Associations Between Exposure To Multiple Toxic Metals And Endometriosis In Women Of Reproductive Age

Background: Endometriosis(EMs)affects up to 10% of women of reproductive age and can cause symptoms such as menstrual cramps,pelvic pain and infertility.There has not been a unified understanding of the pathogenesis of EMs,which mainly includes anatomical,endocrine,genetic and other factors.In recent years,with the gradual deterioration of the environment,scholars have turned their perspectives to the association between environmental factors and the risk of EMs.Heavy metals are a major category of environmental pollutants that can cause great harm to human reproductive system.However,at present,the relevant studies on the combined exposure of heavy metals and the increased risk of EMs are still very limited,especially the use of different biological samples to verify this association.Objective: In this case-control study,four heavy metals were detected in the blood and follicular fluid of women of reproductive age who were being treated in vitro fertilisationembryo transfer(IVF-ET): Arsenic(As),Cadmium(Cd),Lead(Pb),and Mercury(Hg).Association between metal concentrations and the risk of EMs were also analyzed for individual and combined exposures.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: a OR = 5.53,95% CI: 2.97,10.30),Cd(second vs.lowest tertile: a OR = 1.96,95% CI: 1.07,3.58;highest vs.lowest tertile: a OR = 3.21,95% CI: 1.79,5.77),Pb(highest vs.lowest tertile: a OR = 2.73,95% CI: 1.56,4.78)and Hg(second vs.lowest tertile: a OR = 15.27,95% CI: 4.96,46.97;highest vs.lowest tertile: a OR = 35.66,95% CI: 11.99,106.08)and increased risk of endometriosis adjusting for confounders.Follicular fluid As(highest vs.lowest tertile: a OR = 2.42,95% CI: 1.35,4.33),Hg(highest vs.lowest tertile: a OR = 1.86,95% CI: 1.05,3.29),Cd(second vs.lowest tertile: a OR = 2.45,95% CI: 1.29,4.65;highest vs.lowest tertile: a OR = 3.12,95% CI: 1.67,5.83),and Pb(second vs.lowest tertile: a OR = 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 follicular fluid,the posterior inclusion probabilities(PIP)of As were 0.9944 and 0.9773,respectively,which showed that As exhibited the highest contribution in the joint exposure of toxic metals.Conclusion: The data from this study showed that single or combined exposure to toxic metals: As,Cd,Pb and Hg was positively associated with the risk of EMs,and the association was statistically significant.Which preliminarily confirm the theory of environmental factors in endometriosis.The specific pathogenesis remains to be further studied.The results of this paper can provide a new idea for the prevention and treatment of EMs in women of reproductive age.