Polyfluoroalkyl Chemicals and Menopause among Women 20–65 Years of Age (NHANES)

Office of Health Assessment and Translation, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA
Environmental Health Perspectives (Impact Factor: 7.98). 11/2013; 122(2). DOI: 10.1289/ehp.1306707
Source: PubMed


Polyfluoroalkyl chemicals (PFCs) such as perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) have been associated with early menopause. However, previous cross sectional studies have lacked adequate data to investigate possible reverse causality, i.e., higher serum concentrations due to decreased excretion after menopause.
We investigate the association between PFOS, PFOA, perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) and age at natural menopause among women ages 20-65 in NHANES.
We used proportional hazard models to estimate hazard ratios (HR) for the onset of natural menopause as a function of age and serum PFC levels, and to investigate reverse causation by estimating associations between PFC levels and rate of hysterectomy. We also used multivariable linear regression to determine whether time since menopause predicted serum PFC levels.
After adjusting for age at survey, race/ethnicity, education, ever smoking, and parity, women with higher levels of PFCs had earlier menopause compared to women with the lowest levels. We observed a monotonic association with PFHxS: the HR was 1.42 (95% CI: 1.08, 1.87) for serum concentrations in the 2(nd) vs. 1(st) tertile, and 1.70 (95% CI: 1.36, 2.12) for the 3(rd) vs. 1(st) tertile. We also found evidence of reverse causation: PFCs were positively associated with rate of hysterectomy, and time since natural menopause was positively associated with serum PFCs.
Our findings suggest a positive association between PFCs and menopause; however, at least part of the association may be due to reverse causation. Regardless of underlying cause, women appear to have higher PFC concentrations after menopause.

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    • "A large number of studies have reported on the presence of multiple compounds in human body fluids (Calafat et al. 2007; NHANES 2013), clearly showing that they are taken up by the body through various routes. Also, epidemiological studies have shown strong associations between compound mixtures and diseases , for instance in relation to human reproduction (Krysiak-Baltyn et al. 2012; Taylor et al. 2014). Therefore, since animal studies have shown effects of human relevant mixtures of environmental compounds given at doses close to No Observed Adverse Effect Levels (NOAELs) for single compounds (Christiansen et al. 2008, 2012; Axelstad et al. 2014), the presence of many of these chemicals simultaneously is of real concern to human health. "
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    ABSTRACT: Humans are constantly exposed to a significant number of compounds and many are readily detected in human body fluids. Worryingly, several of these compounds are either suspected to be, or have already been shown to be harmful to humans either individually or in combination. However, the potential consequences of low-dose exposure to complex mixtures remain poorly understood. We have profiled the effects on rat blood plasma and liver homeostasis using metabolomics and transcriptomics following 2-week exposure to either a mixture of 14 common chemicals (Mix), perfluorononanoic acid (PFNA) at low (0.0125 mg/kg/day) or mid (0.25 mg/kg/day) doses, or a combination of Mix and PFNA. In blood plasma, 63 and 64 metabolites were significantly changed upon exposure to Mix alone or PFNA ? Mix, respectively. Twelve of the metabolites were identified and comprised mainly lipids, with various lipid classes differentially affected across study groups. In the liver, expression of 182 and 203 genes—mainly related to energy homeostasis and lipid metabolism—were differentially expressed upon exposure to PFNA alone or PFNA ? Mix, respectively. In general, Mix alone affected lipid metabolism evident in blood plasma, whereas effects on lipid metabolism in the liver were mainly driven by PFNA. This study verifies that a chemical mixture given at high-end human exposure levels can affect lipid homeostasis and that the combined use of metabolomics and transcriptomics can provide complimentary information allowing for a detailed analysis of affected signaling pathways.
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    • "It has been found that occupational exposure to PFOS and PFOA is associated with an elevated cancer (such as bladder and colorectal cancer) morbidity rate (Alexander et al. 2003; Innes et al. 2014). Epidemiological investigations in the general population have revealed that elevated concentrations of serum PFOS and PFOA are associated with thyroid disease, atopic diseases, low birth weight, menopause, impairment of semen quality, as well as an increased prevalence of attentiondeficit hyperactivity disorder and infectious diseases in children (Apelberg et al. 2007; Darrow et al. 2013; Dong et al. 2013; Humblet et al. 2014; Taylor et al. 2014; Vested et al. 2013; Hoffman et al. 2010; Okada et al. 2012). Furthermore, one recent investigation has provided a profile of PFOS immunotoxicity, showing effects at levels 14-fold lower than the average blood concentrations of occupationally exposed humans and in the upper range of concentrations reported for the general population (Peden-Adams et al. 2008). "
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    ABSTRACT: Perfluorinated compounds (PFCs), such as perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), are a family of commonly used industrial chemicals whose persistence and ubiquity in blood samples of humans and wildlife have become a growing concern. Despite PFOS and PFOA having been found in human blood and tissue samples from occupationally exposed workers and the general worldwide population, little systematic knowledge has accrued with respect to exposure levels in Uyghurs in the Sinkiang-Uighur Autonomous Region of China, which is predominantly agricultural and pastoral. Our goal was to provide background data for biological monitoring in the general population of this region. In this study, 110 self-reported healthy human serum samples were collected from nonoccupationally exposed Uyghurs volunteers and analyzed by microbore HPLC-electrospray tandem mass spectrometry. Among the 110 blood specimens, PFOS was detected in 102 samples (93 %) and ranged from the lower limit of quantification of 0.01 to 22.63 μg/L with a median of 1.93 μg/L (interquartile range 1.00-3.43 μg/L). The median was higher among males (2.39 μg/L; interquartile range 1.23-4.40 μg/L) than that among females (1.20 μg/L; interquartile range 0.83-2.77 μg/L). No significant difference was observed with respect to age. The concentration of PFOA was lower than that of PFOS and was found only in seven samples (6 %) at concentrations above the limit of quantification. This study is the first investigation to reveal serum PFOS and PFOA levels in the general population of Uyghurs. PFOS and PFOA concentrations found in the present investigation were lower than those found in recent studies consisting of subjects from different geographic locations (PFOS 5.0-44.7 μg/L, PFOA 1.5-10 μg/L).
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