Pyrethroids,Phthalates Exposure And Risk Of Primary Ovarian Insufficiency In Chinese Women

With the environmental detection rate and environmental residues of Endocrine Disrupting Chemicals(EDCs)increasing year by year,the threat of EDCs to ecology and human health has attracted more and more attention from all over the world.Among EDCs,pyrethroids are a class of widely used insecticides,and phthalates are heavily used as plasticizers and softeners.These two types of chemicals are widely found in human settlements,leading to continued exposure.Female animal studies suggested that pyrethroid and/or phthalates exposure impaired ovarian function,which resulted in similar symptoms of primary ovarian insufficiency(POI).However,it is still unknown whether this association applies to women.(1)In this case-control study,a total of 172 POI patients and 247 control women were recruited in Zhejiang,China.The urinary concentrations of metabolites of pyrethroids,3-phenoxybenzoic acid(3-PBA)and 4-fluoro-3-phenoxybenzoic acid(4-F-3-PBA),as well as the serum concentrations of follicle-stimulating hormone(FSH),luteinizing hormone(LH)and anti-Mullerian hormone(AMH)were determined.The geometric mean of urinary 3-PBA in cases was 0.372 ?g/L(0.535 ?g/g creatinine),which was significantly higher than that in controls(0.251 ?g/L,0.390 gg/g creatinine).The associations of pyrethroid metabolites with POI and POI-related hormones were accessed using unconditional logistic regression.Higher urinary levels of 3-PBA were significantly associated with increased risk of POI[adjusted odds ratio(OR)=2.344,95%CI:1.193-4.607 for the highest vs.lowest quartile of 3-PBA,p=0.013].Stratified analyses showed that each log increase in urinary 3-PBA concentration was significantly associated with an 51.0%induction in odds of being in the highest quartile of FSH and 28.6%being in the highest quartile of LH levels,while a 25.9%reduction in odds of being in the highest quartile of AMH levels(All p for trend<0.05).To our knowledge,this is the first case-control study to report an association of pyrethroid exposure with increased risk of POI in women.(2)In this case-control study,the associations between phthalate exposure and POI in women were assessed.A total of 216 POI cases and 254 control women were recruited in Zhejiang,China.The urinary concentrations of 8 phthalate metabolites and the serum levels of ovarian-related hormones were determined.mono-isobutyl phthalate(MiBP)was the compound with the highest mean concentration of 61.4 ?g/g of creatinine.The mean concentrations of mono-methyl phthalate(MMP),mono-ethyl phthalate(MEP),MiBP,mono-n-butyl phthalate(MnBP)and the sum of 8 phthalate metabolites in cases were higher than those of controls,with a nonsignificant trend.Higher urinary concentrations of MiBP were significantly associated with increased risk of POI(OR=1.3 79,95%CI:0.728-2.613 for the fourth quartile;p for trend=0.013).The serum levels of estradiol(E2)were significantly negatively associated with the urinary concentrations of several phthalate metabolites.In addition,follicle stimulating hormone,a well-established marker of ovarian reserve,were significantly positively associated with the urinary concentrations of most phthalate metabolites in control women.To the best of our knowledge,this work for the first time reported the association of exposure to some phthalates with the risk of POI in women.