Environmental Exposure to Emerging Alternatives of Per- and Polyfluoroalkyl Substances and Polycystic Ovarian Syndrome in Women Diagnosed with Infertility: A Mixture Analysis.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) have been previously linked to polycystic ovarian syndrome (PCOS), but only a few legacy PFAS were examined. OBJECTIVES: This study aimed to explore this association with a variety of PFAS, including legacy, branched-chain isomers, and emerging alternatives, as well as a PFAS mixture. METHODS: From 2014 to 2016, we conducted a multicenter, hospital-based case-control study on environmental endocrine disruptors and infertility in China. Three hundred sixty-six women with PCOS-related infertility and 577 control participants without PCOS were included in the current analysis. Twenty-three PFAS, including 3 emerging PFAS alternatives, 6 linear and branched PFAS isomers, 6 short-chain PFAS, and 8 legacy PFAS, were quantified in the plasma. Logistic regression and two multipollutant models [quantile-based g-computation (QGC) and Bayesian kernel machine regression (BKMR) methods] were used to assess the association of individual PFAS and PFAS mixture with PCOS, as well as the potential interactions among the congeners. RESULTS: After adjusting for potential confounders, Each 1-standard deviation higher difference in ln-transformed 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) and hexafluoropropylene oxide dimer acid (HFPO-DA) level was significantly associated with a 29% (95% CI: 1.11, 1.52) and 39% (95% CI:1.16, 1.68) higher odds of PCOS, respectively. Meanwhile, branched isomers of perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) (i.e., br-PFHxS, n-PFOS, 1m-PFOS, Σ3,4,5m-PFOS), short-chain PFAS (i.e., PFPeS and PFHxA) and other legacy PFAS [i.e., total concentrations of PFOS (T-PFOS), and perfluorododecanoic acid (PFDoA)] were significantly associated with increased odds of PCOS. The PFAS mixture was positively related to PCOS in the BKMR model. A similar trend was observed in QGC model, a ln-unit increase in the PFAS mixture was associated with a 20% increased risk of PCOS [adjusted odds ratio (aOR)=1.20 (95% CI: 1.06, 1.37)]. After controlling for other PFAS homologs, 6:2 Cl-PFESA, HFPO-DA, Σ3,4,5m-PFOS, and PFDoA were the major contributors based on the QGC and BKMR models. The associations were more pronounced in overweight/obese women. CONCLUSIONS: In this group of women, environmental exposure to a PFAS mixture was associated with an elevated odds of PCOS, with 6:2 Cl-PFESA, HFPO-DA, Σ3,4,5m-PFOS, and PFDoA being the major contributors, especially in overweight/obese women. https://doi.org/10.1289/EHP11814.

Exposure to bisphenol A and its analogs and polycystic ovarian syndrome in women of childbearing age: A multicenter case-control study.

BACKGROUND/OBJECTIVES: In recent years, the reproductive toxicity of new bisphenol analogs has garnered much interest, but it remains to be determined whether bisphenol analogs affect polycystic ovarian syndrome (PCOS). METHODS: This study utilized data from a multicenter hospital-based case-control study conducted in 2014-2016 to examine the association between endocrine-disrupting chemicals and infertility in China. 321 PCOS cases and 412 controls were included in the current analysis. We quantified seven bisphenol analogs in urine samples, including bisphenol A (BPA), bisphenol AP (BPAP), bisphenol AF (BPAF), bisphenol B (BPB), bisphenol S (BPS), bisphenol P (BPP), and bisphenol Z (BPZ). Spearman correlation and generalized linear regression were used in assessing the relationship between bisphenol analogs and hormonal parameters. To examine the association of bisphenol analogs with odds of PCOS, multiple logistic regression, and two multi-pollutant models [quantile-based g-computation (QGC) and extreme gradient boosting (XGBoost) methods] were used. RESULTS: After covariates adjustment, BPA, BPS, and BPAF were positively correlated with testosterone (T) in the control group (P < 0.05). Dose-response relationships were discovered between BPA, BPS, BPZ, and BPAF quartiles and PCOS. Mixed exposure to seven bisphenol analogs was found to be positively associated with the odds of PCOS (adjusted odds ratio = 1.26; 1.12-1.45), which was primarily driven by BPS (weight = 0.51), BPZ (weight = 0.26), and BPAF (weight = 0.23). Women who were overweight or obese tended to have a stronger association between bisphenol analogs and PCOS than normal-weight women. CONCLUSIONS: Environmental exposure to bisphenol analogs was associated with increased odds of PCOS in this case-control study. This association was stronger among obese and overweight women.

Marital status and survival in laryngeal squamous cell carcinoma patients: a multinomial propensity scores matched study.

OBJECTIVE: To explore the correlation between the marital status and prognosis of patients with laryngeal squamous cell carcinoma (LSCC). STUDY DESIGN: MPSM was adopted to minimize the maximum standardized average difference of the covariates among the four groups with different marital status. SETTING: Multinomial propensity scores matching (MPSM) based on data from the surveillance, epidemiology, and end results (SEER) database. METHODS: The Kaplan-Meier method and log-rank test were used to compare the survival outcomes of these groups with different marital status. RESULTS: Totally, 16,981 LSCC patients (median [IQR] age 62 [55-69] years; 829 [76.41%] males) from 2004 to 2016 were included in this study. Among them, 9112 (53.66%) were married, 2708 (15.95%) divorced or separated, 1709 (10.06%) widowed, and 3452 (20.33%) single. After MPSM, the weights make the characteristics of four groups with different marital status sufficient balance. The Kaplan-Meier method and log-rank test showed widowed patients may lead to the highest mortality rate while married patients have a higher survival rate than the other three groups. Single and divorced or separated patients had no significant difference in the survival rate. In addition, multivariate analysis by controlling for confounding factors showed that in male, well-differentiated, and early stage patients, compared with married, unmarried was an independent risk factor for CSS (P < 0.05). CONCLUSION: Marital status showed a significant association with the survival status of LSCC patients. Importantly, the outcome of married patients was better, while widowed patients tended to have worse prognosis.

Associations Between Dietary Inflammatory Index and Sex Hormones Among 6- to 19-Year-Old Children and Adolescents in NHANES 2015-2016.

Objectives: This study aimed to assess the relationship between dietary inflammatory index (DII) and sex steroids in children (6-11 years old) and adolescents (12-19 years old) in the U.S. National Health and Nutrition Examination Survey, 2015-2016. Methods: Participants between the ages of 6-19 have 24-hour dietary intake data, serum sex hormones [total testosterone (TT), estradiol (E2)], and sex hormone-binding globulin (SHBG) available data (n = 1382). The free androgen index (FAI) is calculated as TT divided by SHBG and the ratio of TT to E2 (TT/E2). The constructed puberty state is defined as high levels of steroid hormones (TT≥50 ng/dL in men, E2≥20 pg/ml in women) or onset of menarche. Multiple linear regression analysis was stratified by gender-age and gender-pubertal status groups to evaluate the association between DII and sex hormone levels. Results: After adjusting for covariates, the association between consecutive DII and sex hormone indicators by gender and age group. In male adolescents, DII was always negatively associated with TT (P-trend = 0.09), FAI (P-trend = 0.03) and E2 (P-trend = 0.01), and monotonically positively associated with SHBG (P-trend = 0.02).In female adolescents, with the increase of DII, a significant positive correlation with SHBG was observed (ß 0.017, 95%CI: 0.009,0.053) (Table 3). Among female adolescents, a significant negative association between DII and TT and a significant positive association between SHBG were observed in this group. Moreover, DII was positively associated with SHBG of prepubertal males and negatively associated with FAI of prepubertal females. Conclusions: DII was associated with decreased levels of certain sex steroid hormones (TT, FAI, and E2) and increased levels of SHBG in adolescents or pubertal individuals, with the associations presenting somewhat sex-dependent pattern. However, there is little evidence that there is a significant association in children or prepubertal children. Further research needs to be carried out to verify our results.