Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are persistent synthetic chemicals that are widely used in industrial applications and often detectable in humans. In rats, PFASs can interfere with the estrous cycle. In humans, menstruation has been viewed as a proxy of female fecundity, and periodic menstruation plays a critical role in endometrial sloughing in the absence of pregnancy and in preparing for embryo implantation. We investigated the association between PFAS exposure and menstrual cycle characteristics in women who plan to become pregnant. Plasma level of 10 PFASs was measured in 950 women who were attempting to become pregnant and recruited in two preconception care clinics in Shanghai, China, from August 2013 to April 2015. Information on menstrual cycle characteristics was collected by questionnaires. Associations between PFAS levels and menstrual cycle regularity, length, and bleeding volume were examined using multiple logistic regression models. Pre-pregnant women with higher levels of log-transformed perfluorooctanate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonate (PFHxS) had increased odds of self-reported history of irregular menstrual cycle [PFOA-adjusted odds ratio (OR)=1.52 (95% CI: 1.08, 2.15); PFOS OR=1.29 (95% CI: 0.98, 1.70); PFNA OR=1.50 (95% CI: 1.03, 2.07); PFHxS OR=1.80 (95% CI: 1.17, 2.77)] and long menstrual cycle [PFOA OR=1.50 (95% CI: 1.06, 2.10); PFOS OR=1.34 (95% CI: 1.02, 1.75); PFNA OR=1.49 (95% CI: 1.05, 2.11); PFHxS OR=1.73 (95% CI: 1.13, 2.65)]. Log-transformed PFOA, PFOS, PFNA. and PFHxS levels were negatively associated with self-reported history of menorrhagia [PFOA OR=0.37 (95% CI: 0.21, 0.65); PFOS OR=0.57 (95% CI: 0.37, 0.90); PFNA OR=0.47 (95% CI: 0.26, 0.86); PFHxS OR=0.14 (95% CI: 0.06, 0.36)]. Certain PFASs are associated with abnormal menstruation in humans. https://doi.org/10.1289/EHP1203.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been reported to disrupt endocrine system and reproduction. However, epidemiological evidence on the association between PFAS and preeclampsia is inconsistent. We aimed to investigate the association between prenatal PFAS exposure and hypertensive disorders of pregnancy (HDP) in humans. PFAS were measured by liquid chromatography system coupled with tandem mass spectrometry in 687 umbilical cord plasma samples collected between 2011 and 2012 in Shanghai, China. Information on HDP including gestational hypertension and preeclampsia was abstracted from medical records. Multiple logistic regression was used to examine the association of each PFAS with gestational hypertension, preeclampsia, and overall HDP in separate models. Elastic net regression with logit link was used to identify independent associations between exposures and outcomes. Logistic regression was used to obtain the unpenalized estimates of the selected PFAS components for the associations with outcomes, adjusting for age, education level, pre-pregnancy BMI, parity, and mutual adjustment of selected PFAS. The risk of gestational hypertension and preeclampsia was 3.3% and 2.8% in our subjects, respectively. Perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), perfluoroundecanoic acid (PFUA) were associated with preeclampsia based on elastic net penalty regression. In the fully adjusted statistical model, women with a higher level of standardized ln-transformed PFBS had an increased odds of preeclampsia [adjusted odds ratio (AOR): 1.81, 95% confidence interval (CI): 1.03–3.17], and overall HDP (AOR: 1.64, 95% CI: 1.09–2.47). Prenatal exposure to PFBS was positively associated with the risk of preeclampsia and overall HDP.

Humans are widely exposed to environmental perfluoroalkyl substances (PFAS), which may affect glucose homeostasis. However, research linking PFAS exposure to glucose homeostasis during pregnancy is limited and the results were inconsistent. We aimed to investigate the association between PFAS exposure and glucose homeostasis in pregnancy in a large prospective cohort. A total of 2747 pregnant women who participated in the Shanghai Birth Cohort, had blood samples in early pregnancy and completed a 75 g oral glucose tolerance test (OGTT) at 24-28 gestational weeks were included. 10 PFAS were determined by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS-MS) in the plasma samples in early pregnancy. Logistic regression was used to explore the associations between PFAS concentrations and gestational diabetes mellitus (GDM), while multiple linear regression was used to model the associations between PFAS and OGTT fasting, 1-h and 2-h glucose levels. Potential confounders were adjusted. Bayesian kernel machine regression (BKMR) and a quantile-based g-computation approach (qgcomp) were employed to explore the joint and independent effects of PFAS on glucose homeostasis. The incidence of GDM was 11.8%. One log-unit increment in plasma concentrations in early pregnancy was associated with an increased risk of GDM for perfluorobutane sulfonate (PFBS) (adjusted odd ratio (aOR) = 1.23, 95% confidence interval (95% CI): 1.05, 1.44) and perfluoroheptanoic acid (PFHpA) (aOR = 1.25, 95% CI: 1.07, 1.46). Perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexanesulfonate (PFHxS) and PFHpA were positively correlated with 1-h and 2-h glucose levels. Results of the mixed exposure model showed that the joint effects of PFAS were significantly associated with abnormal glucose homeostasis; In the BKMR model, PFAS mixture exposure was positively associated with the GDM incidence, 1-h and 2-h glucose levels and negatively correlated with FBG level. A similar trend could be observed in qgcomp and the positive correlation between PFAS and 2-h glucose level was significant (β = 0.12, 95% CI: 0.04, 0.20). PFOS, PFNA and PFHpA may be the main contributors after controlling for other PFAS congeners. PFOS was significantly correlated with GDM incidence and 2-h glucose level, and PFHpA was significantly associated with FBG and 2-h glucose levels. The above associations were more prominent among women with a normal prepregnant BMI. Environmental exposure to PFAS may affect glucose homeostasis in pregnancy and increase the risk of GDM, especially in normal weight women.

Organophosphate esters (OPEs) are increasingly used as flame retardants and plasticizers in various products. In vivo and in vitro studies suggest that OPEs can affect metabolic health but the human evidence is lacking. We analyzed data from the U.S. National Health and Nutrition Examination Survey, 2011-2014, to examine the associations between urinary OPE metabolites and metabolic syndrome (MetS) and its components in adults. We included a total of 1157 adults aged ≥20 years who had information on urinary OPE metabolites, components of MetS and essential covariates in the current analyses. MetS was composed of hyperglycemia, hypertension, hypertriglyceridemia, low high-density cholesterol, and central obesity. Binary logistic regression and weighted quantile sum (WQS) regression were used to assess the associations of individual OPE metabolites and OPEs mixture with MetS and its components. All analyses were conducted in men and women separately. Potential effect modification by age, serum total testosterone (TT) level and menopause status were also examined via stratified analyses as well as by testing the significance of the interaction term with exposure. After adjusting for confounders, bis(2-chloroethyl) phosphate (BCEP) and bis(1,3-dichloro-2-propyl) phosphate (BDCPP) were positively associated with MetS in a dose-dependent manner (P-trend = 0.02 and 0.02 for BCEP and BDCPP, respectively) in all men. Meanwhile, increasing quartiles of DPHP was positively associated with hyperglycemia (P-trend = 0.03), but DBUP was inversely associated with central obesity (P-trend = 0.02). WQS analyses in all men found that OPEs mixture (OPEs index) was positively associated with MetS [odds ratio (OR) for OPEs index: 1.65; 95%CI :1.21, 2.24], hyperglycemia (OR:1.47; 95%CI:1.09,2.00), and central obesity (OR:1.36; 95%CI:1.01,1.83). Although there was no significant interaction between exposure and effect modifiers, stratified analyses in men suggested that significant associations were mainly limited to those aged < 60 years or those with TT < 437 ng/dL (the median level in men). By contrast, the associations with MetS and its components were sparse and inconsistent in women except for the positive association between OPEs index and central obesity. In this cross-sectional study, exposure to OPEs was positively associated with elevated odds of MetS and individual components in men, especially among those aged <60 years or those with relatively low TT level. But the associations were less apparent in women except for the consistent positive association of OPEs mixture with central obesity. Nevertheless, these results need to be interpreted with caution and should be confirmed in future studies, ideally with multiple urine samples collected prospectively to improve the exposure measurement of OPEs.