Background

Although an alteration in sex hormones has been linked to perfluoroalkyl substances (PFAS) in premenopausal women and girls, whether such associations exist in postmenopausal women remains uncertain.

Objects

To examine the associations between serum PFAS concentrations and sex hormone levels in postmenopausal women.

Methods

Data from the National Health and Nutrition Examination Survey (NHANES) 2013–2016 waves were used. A total of 706 postmenopausal women with information on serum PFAS [perfluorohexane sulfonic acid (PFHxS), pefluorodecanoic acid (PFDA); perfluorononanoic acid (PFNA); linear perfluorooctanoate (n-PFOA); linear perfluorooctane sulfonate (n-PFOS); monomethyl branched isomers of PFOS (Sm-PFOS)], sex hormones indicators [e.g., total testosterone (TT), estradiol (E₂) and sex hormone binding globulin (SHBG)] as well as selected covariates were included. An indicator of circulating free testosterone (FT), and ratio of TT to E₂ (TT/E₂) were generated. Multiple linear regression accounting for the primary sampling unit, strata, and environmental sampling weights of PFAS was used for association analyses. Effect modification by obesity and type of menopause was explored via stratified analyses as well as the testing of interaction terms. Principal component analysis (PCA) and Bayesian kernel machine regression (BKMR) were conducted to assess these relationships in a multiple PFAS exposure setting.

Results

After adjusting for potential confounders, total perfluorooctanoate (TPFOA: n-PFOA + Sb-PFOA) and total perfluorooctane sulfonate (TPFOS: n-PFOS + Sm-PFOS), and their linear and branched isomers were positively associated with two androgen indicators (i.e., TT and FT). PCA results revealed that the principal component (PC) composed of n-PFOA was positively associated with ln (TT) [β = 0.09, 95% confidential interval (CI): 0.02, 0.16; per ln-ng/mL increase in exposure], and ln (FT) (β = 0.12, 95% CI: 0.05, 0.2) in overweight/obese [body mass index (BMI) ≥ 25 kg/m²] women, but not in those with BMI < 25 kg/m². Additionally, among overweight/obese women, PFHxS was positively associated with androgens and negatively with ln (SHBG) (β = -0.06, 95% CI: −0.12, −0.01). The PC composed of Sm-PFOS, n-PFOS, and PFHxS was positively associated with ln (TT) levels among overweight/obese women. Results from BKMR also confirmed the findings on n-PFOA and PFHxS.

Conclusions

Our study indicates that n-PFOA and PFHxS were positively associated with levels of several androgen indicators in postmenopausal women, particularly among overweight/obese ones. Given the higher risk of cardiometabolic diseases associated with elevated levels of androgens in postmenopausal women, future studies are needed to explore the potential underlying mechanisms.

中文翻译：

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绝经后妇女中的全氟烷基物质和性激素：NHANES 2013–2016

背景

尽管绝经前妇女和女孩的性激素改变与全氟烷基物质（PFAS）有关，但绝经后妇女是否存在这种关联尚不确定。

对象

要检查绝经后妇女血清PFAS浓度与性激素水平之间的关联。

方法

使用了2013-2016年美国国家卫生和营养检验调查（NHANES）的数据。共有706名绝经后妇女提供了有关血清PFAS [全氟己烷磺酸（PFHxS），全氟癸酸（PFDA）的信息；全氟壬酸（PFNA）; 线性全氟辛酸酯（n-PFOA）; 线性全氟辛烷磺酸盐（n-PFOS）; 包括PFOS的单甲基支链异构体（Sm-PFOS），性激素指标[例如总睾丸激素（TT），雌二醇（E ₂）和性激素结合球蛋白（SHBG）]以及所选的协变量。循环游离睾丸激素（FT）以及TT与E _2的比率（TT / E ₂）生成。关联分析使用考虑了PFAS的主要抽样单位，地层和环境抽样权重的多元线性回归。通过分层分析和交互作用项的测试，探讨了肥胖和更年期类型对效果的影响。进行了主成分分析（PCA）和贝叶斯核仁机器回归（BKMR），以评估在多个PFAS暴露环境下的这些关系。

结果

在调整了潜在的混杂因素后，总全氟辛酸酯（TPFOA：n-PFOA + Sb-PFOA）和总全氟辛烷磺酸（TPFOS：n-PFOS + Sm-PFOS）及其线性和支链异构体与两个雄激素指标正相关（即，TT和FT）。PCA结果显示，由n-PFOA组成的主要成分（PC）与ln（TT）呈正相关[β= 0.09，95％机密区间（CI）：0.02，0.16；超重/肥胖[体重指数（BMI）≥25 kg / m ² ]的女性，每ln-ng / mL暴露增加]和ln（FT）（β= 0.12，95％CI：0.05，0.2），但BMI <25 kg / m ^2的患者中不适用。此外，在超重/肥胖妇女中，PFHxS与雄激素呈正相关，与ln（SHBG）呈负相关（β= -0.06，95％CI：-0.12，-0.01）。由Sm-PFOS，n-PFOS和PFHxS组成的PC与超重/肥胖妇女的ln（TT）水平呈正相关。BKMR的结果也证实了有关n-PFOA和PFHxS的发现。

结论

我们的研究表明，n-PFOA和PFHxS与绝经后妇女，尤其是超重/肥胖妇女中几种雄激素指标的水平呈正相关。鉴于绝经后妇女中与雄激素水平升高相关的心血管代谢疾病的风险较高，需要进行进一步的研究以探讨潜在的潜在机制。