples were collected from these subjects. The concentrations of Cd, Hg, As and Pb in the blood and follicular fluid were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Unconditional logistic regression models were used to assess the associations between Cd, Hg, As or Pb levels and the risk of endometriosis; Bayesian kernel machine regression (BKMR) was used to evaluate the combined effect of metals on the risk of endometriosis.Results: We found significant associations between blood concentrations of As (highest vs. lowest tertile: aOR = 5.53, 95 % CI: 2.97, 10.30), Cd (second vs. lowest tertile: aOR = 1.96, 95 % CI: 1.07, 3.58; highest vs. lowest tertile: aOR = 3.21, 95 % CI: 1.79, 5.77), Pb (highest vs. lowest tertile: aOR = 2.73, 95 % CI: 1.56, 4.78) and Hg (high-level group vs. low-level group: aOR = 13.10, 95 % CI: 6.74, 25.44; second vs. lowest tertile: aOR = 15.27, 95 % CI: 4.96, 46.97; highest vs. lowest tertile: aOR = 35.66, 95 % CI: 11.99, 106.08) and increased risk of endometriosis adjusting for confounders. Follicular fluid As (highest vs. lowest tertile: aOR = 2.42, 95 % CI: 1.35, 4.33), Hg (highest vs. lowest tertile: aOR = 1.86, 95 % CI: 1.05, 3.29), Cd (second vs. lowest tertile: aOR = 2.45, 95 % CI: 1.29, 4.65; highest vs. lowest tertile: aOR = 3.12, 95 % CI: 1.67, 5.83), and Pb (second vs. lowest tertile: aOR = 1.97, 95 % CI: 1.11, 3.52) concentrations were positively associated with endometriosis risk. The BKMR analyses showed linear associations between the metal mixtures and the risk of endometriosis. Both in blood and in follicular fluid, As exhibited the highest contribution.Conclusion: The data from this study suggest that toxic metals, individually and as a mixture, play a role in the risk of endometriosis, thus providing a novel idea for endometriosis prevention.