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Urinary metals and metal mixtures in midlife women: The Study of Women's Health Across the Nation (SWAN).

ABSTRACT: BACKGROUND:Little is known about the extent of exposure to metals and metal mixtures among midlife women. OBJECTIVES:We assessed exposure to multiple metals in the Study of Women's Health Across the Nation (SWAN), a multi-site, multi-racial/ethnic cohort of women at midlife. METHODS:We measured urinary concentrations of 21 metals (arsenic, barium, beryllium, cadmium, cobalt, chromium, cesium, copper, mercury, manganese, molybdenum, nickel, lead, platinum, antimony, tin, thallium, uranium, vanadium, tungsten and zinc) using high-resolution inductively coupled plasma-mass spectrometry among 1335 white, black, Chinese and Japanese women aged 45-56?years?at the third SWAN annual visit (1999-2000). Least squared geometric mean concentrations were compared across race/ethnicity, education, financial hardship, smoking, secondhand smoking, seafood intake and rice intake groups. Overall exposure patterns of multiple metals were derived using k-means clustering method. RESULTS:The percentage of women with detectable concentrations of metals ranged from 100% for arsenic, cesium, molybdenum and zinc, to less than 5% for platinum; 15 metals had detection rates of 70% or more. Asian women, both Chinese and Japanese, had higher urinary concentrations of arsenic, cadmium, copper, mercury, molybdenum, lead and thallium, compared with other race/ethnic groups, independent of sociodemographic, lifestyle, dietary, and geographic characteristics. Seafood and rice intake were important determinants of urinary arsenic, cesium, mercury, molybdenum and lead levels. Two distinct overall exposure patterns- "high" vs. "low" -- were identified. Women in the "high" overall exposure pattern were more likely to be Asians, current smokers, and to report high consumption of seafood and rice. Black women were less likely to have the high exposure pattern. CONCLUSIONS:Metal exposure of midlife women differs by racial/ethnic, sociodemographic, lifestyle, dietary, and geographic characteristics. Asian women may be experiencing the highest exposures to multiple metals compared with other racial/ethnic groups in the United States.

SUBMITTER: Wang X

PROVIDER: S-EPMC6583796 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Urinary metals and metal mixtures in midlife women: The Study of Women's Health Across the Nation (SWAN).

Wang Xin X Mukherjee Bhramar B Batterman Stuart S Harlow Siobán D SD Park Sung Kyun SK

International journal of hygiene and environmental health 20190515 5

<h4>Background</h4>Little is known about the extent of exposure to metals and metal mixtures among midlife women.<h4>Objectives</h4>We assessed exposure to multiple metals in the Study of Women's Health Across the Nation (SWAN), a multi-site, multi-racial/ethnic cohort of women at midlife.<h4>Methods</h4>We measured urinary concentrations of 21 metals (arsenic, barium, beryllium, cadmium, cobalt, chromium, cesium, copper, mercury, manganese, molybdenum, nickel, lead, platinum, antimony, tin, tha ...[more]

PMID: 31103473

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Project description:BackgroundEpidemiologic studies on associations between metals and insulin resistance and β-cell dysfunction have been cross-sectional and focused on individual metals.ObjectiveWe assessed the association of exposure to metal mixtures, based on assessment of 15 urinary metals, with both baseline levels and longitudinal changes in homeostatic model assessments for insulin resistance (HOMA-IR) and β-cell function (HOMA-β).MethodsWe examined 1262 women, aged 45-56 years at baseline (1999-2000), who were followed through 2015-2016, from the Study of Women's Health Across the Nation. Urinary concentrations of 15 metals (arsenic, barium, cadmium, cobalt, cesium, copper, mercury, manganese, molybdenum, nickel, lead, antimony, tin, thallium, and zinc) were determined at baseline. HOMA-IR and HOMA-β were repeatedly measured over 16 years of follow-up. A two-stage modeling was used to account for correlations in dependent and independent variables: In stage-1, linear mixed effects models were used to estimate the participant-specific baseline HOMA levels from random intercepts and participant-specific rates of changes from random slopes. In stage-2, adaptive elastic-net (AENET) models were fit to identify components of metal mixtures associated with participant-specific baseline levels and rates of changes in HOMA-IR and HOMA-β, respectively. An environmental risk score (ERS) was used to integrate metal mixture effects from AENET results.ResultsIn multivariable adjusted AENET models, urinary zinc was associated with higher HOMA-IR at baseline, whereas molybdenum was associated with lower HOMA-IR at baseline. The estimated changes in baseline HOMA-IR for one standard deviation increase in log-transformed urinary metal concentrations were 5.76% (3.05%, 8.55%) for zinc and -3.25% (-5.45%, -1.00%) for molybdenum, respectively. Urinary zinc was also associated with lower HOMA- β at baseline. Arsenic was associated with a slightly faster rate of decline in HOMA-β in the AENET model evaluating associations between metals and rate of changes. Significant associations of ERS with both HOMA-IR and HOMA-β at baseline were observed. ERS for the rate of changes was not calculated and examined in relation to rates of changes in HOMA-IR and HOMA-β because only a single metal was selected by AENET.ConclusionExposure to metal mixtures may be exerting effects on insulin resistance and β-cell dysfunction, which might be mechanisms by which metal exposures lead to elevated diabetes risks.

Project description:Adipokines, cytokines secreted by adipose tissue, may contribute to obesity-related metabolic disease. The role of environmental phenols and parabens in racial difference in metabolic disease burden has been suggested, but there is limited evidence. We examined the cross-sectional associations of urinary phenols and parabens with adipokines and effect modification by race. Urinary concentrations of 6 phenols (bisphenol-A, bisphenol-F, 2,4-diclorophenol, 2,5-diclorophenol, triclosan, benzophenone-3) and 4 parabens (methyl-paraben, ethyl-paraben, propyl-paraben, butyl-paraben) were measured in 2002-2003 among 1200 women (mean age = 52.6) enrolled in the Study of Women's Health Across the Nation Multi-Pollutant Study. Serum adipokines included adiponectin, high molecular weight (HMW)-adiponectin, leptin, soluble leptin receptor (sOB-R). Linear regression models were used to estimate the adjusted percentage change in adipokines per inter-quantile range (IQR) increase in standardized and log-transformed levels of individual urinary phenols and parabens. Bayesian kernel machine regression (BKMR) was used to evaluate the joint effect of urinary phenols and parabens as mixtures. Participants included white (52.5%), black (19.3%), and Asian (28.1%) women. Urinary 2,4-dichlorophenol was associated with 6.02% (95% CI: 1.20%, 10.83%) higher HMW-adiponectin and urinary bisphenol-F was associated with 2.60% (0.48%, 4.71%) higher sOB-R. Urinary methyl-paraben was associated with lower leptin in all women but this association differed by race: 8.58% (-13.99%, -3.18%) lower leptin in white women but 11.68% (3.52%, 19.84%) higher leptin in black women (P interaction = 0.001). No significant associations were observed in Asian women. Additionally, we observed a significant positive overall effect of urinary phenols and parabens mixtures in relation to leptin levels in black, but not in white or Asian women. Urinary bisphenol-F, 2,4-dichlorophenol and methyl-paraben may be associated with favorable profiles of adipokines, but methyl-paraben, widely used in hair and personal care products, was associated with unfavorable leptin levels in black women. Future studies are needed to confirm this racial difference.

Project description:Aims/hypothesisDiabetogenic effects of per- and polyfluoroalkyl substances (PFAS) have been suggested. However, evidence based on prospective cohort studies is limited. We examined the association between serum PFAS concentrations and incident diabetes in the Study of Women's Health Across the Nation Multi-Pollutant Study (SWAN-MPS).MethodsWe included 1237 diabetes-free women aged 45-56 years at baseline (1999-2000) who were followed up to 2017. At each follow-up visit, women with incident diabetes were identified by the presence of one or more of the following conditions: (1) use of a glucose-lowering medication at any visit; (2) fasting glucose ≥7 mmol/l on two consecutive visits while not on steroids; and (3) any two visits with self-reported diabetes and at least one visit with fasting blood glucose ≥7 mmol/l. Serum concentrations of 11 PFAS were quantified by online solid-phase extraction-HPLC-isotope dilution-tandem MS. Seven PFAS with high detection rates (>96%) (n-perfluorooctanoic acid [n-PFOA], perfluorononanoic acid [PFNA], perfluorohexane sulfonic acid [PFHxS], n-perfluorooctane sulfonic acid [n-PFOS], sum of perfluoromethylheptane sulfonic acid isomers [Sm-PFOS], 2-[N-methyl-perfluorooctane sulfonamido] acetic acid [MeFOSAA] and 2-[N-ethyl-perfluorooctane sulfonamido] acetic acid) were included in data analysis. Cox proportional hazards models were used to compute HRs and 95% CIs. Quantile-based g-computation was used to evaluate the joint effects of PFAS mixtures.ResultsAfter adjustment for race/ethnicity, site, education, smoking status, alcohol consumption, total energy intake, physical activity, menopausal status and BMI, the HR (95% CI) comparing the lowest with the highest tertile was 1.67 (1.21, 2.31) for n-PFOA (ptrend = 0.001), 1.58 (1.13, 2.21) for PFHxS (ptrend = 0.003), 1.36 (0.97, 1.90) for Sm-PFOS (ptrend = 0.05), 1.85 (1.28, 2.67) for MeFOSAA (ptrend = 0.0004) and 1.64 (1.17, 2.31) for the sum of four common PFAS (n-PFOA, PFNA, PFHxS and total PFOS) (ptrend = 0.002). Exposure to seven PFAS as mixtures was associated with an HR of 2.62 (95% CI 1.12, 6.20), comparing the top with the bottom tertiles for all seven PFAS.Conclusions/interpretationThis study suggests that PFAS may increase diabetes risk in midlife women. Reduced exposure to these 'forever and everywhere chemicals' may be an important preventative approach to lowering population-wide diabetes risk.

Project description:Obesity is a major threat to health, but the etiology of obesity is incompletely understood. Phthalates, synthetic chemicals ubiquitous in the environment, are suspected to have obesogenic effects, but the relationship of phthalates and obesity in humans remains uncertain. We examined whether phthalate exposure was associated with body fat gain in midlife women. We analyzed data from 1369 women in the Study of Women's Health Across the Nation Multi-Pollutant Study. Eleven phthalate metabolites measured in spot urine samples at baseline (1999/2000) were standardized with covariate-adjusted creatinine. Body weight (BW), fat mass (FM) from dual-energy X-ray absorptiometry (DXA), and body fat percentage (BF%) from DXA were measured near-annually until 2016/2017. For each metabolite, linear mixed effects models with time and log2(metabolite) interactions were examined, adjusting for demographic, lifestyle, and menopause-related factors. Analyses were conducted overall and stratified by baseline obesity status. As sensitivity analyses, all analyses were repeated using a second set of metabolites measured in 2002/2003. Higher levels of all metabolites except mono-carboxy-isononyl phthalate were associated with faster increases in BF%. Per doubling of metabolite concentrations, differences in five-year BF% change ranged from 0.03 percentage point (ppt) (95% confidence interval (CI): -0.03, 0.09) for mono-isobutyl phthalate to 0.09 ppt (95% CI: 0.02, 0.16) for mono(3-carboxypropyl) phthalate. Results were similar for FM change, but associations with BW change were mostly null. In stratified analyses by baseline obesity status, positive associations were strongest in women who were normal/underweight at baseline. When metabolites from 2002/2003 were used as exposures, most associations were attenuated and not statistically significant, but they remained positive for normal/underweight women. In conclusion, phthalate metabolites were associated with more rapid body fat gain in midlife women, but our results need confirmation given attenuation of estimates in the sensitivity analyses.

Dataset Information

Urinary metals and metal mixtures in midlife women: The Study of Women's Health Across the Nation (SWAN).

Publications

Urinary metals and metal mixtures in midlife women: The Study of Women's Health Across the Nation (SWAN).

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