全氟化合物暴露对美国12~20岁人群性激素水平的影响

Exposure to per-and polyfluoroalkyl substances in relation to serum sex hormones levels among American populations aged 12-20 years

[背景]全氟化合物(PFASs)是一类主要由人工合成的氟代有机化合物。现有研究表明PFASs具有内分泌干扰效应,会影响性激素的稳态,但青春期年龄段的流行病学研究较少。[目的]探讨12~20岁人群PFASs暴露与其血清性激素水平间的联系。[方法]本研究基于美国国家健康与营养调查(NHANES)的公开数据(2013—2016年),选取12~20岁人群中同时具有人口学信息、10种血清PFASs[包括直链PFOA(n-PFOA)、支链PFOA(Sb-PFOA)、直链PFOS(n-PFOS)、支链PFOS(Sm-PFOS)、全氟癸酸(PFDeA)、全氟己烷磺酸(PFHxS)、全氟壬酸(PFNA)、2-(N-甲基全氟辛烷磺酰胺基)乙酸(Me-PFOSA-AcOH)、全氟十一酸(PFUA)、全氟十二酸(PFDoA)]、3种性激素[包括雌二醇(E2)、睾酮(T)及性激素结合蛋白(SHBG)]数据的人群(n=682)。血清PFASs和性激素分别使用高效液相色谱质谱串联法,液相色谱质谱串联法和酶联免疫吸附法检测。分别按照性别、年龄和种族进行分层,运用多元线性回归模型分析PFASs暴露与性激素水平之间的关系。[结果]682例12~20岁研究对象中,男性359例(52.6%),平均年龄为(15.83±2.44)岁;女性323例(47.4%),平均年龄为(15.74±2.49)岁。5种PFASs(n-PFOS、n-PFOA、PFNA、PFHxS、Sm-PFOS)检出率均接近100%(99.7%~99.9%),其次为PFDeA(62.0%),其余4种PFASs均低于50%;10种PFASs中,n-PFOS质量浓度(下称浓度)中位数最高(2.20μg·L^-1),其次是n-PFOA(1.30μg·L^-1),其余PFASs浓度中位数范围为0.07~0.90μg·L^-1。调整混杂因素后发现,在男性中:n-PFOA浓度与E2浓度呈负相关(b=-0.13,95%CI:-0.26^-0.003);按年龄分层后,PFHxS在16~20岁组中与E2呈负相关(b=-0.09,95%CI:-0.17^-0.01),在12~15岁组中与SHBG呈负相关(b=-0.09,95%CI:-0.17^-0.004);在女性中:n-PFOA、PFHxS、Sm-PFOS与SHBG呈负相关(b=-0.18,95%CI:-0.29^-0.07;b=-0.09,95%CI:-0.16^-0.01;b=-0.12,95%CI:-0.22^-0.02);按年龄分层后,仅在16~20岁组中发现PFHxS与SHBG呈负相关(b=-0.11,95%CI:-0.21^-0.003),PFDeA与T呈正相关(b=0.12,95%CI:0.02~0.23)。[结论]某些PFASs暴露可引起青春期性激素水平的降低,表现为与男性E2水平呈负相关,与女性SHBG水平呈负相关,且在16~20岁年龄段效应显著。

[Background]Per-and polyfluoroalkyl substances(PFASs)are a class of artificially synthesized fluorinated organic compounds.Recent studies have found that PFASs have endocrine disrupting effects and can affect the homeostasis of sex hormones,but there are few relevant epidemiological studies on puberty.[Objective]This study is conducted to explore the associations between serum PFASs and serum sex hormones among adolescents aged 12 to 20 years.[Methods]This study was based on the public online data of the National Health and Nutrition Examination Survey(NHANES)(2013—2016).A subset(n=682)of populations aged 12-20 years that had data on demographic information,linear PFOA(n-PFOA),sum of branched isomers of PFOA(Sb-PFOA,branched PFOA isomers),linear PFOS,(n-PFOS),sum of PFOS isomers,(Sm-PFOS,monomethyl branched PFOS isomers),pefluorodecanoic acid(PFDeA),perfluorohexane sulfonic acid(PFHxS),perfluorononanoic acid(PFNA),2-(N-methyl-perfluoroctanesulfonamido)acetic acid(Me-PFOSA-AcOH),perfluoroundecanoic acid(PFUA),perfluorododecanoic acid(PFDoA),estradiol(E2),testosterone(T),and sex hormone binding globulin(SHBG)was used.Serum PFASs and sex hormones were measured using high performance liquid chromatography coupled with tandem mass spectrometry,liquid chromatography-tandem mass spectrometry,and enzyme-linked immunosorbent assay respectively.Associations between PFASs and sex hormones were assessed using multiple linear regression models stratified by sex,age,and race.[Results]Among the 628 participants aged 12-20 years,359 were males(52.6%)averaged(15.83±2.44)years old,and 323 were females(47.4%)averaged(15.74±2.49)years old.The detection rates of five PFASs(n-PFOS,n-PFOA,PFNA,PFHxS,and Sm-PFOS)approached 100%(99.7%-99.9%),followed by PFDeA(62.0%),and the other four PFASs were all below 50%.The median exposure level of n-PFOS was the highest(2.20μg·L^-1),followed by n-PFOA(1.30μg·L^-1),and the remaining PFASs varied from 0.07-0.90μg·L^-1.After adjustments for potential confounders,in males,exposure to n-PFOA was negatively associated with E2(b=-0.13,95%CI:-0.26--0.003);when stratified by age,PFHxS was negatively associated with E2(b=-0.09,95%CI:-0.17--0.01)in the group of 16 to 20 years old,and negatively associated with SHBG(b=-0.09,95%CI:-0.17--0.004)in the group of 12 to 15 years old.In females,n-PFOA(b=-0.18,95%CI:-0.29--0.07),PFHxS(b=-0.09,95%CI:-0.16--0.01),and Sm-PFOS(b=-0.12,95%CI:-0.22--0.02)were negatively associated with SHBG;when stratified by age,only in the group of 16 to 20 years old,PFHxS was negatively associated with SHBG(b=-0.11,95%CI:-0.21--0.003),and PFDeA was positively associated with T(b=0.12,95%CI:0.02-0.23).[Conclusion]Exposure to certain PFASs may be associated with decreased sex hormone levels in puberty,such as lower E2 in males and lower SHBG in females,and these effects are strongest in the 16-20 years age group.