Polychlorinated biphenyls and incident coronary heart disease-related outcomes in Great Lakes fish consumers.

BACKGROUND: Exposure to polychlorinated biphenyls (PCBs) has been linked to risk factors for cardiovascular disease such as increased inflammation, accelerated atherosclerosis, diabetes, and sex hormone dysregulation. Furthermore, there is increasing evidence suggesting associations between internal dose of PCBs and cardiovascular outcomes. OBJECTIVES: The purpose of this study is to investigate longitudinal associations of PCBs with coronary heart disease (CHD)-related outcomes in a cohort of Great Lakes sport fish consumers. METHODS: The Great Lakes Sport Fish Consumer cohort was established in the early 1990's. Eight hundred nineteen participants were followed from 1993 to 2017. Serum PCBs were measured in 1994/1995 (baseline), in 2001, and in 2004, while health history questionnaires were administered in 1996, 2003, 2010, and 2017. Cox models were used to prospectively investigate associations of total PCBs and PCB groupings, based on aryl hydrocarbon receptor activity, with incident self-reported physician diagnosis of coronary heart disease (CHD), myocardial infarction (MI), and angina pectoris. RESULTS: A 2-fold increase in phenobarbital-type PCBs was associated with a 72% increase in likelihood of self-reported incident diagnosis of CHD (HR=1.72, 95% CI: 1.06-2.81; p=0.0294). Similar results were observed for total PCBs (HR=1.68, 95% CI: 1.05-2.69; p=0.0306) and mixed methacholine/phenobarbital type (mixed-type) PCBs (HR=1.60, 95% CI: 1.02-2.52; p=0.0427), but not methacholine-type PCBs. PCBs were not strongly associated with risk of MI or angina. CONCLUSIONS: This study presents evidence that exposure to PCBs increases the risk of developing coronary heart disease. Given the large number of risk factors and causal pathways for CHD, future research is required to better understand biological mechanisms of action for PCBs on CHD.

Associations between Novel and Legacy Per- and Polyfluoroalkyl Substances in Human Serum and Thyroid Cancer: A Case and Healthy Population in Shandong Province, East China.

Per- and polyfluoroalkyl substances (PFASs) are widely detected in the environment and may cause adverse human health effects after exposure. Studies on the effect of PFASs on some health end points, including cancer, are still limited and show inconsistent results. In this research, 319 participants were recruited from Shandong Province, East China, consisting of patients with thyroid cancer and healthy controls. Seven novel and legacy PFASs were frequently detected (detection rate > 75%) in the serum samples of the participants. The concentrations of perfluorooctanoic acid (PFOA) were the highest in the case and control groups. Males showed significantly higher concentrations of PFASs than females. Exposure to PFASs was inversely associated with the risk of thyroid cancer. In the control group, we identified significant positive associations between PFASs and free thyroxine (FT4) as well as between PFOA and thyroid stimulating hormone (TSH) in females. A significant negative association between perfluorononanoic acid (PFNA) and triiodothyronine (T3) was observed in males. Our results suggest that exposure to certain PFASs could interfere with thyroid function. To our knowledge, this is the first case-control study demonstrating associations between novel and legacy PFASs in human and thyroid cancer.

Associations of exposure to metal and metal mixtures with thyroid hormones: Results from the NHANES 2007-2012.

BACKGROUND: Disrupted thyroid homeostasis plays a role in neurocognitive dysfunction and metabolic disorders. Since individuals are exposed to multiple metals simultaneously, it is important to assess the effects of metal mixtures on thyroid hormone status. This study aimed to investigate the associations of metal mixtures and individual metals with thyroid hormone levels. METHODS: Data included 2399 men and 1988 women from the 2007-2012 National Health and Nutrition Examination Survey (2007-2012). Thyroid hormones measured included total triiodothyronine (T3), total thyroxine (T4), free forms of T3 (FT3) and T4 (FT4), and thyroid stimulating hormone (TSH). We included twelve metals (arsenic, barium, cobalt, cesium, molybdenum, antimony, thallium, tungsten, and uranium from urine; cadmium, lead, and mercury from blood) in traditional linear regression models controlling for 12 metals simultaneously and in quantile-based g-computation (QGC) to assess the relative contribution of each metal as well as the overall association with thyroid hormones as a metal mixture. RESULTS: There were associations of the total metal mixture with thyroid hormones for T3 (beta: -0.023, 95% CI: -0.04, -0.01, in women), T4 (beta: -0.03, 95% CI: -0.05, -0.01, in men; beta: -0.026, 95% CI: -0.04, -0.01, in women), and the T3:T4 ratio (beta: 0.026, 95% CI: 0.01, 0.05, in men). Arsenic had negative contributions to T3 and T4. Cadmium had a positive contribution to T4 but negative contributions to T3 and T3:T4. Lead had a positive contribution to T3 and T3:T4, but a negative contribution to T4. CONCLUSION: Multiple metals as a mixture were associated with thyroid hormone levels. Arsenic, cadmium, and lead were individually associated with multiple thyroid hormones. Examination of associations of metal mixtures and individual metals with thyroid hormones can contribute to an understanding of thyroid hormone homeostasis and provide evidence for developing intervention and guidance for health promotion.

Exposure to organochlorine pesticides and the risk of type 2 diabetes in the population of East China.

Organochlorine pesticides (OCPs) have been reported to be associated with an elevated risk of type 2 diabetes, although no study has focused on such associations in Chinese populations. In this case-control study, we aimed to explore the associations between OCPs and type 2 diabetes and their potential mechanisms in a population from East China. Participants diagnosed with type 2 diabetes and nondiabetic participants from Shandong Province, East China, were enrolled in this case-control study. Six OCPs (ß-HCH, trans-chlordane, trans-nonachlor, p,p'-DDE, p,p'-DDT and mirex/kepone) were detected in more than 75% of serum samples. Logistic regression analysis and multiple linear regression analysis were used to assess the associations between OCP exposure and the outcomes. After adjusting for potential confounding factors such as age, sex and body mass index, all six OCPs showed positive associations with type 2 diabetes in a linear dose-response manner. Serum concentrations of ß-HCH and p,p'-DDE were associated with higher levels of fasting plasma glucose in participants without diabetes, although no OCPs showed significant associations with hemoglobin A1c. In addition, certain OCPs showed significantly positive associations with triglycerides, total cholesterol, and low-density lipoprotein cholesterol and negative relationships with high-density lipoprotein cholesterol in nondiabetics, indicating that OCP exposure may disrupt lipid metabolism. Findings in the current study indicated that OCPs may be a diabetogenic factor in the population of this study. To our knowledge, this is the first study to investigate the associations between OCP exposure and type 2 diabetes in a Chinese population.

Associations between Exposure to Persistent Organic Pollutants and Thyroid Function in a Case-Control Study of East China.

Animal studies have indicated that persistent organic pollutants (POPs) affect thyroid hormone homeostasis, while epidemiological studies involving human have not shown consistent results. In this study, we investigated the associations between POP exposure and thyroid function among adult population of East China. One hundred eighty-six participants diagnosed with thyroid disease and 186 participants without thyroid disease from Shandong, China were enrolled in the case-control study during 2016 to 2017. We found that POP exposure was significantly and positively associated with the risk of thyroid disease. The association of thyroid disease with a sum of 17 POPs followed a nonmonotonic dose response, with an adjusted odds ratio of 2.09 (95% confidence intervals: 1.13-3.87, p = 0.019) for the second quartile. Among 186 participants in the control group, concentrations of POPs showed negative associations with triiodothyronine (T3), free T3 (FT3), thyroxine (T4), and free T4 (FT4) in males and positive associations with T4 and FT4 in females. Taken together, these findings suggest that POP exposure can disrupt thyroid hormone homeostasis and increase the risk of thyroid disease.

Urinary arsenic concentration, airway inflammation, and lung function in the U.S. adult population.

BACKGROUND: Inorganic arsenic (iAs) is ubiquitous in the environment and has been linked to lung cancer and a number of non-malignant lung disease in both adults and children. However, most studies were conducted in populations with higher arsenic exposure levels in drinking water and relatively little epidemiologic research evaluated the impacts of low levels iAs exposure on non-malignant lung disease among populations that are not primarily exposed to arsenic through drinking water. OBJECTIVES: We assessed the associations of arsenic exposure with airway inflammation and lung function among U.S. adults aged 20-79 years using data from the National Health and Nutrition Examination Survey 2007-2012 cycles. METHODS: Two measures of arsenic exposure, urinary total arsenic and dimethylarsonic acid (DMA), were used. We calibrated these two exposure measures by regressing their concentrations by arsenobetaine and extracting the residuals to calculate estimated total arsenic and estimated DMA. Arsenic exposures were modeled as log-transformed continuous variables as well as quartile categories. Fractional exhaled nitric oxide (FENO), an indicator of respiratory inflammation, was available for participants. For lung function, the best forced expiratory volume in the first one second (FEV1), forced vital capacity (FVC), forced expiratory flow rate (FEF) 25-75%, their percent estimated values, ratios of FEV1 to FVC, and FEF 25-75% to FVC were used (i.e. FEV1/FVC and FEF/FVC). Weighted multivariable linear regression models, adjusted for potential confounders, were used to evaluate the association of arsenic exposure with airway inflammation and lung function overall, and among males and females. RESULTS: Significant associations between arsenic exposure and increased airway inflammation were found. A two-fold increase in urinary total arsenic and DMA was associated with 23.87% (95% CI: 2.66, 49.46) and 14.05% (95% CI: 1.77, 27.81) higher levels of FENO, respectively. In addition, participants in the highest quartile of urinary total arsenic had FENO levels 8.49% (95% CI: 1.13, 16.39) higher than those in the lowest quartile. These associations were similar between males and females. Limited evidence was found for the association with respect to lung function and potential modification effect of sex. CONCLUSIONS: Arsenic exposure was related to increased risk of airway inflammation but there is limited evidence of an association in relation to lung function. Future research conducted in populations with relatively lower exposure levels that are not primarily exposed to arsenic through drinking water is needed to confirm our findings.

Prenatal exposure to nitrate in drinking water and the risk of congenital anomalies.

BACKGROUND: Nitrate is a common water contaminant that has been associated with birth defects, although the evidence is limited. The purpose of this study was to examine whether maternal consumption of nitrate through drinking water is associated with an increased risk of congenital anomalies. METHODS: The study included a total of 348,250 singletons births from the state of Missouri between January 1, 2004 and December 31, 2008. Individual-level birth defect data and maternal and child characteristics were obtained from the Missouri birth defects registry and state vital statistics records. Outcomes were linked with county-specific monthly estimates of the nitrate concentration in finished water, based on data collected for compliance with the Safe Drinking Water Standard. Poisson models were fit to examine the association between nitrate exposure and birth defects. Average nitrate exposure during the first trimester and over 12 months prior to birth were modeled as continuous variables. Sensitivity analyses included restriction of the sample to counties with <20% and <10% private well usage to reduce exposure misclassification as well as limiting the analyses to residents of rural counties only to account for potential confounding by urbanicity. RESULTS: Estimated water concentrations of nitrate were generally low and below the Environmental Protection Agency's maximum contaminant level of 10 mg/L. Nitrate exposure was associated with a significantly increased risk of limb deficiencies (RR for 1 mg/L (RR1) = 1.26, 95% CI = 1.05, 1.51) in models without well restriction. Nitrate was also weakly associated with an increased risk of congenital heart defects (RR1 = 1.13, 95%CI = 0.93, 1.51) and neural tube defects (RR1 = 1.18, 95%CI = 0.93, 1.51) in models with well restriction (<10%). CONCLUSION: The positive associations found between nitrate exposure via drinking water and congenital abnormalities are largely consistent with some previous epidemiologic studies. The results of this study should be interpreted with caution given limitations in our ability to estimate exposures and the lack information on some risk factors for congenital abnormalities. Our findings may have serious policy implications given that exposure levels in our study were well below current EPA standards for nitrate in drinking water.

Association of methylmercury intake from seafood consumption and blood mercury level among the Asian and Non-Asian populations in the United States.

BACKGROUND: MeHg is a well-established neurotoxicant for fetal brain growth and development and has been shown to increase the risk of cardiovascular disease in aging populations. In the U.S., Asian populations are of particular concern because of their seafood consumption behaviors. OBJECTIVES: Our objective was to calculate the average daily MeHg intake (ADMI) from seafood and to assess the relationship between ADMI with blood methylmercury (BMeHg) concentrations, specifically among women of reproductive age (WORA) and adults ≥ 50 years of age. METHODS: We estimated ADMI from seafood using the 30-day fish consumption data from the NHANES 2011-2014 datasets. Using multivariable linear regression, we estimated the proportional change in mean BMeHg associated with a doubling of the ADMI. Further, correlations between ADMI and BMeHg were compared between Asians and other racial/ethnic groups. RESULTS: Our analysis found both Asian WORA and Asian adults age ≥ 50 years old had significantly higher BMeHg levels and ADMI than their Non-Asian counterparts. Correlations between ADMI from seafood and blood Hg levels were stronger among Asian WORA than among Non-Asian WORA. Key fish species that influenced the dietary MeHg intake for Asians were mackerel, tuna, and "other known/unknown fish species". CONCLUSION: We confirmed that Asian populations have higher MeHg intake than the Non-Asian population in the U.S. and seafood intake is a key predictor of blood Hg concentration, especially among Asian women of reproductive age. Future studies should incorporate information on other known and unknown fish species that are frequently consumed by Asian populations and different parts and fish organs eaten to better understand determinants of MeHg exposure.

Arsenic in drinking water and adverse birth outcomes in Ohio.

BACKGROUND: Arsenic in drinking water has been associated with adverse reproductive outcomes in areas with high levels of naturally occurring arsenic. Less is known about the reproductive effects of arsenic at lower levels. OBJECTIVES: This research examined the association between low-level arsenic in drinking water and small for gestational age (SGA), term low birth weight (term LBW), very low birth weight (VLBW), preterm birth (PTB), and very preterm birth (VPTB) in the state of Ohio. METHODS: Exposure was defined as the mean annual arsenic concentration in drinking water in each county in Ohio from 2006 to 2008 using Safe Drinking Water Information System data. Birth outcomes were ascertained from the birth certificate records of 428,804 births in Ohio from the same time period. Multivariable generalized estimating equation logistic regression models were used to assess the relationship between arsenic and each birth outcome separately. Sensitivity analyses were performed to examine the roles of private well use and prenatal care utilization in these associations. RESULTS: Arsenic in drinking water was associated with increased odds of VLBW (AOR 1.14 per µg/L increase; 95% CI 1.04, 1.24) and PTB (AOR 1.10; 95% CI 1.06, 1.15) among singleton births in counties where <10% of the population used private wells. No significant association was observed between arsenic and SGA, or VPTB, but a suggestive association was observed between arsenic and term LBW. CONCLUSIONS: Arsenic in drinking water was positively associated with VLBW and PTB in a population where nearly all (>99%) of the population was exposed under the current maximum contaminant level of 10µg/L. Current regulatory standards may not be protective against reproductive effects of prenatal exposure to arsenic.

Livestock and poultry density and childhood cancer incidence in nine states in the USA.

BACKGROUND: Parental occupational and childhood exposures to farm animals have been positively associated with childhood brain tumors, whereas associations with childhood leukemia are equivocal. The developing immune system may be influenced by allergen, virus, or other exposures from animal sources, which may contribute to childhood cancer incidence. METHODS: Incident cancers (acute lymphoblastic leukemia [ALL], acute myeloid leukemia [AML], central nervous system [CNS], peripheral nervous system [PNS]) for children aged 0-4 diagnosed between 2003 and 2008 were obtained from nine National Cancer Institute Surveillance, Epidemiology and End Results (SEER) registries and were linked to U.S. Census of Agriculture data from 2002 and 2007 by county of diagnosis. Animal densities (animal units [AU]/km2; one animal unit is 1000 pounds of animal weight) were estimated for hogs, cattle, chickens (layers and broilers, separately), equine (horses, ponies, mules, burros, donkeys), goats, sheep, turkeys, and total animals. Animal density was examined in models as both continuous (AU per km2) and categorical variables (quartiles). Animal operation densities (per km2) by size of operation (cattle, hogs, chickens, sheep) were modeled continuously. Rate ratios and 95% confidence intervals were estimated using Poisson regression. RESULTS: We found positive associations between AML and broiler chicken densities (RRper 10AU/km2 = 1.14, 95% CI = 1.02-1.26). ALL rates increased with densities of hog operations (RRper operation/100km2 = 1.06, 95% CI = 1.02-1.11). PNS cancer rates were inversely associated with layer chicken density (RRper log of AU/km2 = 0.94, 95% CI = 0.89-0.99). No association was found between any cancer type and densities of cattle, equine, or goats. CONCLUSIONS: Although limited by the ecologic study design, some of our findings are novel and should be examined in epidemiological studies with individual level data.

Arsenic in drinking water and prostate cancer in Illinois counties: An ecologic study.

BACKGROUND: Inorganic arsenic is a lung, bladder, and skin carcinogen. One of the major sources of exposure to arsenic is through naturally contaminated drinking water. While positive associations have been observed between arsenic in drinking water and prostate cancer, few studies have explored this association in the United States. OBJECTIVES: To evaluate the association between inorganic arsenic concentrations in community water systems and prostate cancer incidence in Illinois using an ecologic study design. METHODS: Illinois Environmental Protection Agency data on arsenic concentrations in drinking water from community water systems throughout the state were linked with county-level prostate cancer incidence data from 2007 to 2011 from the Illinois State Cancer Registry. Incidence rates were indirectly standardized by age to calculate standardized incidence ratios (SIRs) for each county. A Poisson regression model was used to model the association between county-level SIRs and mean arsenic tertile (0.33-0.72, 0.73-1.60, and 1.61-16.23ppb), adjusting for potential confounders. RESULTS: For counties with mean arsenic levels in the second tertile, the SIR was 1.05 (95% CI: 0.96-1.16). For counties with mean arsenic levels in the third tertile, the SIR was 1.10 (95% CI: 1.03-1.19). There was a significant linear dose-response relationship observed between mean arsenic levels and prostate cancer incidence (p for trend=0.003). CONCLUSIONS: In this ecologic study, counties with higher mean arsenic levels in community water systems had significantly higher prostate cancer incidence. Individual-level studies of prostate cancer incidence and low-level arsenic exposure are needed.

Diabetes Screening in US Women With a History of Gestational Diabetes, National Health and Nutrition Examination Survey, 2007-2012.

INTRODUCTION: Women with a history of gestational diabetes mellitus (GDM) are at increased risk for developing type 2 diabetes mellitus. We examined individual, socioeconomic, and health care use characteristics of women with a history of GDM and the association of those characteristics with diabetes screening, and we estimated their rates of undiagnosed prediabetes and diabetes. METHODS: Using 3 cycles of the National Health and Nutrition Examination Survey (2007-2008, 2009-2010, and 2011-2012), we identified 284 women with a history of GDM who were eligible for diabetes screening. Screening status was defined by self-report of having had a blood test for diabetes within the prior 3 years. Undiagnosed prediabetes and diabetes were assessed by hemoglobin A1c measurement. RESULTS: Among women with a history of GDM, 67% reported diabetes screening within the prior 3 years. Weighted bivariate analyses showed screened women differed from unscreened women in measured body mass index (BMI) category (P = .01) and number of health visits in the prior year (P = .001). In multivariable analysis, screening was associated with a greater number of health visits in the prior year (1 visit vs 0 visits, adjusted odds ratio [AOR], 1.91; 95% confidence interval [CI], 0.71-5.18; 2 or 3 visits, AOR, 7.05; and ≥4 visits, AOR, 5.83). Overall, 24.4% (95% CI, 18.3%-31.7%) of women had undiagnosed prediabetes and 6.5% (95% CI, 3.7%-11.3%) had undiagnosed diabetes. CONCLUSION: More health visits in the prior year was associated with receiving diabetes screening. Fewer opportunities for screening may delay early detection, clinical management, and prevention of diabetes. Prediabetes in women with a history of GDM may be underrecognized and inadequately treated.

Associations between bone mineral density and urinary phthalate metabolites among post-menopausal women: a cross-sectional study of NHANES data 2005-2010.

Bone mineral density (BMD) decreases with age, especially among post-menopausal women. Exposures to endocrine disruptors, such as phthalate diesters, could alter BMD through a variety of unidentified mechanisms. A hypothesis-generating study investigated associations between urinary phthalate metabolites and BMD at the femoral neck and spine in post-menopausal women (n = 480) participating in the National Health and Nutrition Examination Survey, from 2005 to 2010. Mono-ethyl phthalate (MEP), molar sum of low molecular weight metabolites (mono-n-butyl phthalate (MNBP), mono-isobutyl phthalate (MIBP), MEP), molar sum of estrogenic metabolites (MNBP, MIBP, MEP, mono-benzyl phthalate (MBZP)), and an estrogenic equivalency factor were negatively associated with spinal BMD. Some associations were modified by age or BMI. The cross-sectional study design, uncertainty regarding the critical time window of exposure, the potential for exposure misclassification, and residual confounding limit our abilities to draw causal conclusions regarding phthalate metabolites and BMD in post-menopausal women. Future studies should address these limitations.

Associations of lead and cadmium with sex hormones in adult males.

Heavy metal exposures are ubiquitous in the environment and their relation to sex hormones is not well understood. This paper investigates the associations between selected heavy metals (lead and cadmium) and sex hormones (testosterone, free testosterone, estradiol, free estradiol) as well as other major molecules in the steroid biosynthesis pathway (androstanedione glucuronide and sex-hormone binding globulin (SHBG)). Blood lead and cadmium were selected as biomarkers of exposure, and tested for associations in males using National Health and Nutritional Examination Survey (NHANES) data from 1999-2004. After adjustment for age, race, body mass index, smoking status, diabetes and alcohol intake, blood lead was positively associated with testosterone and SHBG while blood cadmium was positively associated with SHBG. After controlling for additional heavy metal exposure, the associations between lead and testosterone as well as cadmium and SHBG remained significant. Furthermore, the association between blood lead and testosterone was modified by smoking status (P for interaction=0.011), diabetes (P for interaction=0.021) and blood cadmium (P for interaction=0.029). The association between blood cadmium and SHBG levels was modified by blood lead (P for interaction=0.004). This study is the most comprehensive investigation to date regarding the association between heavy metals and sex hormones in males.

Agricultural crop density and risk of childhood cancer in the midwestern United States: an ecologic study.

BACKGROUND: There is limited evidence for an association between agricultural pesticide exposure and certain types of childhood cancers. Numerous studies have evaluated exposure to pesticides and childhood cancer and found positive associations. However, few studies have examined the density of agricultural land use as a surrogate for residential exposure to agricultural pesticides and results are mixed. We examined the association of county level agricultural land use and the incidence of specific childhood cancers. METHODS: We linked county-level agricultural census data (2002 and 2007) and cancer incidence data for children ages 0-4 diagnosed between 2004 and 2008 from cancer registries in six Midwestern states. Crop density (percent of county area that was harvested) was estimated for total agricultural land, barley, dry beans, corn, hay, oats, sorghum, soybeans, sugar beets, and wheat. Rate ratios and 95% confidence intervals were estimated using generalized estimating equation Poisson regression models and were adjusted for race, sex, year of diagnosis, median household income, education, and population density. RESULTS: We found statistically significant exposure-response relationships for dry beans and total leukemias (RR per 1% increase in crop density = 1.09, 95% CI = 1.03-1.14) and acute lymphoid leukemias (ALL) (RR = 1.10, 95% CI = 1.04-1.16); oats and acute myeloid leukemias (AML) (RR = 2.03, 95% CI = 1.25, 3.28); and sugar beets and total leukemias (RR = 1.11, 95% CI = 1.04, 1.19) and ALL (RR = 1.11, 95% CI = 1.02, 1.21). State-level analyses revealed some additional positive associations for total leukemia and CNS tumors and differences among states for several crop density-cancer associations. However, some of these analyses were limited by low crop prevalence and low cancer incidence. CONCLUSIONS: Publicly available data sources not originally intended to be used for health research can be useful for generating hypotheses about environmental exposures and health outcomes. The associations observed in this study need to be confirmed by analytic epidemiologic studies using individual level exposure data and accounting for potential confounders that could not be taken into account in this ecologic study.

Thyroid-related Hormones and Hypertension Incidence in Middle-Aged and Older Hispanic/Latino Adults: The HCHS/SOL Study.

Background: Thyroid-related hormones act to regulate metabolic pathways and blood pressure (BP). However, the relationship of TSH and peripheral thyroid hormones and the role of the hypothalamic-pituitary-thyroid axis on hypertension development is not fully understood. We assessed sex-specific associations of thyroid-related hormones with BP and hypertension in Hispanic/Latino adults followed for 6 years. Methods: We studied 1789 adults, ages 45 to 74, free of diabetes at baseline from a subcohort of the Hispanic Community Health Study/Study of Latinos. We assessed TSH, free T4 (FT4), T3, and various indicators of thyroid axis. Using multivariable linear and Poisson regression adjusted for survey design and confounding variables, we estimated a priori sex-specific associations of thyroid-related hormones with changes in BP and hypertension development. Results: In men and women, TSH and TSH/FT4 ratios were associated with changes in diastolic BP and T3 with changes in pulse pressure and the development of hypertension from prehypertension. In men, a 1-SD increase in TSH [incident rate ratio (IRR) = 1.42; 95% confidence interval (CI): 1.15, 1.75] and TSH/FT4 ratio (IRR = 1.20; 95% CI: 1.07, 1.35) were positively associated with the development of hypertension from prehypertension while the TSH/FT4 ratio (IRR = 0.85; 95% CI: .72, 1.00) was protective in women. We observed sex-specific differences in associations of the T3/FT4 ratio and indices of pituitary sensitivity to thyroid hormones with changes in pulse pressure and hypertension development. Conclusion: Thyroid-related hormones are associated with sex-specific changes in BP and hypertension among Hispanic/Latino adults consistent with selected studies conducted in other populations. Mechanisms underlying associations of pituitary sensitivity to thyroid hormones with BP and hypertension development warrant further study.

Thyroid Hormones and Diabetes in Euthyroid Hispanic/Latino Adults of Diverse Backgrounds: HCHS/SOL.

Context: Previous studies have demonstrated associations of endogenous thyroid hormones with diabetes; less is known about stages of diabetes development at which they are operative, mechanisms of associations, and the role of the hypothalamic-pituitary-thyroid axis. Objective: This study examined associations of thyroid hormones with incident prediabetes and diabetes and with changes in glycemic traits in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), the largest cohort of Hispanic/Latino adults with diverse backgrounds in the United States. Methods: The study includes 592 postmenopausal euthyroid women and 868 euthyroid men aged 45 to 74 years without diabetes at baseline participating in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Baseline hormones included thyrotropin (TSH), free thyroxine (FT4), total triiodothyronine (T3), and indices calculated from thyroid hormones evaluating pituitary sensitivity to thyroid hormone. Transitions to diabetes and prediabetes, and changes in glycemic traits determined at the 6-year follow-up visit, were examined using multivariable Poisson and linear regressions. Results: Among women, T3 (incident rate ratio [IRR] = 1.65; 95% CI, 1.22-2.24; P = .001) and TSH (IRR = 2.09; 95% CI, 1.01-4.33; P = .047) were positively, while FT4 (IRR = 0.59; 95% CI, 0.39-0.88; P = .011) was inversely, associated with transition from prediabetes to diabetes. Among men, the T3/FT4 ratio was positively associated with transition from normoglycemia to prediabetes but not from prediabetes to diabetes. Indices measuring sensitivity of the pituitary to thyroid hormone suggested increased sensitivity in men who transitioned from prediabetes to diabetes. Conclusion: Positive associations in women of T3 and TSH and inverse associations of FT4, as well as inverse associations of thyroid indices in men with transition from prediabetes to diabetes, but not from normoglycemia to diabetes, suggest decreased pituitary sensitivity to thyroid hormones in women and increased sensitivity in men later in the development of diabetes.

Association of Blood Total Mercury with Dyslipidemia in a sample of U.S. Adolescents: Results from the National Health and Nutrition Examination Survey Database, 2011-2018.

Background: Abnormal lipid profiles in adolescents predict metabolic and cardiovascular diseases in adulthood. While seafood consumption is the primary source of mercury exposure, it also provides beneficial nutrients such as omega-3 fatty acids (O3FA). Prior studies indicate that blood total mercury (TBHg) has endocrine disrupting effects and may be associated with abnormal lipid profiles in adolescents. However, the impact of beneficial nutrients on this relationship has not been examined. Our study investigated the relationship of TBHg with dyslipidemia and lipid profiles and potential confounding and modification of these relationships by sex, body mass index (BMI), selenium and O3FA from seafood consumption. Methods: We examined 1,390 National Health and Nutrition Examination Survey participants 12-19 years of age from the 2011-2018 cycles. Using logistic and linear regression adjusted for survey design variables and stratified by sex a priori, we estimated the associations of TBHg and methylmercury with dyslipidemia, and with total cholesterol (TC), high (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and triglycerides. Results: The geometric mean of TBHg in this adolescent population was 0.44 µg/L. After controlling for socio-demographic covariates, BMI, serum selenium, age at menarche (females only) and average daily intake of O3FA; TBHg was significantly associated with higher TC levels (ß=3.34, 95% CI: 0.19, 6.50; p<0.05) in females but not males. Methyl Hg was also associated with increased TC, as well as decreased HDL-C in females but not males. We did not find significant associations of Hg exposure with dyslipidemia, LDL-C or triglycerides levels in either male or female adolescents. However, we observed evidence of effect modification by BMI and serum selenium for associations of TBHg with TC levels in male and female adolescents, respectively. Conclusion: Our findings of elevated TC levels in females but not males necessitates further research to better understand the underlying mechanisms driving these sex-specific associations.

Association of Acculturation and Hispanic/Latino Background with Endogenous Sex and Thyroid-Related Hormones Among Middle-Aged and Older Hispanic/Latino Adults: the HCHS/SOL Study.

BACKGROUND: Hormones are linked to cardiometabolic diseases and may be impacted by acculturation though multiple mechanisms. We evaluated associations of Hispanic/Latino background and acculturation with levels of sex- and thyroid-related hormones and the potential mediating effect of adiposity, lifestyle factors, and sleep apnea syndrome on these associations. METHODS: We studied 1789 adults, aged 45-74, from a sub-cohort of the Hispanic Community Health Survey/Study of Latinos. Peri/pre-menopausal women and individuals on medications related to hormones were excluded. Our study assessed eleven sex- and thyroid-related hormones, Hispanic/Latino background, and five acculturation measures. Associations were assessed using multivariable linear and logistic regression adjusted for survey design and confounding variables. We explored potential mediation using a path analysis. RESULTS: In postmenopausal women, acculturation score-MESA was associated with decreased thyroid-stimulating hormone (ß = - 0.13;95%CI = - 0.22, - 0.03) while age at immigration greater than the median (vs US-born) was associated with decreased (ß = - 14.6; 95%CI = - 28.2, - 0.99) triiodothyronine (T3). In men, language acculturation and acculturation score-MESA were associated with increased estradiol and sex hormone-binding globulin (SHBG) while age at immigration greater and lesser than the median (vs US-born) was associated with decreased SHBG. Hispanic/Latino background (Mexicans as reference) were selectively associated with sex- and thyroid-related hormone levels in both sexes. Current smoking and sleep apnea syndrome partially mediated the association of Cuban and Puerto Rican heritage (vs Mexican) with T3 levels in men and postmenopausal women, respectively. CONCLUSION: Selected acculturation measures were associated with thyroid-related hormones in postmenopausal women and sex-related hormones in men. Understanding the mechanisms involved in the relationship of acculturation and Hispanic/Latino background with hormones warrants additional investigation.

Sex Hormones and Diabetes in 45- to 74-year-old Men and Postmenopausal Women: The Hispanic Community Health Study.

Previous studies demonstrated associations of endogenous sex hormones with diabetes. Less is known about their dynamic relationship with diabetes progression through different stages of the disease, independence of associations, and role of the hypothalamic-pituitary gonadal axis. The purpose of this analysis was to examine relationships of endogenous sex hormones with incident diabetes, prediabetes, and diabetes traits in 693 postmenopausal women and 1015 men aged 45 to 74 years without diabetes at baseline participating in the Hispanic Community Health Study/Study of Latinos and followed for 6 years. Baseline hormones included estradiol, luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and, in men, testosterone and bioavailable testosterone. Associations were analyzed using multivariable Poisson and linear regressions. In men, testosterone was inversely associated with conversion from prediabetes to diabetes (incidence rate ratio [IRR] for 1 SD increase in testosterone: 0.821; 95% CI, 0.676, 0.997; P = 0.046), but not conversion from normoglycemia to prediabetes. Estradiol was positively associated with increase in fasting insulin and homeostatic model assessment of insulin resistance. In women, SHBG was inversely associated with change in glycosylated hemoglobin, postload glucose, and conversion from prediabetes to diabetes (IRR = 0.62; 95% CI, 0.44, 0.86, P = 0.005) but not from normoglycemia to prediabetes. Relationships with other hormones varied across glycemic measures. Stronger associations of testosterone and SHBG with transition from prediabetes to diabetes than from normoglycemic to prediabetes suggest they are operative at later stages of diabetes development. Biologic pathways by which sex hormones affect glucose homeostasis await future studies.