Perfluoroalkyl Substances and Abdominal Aortic Calcification.

OBJECTIVE: To evaluate if serum perfluoroalkylated substances (PFAS) were associated with abdominal aortic calcification (AAC). METHODS: We used weighted logistic regression to investigate the gender-specific association between PFAS serum levels and AAC more than or equal to 6 from dual-energy X-ray absorptiometry (DXA) scans of the thoraco-lumbar spine from National Health and Nutrition Examination Survey 2013-2014 survey participants aged more than or equal to 40 years. RESULTS: After adjusting for confounding, none of log-transformed perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS), or perfluorononanoic acid (PFNA) were significantly associated with AAC for either men or women (adjusted odds ratios [ORs] ranged from 0.80 to 1.33, P  > 0.05 each). For PFOA and PFOS, the association was positive only in women (although the difference was not statistically significant in either case). CONCLUSION: These findings do not provide general support for a relationship of PFAS exposure to AAC, although the results show a need for gender-specific consideration in a larger dataset.

Per- and Polyfluoroalkyl Substance and Cardio Metabolic Markers in Firefighters.

OBJECTIVE: To evaluate if serum polyfluoroalkyl substances (PFAS) were associated with cardiometabolic markers. METHODS: Serum PFAS were evaluated in 38 Arizona firefighters and 49 participants from the 2009 to 2010 National Health and Nutrition Examination Survey (NHANES). Cardiometabolic markers including carotid intima-medial thickness (CIMT) were measured in the firefighters. RESULTS: Firefighters had elevated perfluorohexane sulfonic acid (PFHxS) and lower perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUA) compared to NHANES participants; for nine of the other 12 PFAS the values were not significantly different. There were significant negative associations among firefighters between perfluorodecanoic acid (PFDeA) and total cholesterol and PFUA and interleukin-6. PFAS concentrations were not associated with CIMT. CONCLUSION: PFHxS levels were elevated in firefighters compared to NHANES subjects. Serum PFAS concentrations were not associated with increased cardiometabolic risk measures in this population of firefighters.

Perfluoroalkyl Substances and Metabolic Syndrome in Firefighters: A Pilot Study.

OBJECTIVE: To compare association of perfluoroalkyl substances (PFASs) with metabolic syndrome (MetS) profile among firefighters (FF) at airport to suburban FF. METHODS: Cross-sectional exploratory study, 47 men FF aged 18 to 62 years were enrolled from two fire departments in Ohio. Association between MetS outcome and log transformed serum concentrations of four PFASs was evaluated using multivariable logistic regression. RESULTS: PFASs serum concentrations were 18% to 74% higher in FF than the general population, and 21% to 62% higher in airport FF than suburban FF. Compared with US general population, an elevated risk of hypertension was noted in FF, but no significant association between PFASs and MetS was found. CONCLUSIONS: Current serum PFASs in FF are not associated with MetS risk.

Perfluoroalkyl substances, bone density, and cardio-metabolic risk factors in obese 8-12 year old children: A pilot study.

BACKGROUND AND OBJECTIVE: Perfluoroalkyl substances (PFASs), including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), have been associated with adverse bone, and metabolic changes in adults. However association of PFASs with bone health in children is understudied. Considering their role as endocrine disruptors, we examined relationships of four PFASs with bone health in children. METHODS: In a cross sectional pilot study, 48 obese children aged 8-12 years were enrolled from Dayton's Children Hospital, Ohio. Anthropometric, clinical and biochemical assessments of serum were completed. Serum PFASs were measured by UPLC-ESI-MS/MS. In a subset of 23 children, bone health parameters were measured using calcaneal quantitative ultrasound (QUS). RESULTS: While PFASs exposure was associated with a consistent negative relationship with bone health parameters, among four PFASs tested, only PFNA showed a significant negative relationship with bone parameter (ß [95% CI], = - 72.7 [- 126.0, - 19.6], p = .010). PFNA was also associated with raised systolic blood pressure (p = .008), low density lipoprotein cholesterol (LDL-C; p < .001), and total cholesterol (TC; p = .014). In addition, both PFOA and PFOS predicted elevation in LDL-C, and PFOA predicted increased TC, as well. In this analysis, PFASs were not strongly related to thyroid hormones, 25-hydroxy vitamin D, liver enzymes, or glucose homeostasis. CONCLUSION: PFASs exposure in obese children may play a role in adverse skeletal and cardiovascular risk profiles.

Association of Perfluoroalkyl Substances, Bone Mineral Density, and Osteoporosis in the U.S. Population in NHANES 2009-2010.

BACKGROUND: Perfluoroalkyl substances (PFASs), including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), are detectable in the serum of 95% of the U.S. OBJECTIVE: Considering the role of PFASs as endocrine disruptors, we examined their relationships with bone health. METHODS: The association between serum PFAS concentration and bone mineral density at total femur (TFBMD), femoral neck (FNBMD), lumbar spine (LSBMD), and physician-diagnosed osteoporosis was assessed in 1,914 participants using data from the National Health and Nutritional Examination Survey 2009-2010. RESULTS: The mean age of the participants was 43 years. Men had higher serum PFAS concentrations than women (p < 0.001) except for PFNA. In both sexes, serum PFOS concentrations were inversely associated with FNBMD (p < 0.05). In women, significant negative associations were observed for natural log (ln)-transformed PFOS exposure with TFBMD and FNBMD, and for ln-transformed PFOA exposure with TFBMD (p < 0.05). In postmenopausal women, serum PFOS was negatively associated with TFBMD and FNBMD, and PFNA was negatively associated with TFBMD, FNBMD, and LSBMD (all p < 0.05). With one log unit increase in serum PFOA, PFHxS, and PFNA, osteoporosis prevalence in women increased as follows: [adjusted odds ratios (aORs)] 1.84 (95% CI: 1.17, 2.905), 1.64 (95% CI: 1.14, 2.38), and 1.45 (95% CI: 1.02, 2.05), respectively. In women, the prevalence of osteoporosis was significantly higher in the highest versus the lowest quartiles of PFOA, PFHxS, and PFNA, with aORs of 2.59 (95% CI: 1.01, 6.67), 13.20 (95% CI: 2.72, 64.15), and 3.23 (95% CI: 1.44, 7.21), respectively, based on 77 cases in the study sample. CONCLUSION: In a representative sample of the U.S. adult population, serum PFAS concentrations were associated with lower bone mineral density, which varied according to the specific PFAS and bone site assessed. Most associations were limited to women. Osteoporosis in women was also associated with PFAS exposure, based on a small number of cases. CITATION: Khalil N, Chen A, Lee M, Czerwinski SA, Ebert JR, DeWitt JC, Kannan K. 2016. Association of perfluoroalkyl substances, bone mineral density, and osteoporosis in the U.S. population in NHANES 2009-2010. Environ Health Perspect 124:81-87; http://dx.doi.org/10.1289/ehp.1307909.

Endocrine disruptive compounds and cardio-metabolic risk factors in children.

The endocrine disrupting chemicals (EDC) are exogenous chemicals that can disrupt hormonal signaling system. EDCs are ubiquitous in our environment and many EDC are detectable in humans. With the increasing obesity prevalence in children it is imperative to explore the role of EDC as obesogens. This review summarizes recent epidemiological evidence regarding impact of these EDC on weight gain and metabolic outcomes in children. The EDCs include pharmaceuticals, pesticides, industrial by-products, and cigarette smoke. Current evidence suggests a link between early life exposure to some industrial by-products, synthetic hormones and cigarette smoke with weight gain. However, there is inconclusive evidence of an association between exposure to fungicides, dioxin, phytoestrogens, flame retardants, heavy metals and childhood obesity.

Progression from metabolically benign to at-risk obesity in perimenopausal women: a longitudinal analysis of study of women across the nation (SWAN).

BACKGROUND: Little is known about the natural history of progression from a metabolically benign overweight/obese (MBO) to at-risk overweight/obese (ARO) phenotype. Improved understanding would help clinicians focus on controlling risk factors that predispose an obese individual to progression. METHODS: Using discrete-time proportional hazard modeling on data from the Study of Women's Health Across the Nation (SWAN), we examined the incident progression from MBO (less than two metabolic syndrome abnormalities) to ARO (two or more metabolic syndrome abnormalities) and factors associated with progression over a 7-year period. RESULTS: Of 866 MBO women at baseline, 43% progressed to the ARO phenotype. Compared with those who remained MBO, those who progressed had higher baseline BMI and a higher prevalence of cardiometabolic abnormalities (elevated glucose, triglycerides, blood pressure and low high-density lipoprotein cholesterol). In multivariable analyses, an increase in body mass index was associated with a modest increase in the risk of progression. Although all cardiometabolic abnormalities were associated with an increased risk, the baseline impaired fasting glucose showed the strongest association with the risk of progression [hazard ratio 3.24; 95% confidence interval 2.10, 4.92; P < .001]. Physical activity played a protective role in decreasing the risk of progression [hazard ratio 0.86; 95% confidence interval 0.80, 0.92; P < .001]. CONCLUSIONS: Increasing obesity and the presence of cardiometabolic abnormalities increase the risk of progression, whereas physical activity is the only lifestyle factor protective against progression from metabolically benign to the at-risk overweight/obese phenotype, a state that is unanimously associated with an elevated risk of cardiovascular morbidity and mortality.

Hyperandrogenic oligomenorrhea and metabolic risks across menopausal transition.

CONTEXT: Although there is evidence of metabolic risks in young women with irregular menses and androgen excess, persistence of risks after menopause is unclear. OBJECTIVE: The objective of the study was to determine the impact of menopause on the cardiometabolic profile in women with high androgens and a history of menstrual irregularity. METHODS: Study of Women's Health Across the Nation is a longitudinal cohort study. Data from 1929 women without metabolic syndrome (MetS) at baseline were analyzed for incidence of MetS, self-reported stroke, and myocardial infarction. Cox hazard ratios (HRs) were estimated, adjusting for age, ethnicity, body mass, smoking, menopausal status, and study site. RESULTS: Among MetS-free women at baseline, 497 new cases were identified during 20 249 woman-years of follow-up over 12 years. Women with hyperandrogenemia (HA) and oligomenorrhea (Oligo) developed incident cases of MetS at a comparable rate compared with their counterparts: eumenorrheic, normoandrogenic women [HR 1.4 (0.9-2.2)], oligomenorrheic, normoandrogenic women [HR 1.3 (0.8-2.2)], and eumenorrheic hyperandrogenic women [HR 1.2 (0.7-1.8)]. Smoking and obesity were the strongest predictors of incident MetS. There was no significant difference in incidence of self-reported stroke or MI by HA/Oligo status. CONCLUSIONS: Longitudinal evidence suggests that a history of androgen excess and menstrual irregularity is not associated with worsening of metabolic health after menopause. Our findings challenge the notion that a history of concurrent HA and Oligo reflects ongoing cardiometabolic risk in postmenopausal women.

Longitudinal assessment of the menopausal transition, endogenous sex hormones, and perception of physical functioning: the Study of Women's Health Across the Nation.

BACKGROUND: To evaluate the longitudinal associations between menopausal status, related hormonal changes, and level of self-reported physical functioning. METHODS: Study included 2,495 women (age: 45-57 between 2000 and 2001) from the Study of Women's Health Across the Nation. Physical functioning scale of the Medical Outcomes Study Short-Form (SF-36; score 0-100) was categorized as: no limitation (86-100), moderate limitation (51-85), and substantial limitation (0-50). Study variables were collected between 2000 (visit-04) and 2011 (visit-12) at five timepoints. Statistical models were adjusted for age at visit-04, time since visit-04, ethnicity, site, economic status, level and change in body mass index, level and change in physical activity, and presence of comorbid conditions. RESULTS: In final models, natural and surgical postmenopausal women had significantly higher odds of functional limitation, compared with premenopausal women. Less reduction in estradiol and testosterone since visit-04 were significantly associated with lower odds of functional limitation, while greater increase in sex hormone-binding globulin was associated with higher odds of functional limitation. CONCLUSIONS: Our findings suggest the menopause-related changes in endogenous sex hormones as a possible mechanism of action to explain the greater limitation in physical functioning reported in women at midlife.

Associations between bone mineral density, grip strength, and lead body burden in older men.

OBJECTIVES: To study the association between blood lead concentration (BPb) and bone mineral density (BMD), physical function, and cognitive function in noninstitutionalized community-dwelling older men. DESIGN: Cross-sectional study. SETTING: University of Pittsburgh clinic, Pittsburgh, Pennsylvania. PARTICIPANTS: Non-Hispanic Caucasian men aged 65 and older (N = 445) recruited as a subset of a prospective cohort for the Osteoporotic Fractures in Men Study. MEASUREMENTS: BPb was measured in 2007/08. From 2007 to 2009, BMD (g/cm(2)) was measured using dual-energy X-ray absorptiometry. At the same time, physical performance was measured using five tests: grip strength, leg extension power, walking speed, narrow-walk pace, and chair stands. Cognitive performance was assessed using the modified Mini-Mental State Examination and the Trail-Making Test Part B. Participants were categorized into quartiles of BPb. Multivariate regression analysis was used to evaluate the independent relationship between BPb, BMD, and cognitive and physical function. RESULTS: Mean BPb ± standard deviation was 2.25 ± 1.20 µg/dL (median 2 µg/dL, range 1-10 µg/dL). In multivariate-adjusted models, men in higher BPb quartiles had lower BMD at femoral neck and total hip (P-trend < .001 for both). Men with higher BPb had lower age-adjusted score for grip strength (P-trend < .001), although this association was not significant in multivariate-adjusted models (P-trend < .15). BPb was not associated with lumbar spine BMD, cognition, leg extension power, walking speed, narrow-walk pace, or chair stands. CONCLUSION: Environmental lead exposure may adversely affect bone health in older men. These findings support consideration of environmental exposure in age-associated bone fragility.

Bisphenol A and cardiometabolic risk factors in obese children.

BACKGROUND AND OBJECTIVE: Bisphenol-A (BPA) is an endocrine disruptor (ED) that has been associated with obesity and metabolic changes in liver in humans. Non-alcoholic fatty liver disease (NAFLD) affects 40% of all obese children in the United States. Association of BPA with NAFLD in children is poorly understood. We investigated if BPA might play a role. METHODS: In a cross sectional study of 39 obese and overweight children aged 3-8 years enrolled from the Children Medical Center of Dayton, Ohio, anthropometric, clinical and biochemical assessment of serum samples were conducted. Urinary BPA was measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and was adjusted for urinary creatinine BPA (creatinine) using linear regression and spline analyses. RESULTS: Higher urinary BPA (creatinine) concentration in overweight and obese children was associated with increasing free thyroxine. In male children BPA (creatinine) decreased with age, and was associated with elevated liver enzyme aspartate aminotransferase and diastolic blood pressure. The association of BPA (creatinine) persisted even after adjusting for age and ethnicity. Also in males, BPA concentration unadjusted for creatinine was significantly associated with serum fasting insulin and homeostasis model assessment for insulin resistance (HOMA-IR) showing non-monotonic exposure-response relationship. CONCLUSION: Urinary BPA in obese children, at least in males is associated with adverse liver and metabolic effects, and high diastolic blood pressure.

Mood symptoms after natural menopause and hysterectomy with and without bilateral oophorectomy among women in midlife.

OBJECTIVE: To examine whether mood symptoms increased more for women in the years after hysterectomy with or without bilateral oophorectomy relative to natural menopause. METHODS: Using data from the Study of Women's Health Across the Nation (n=1,970), depression and anxiety symptoms were assessed annually for up to 10 years with the Center for Epidemiological Studies Depression Index and four anxiety questions, respectively. Piece-wise hierarchical growth models were used to relate natural menopause, hysterectomy with ovarian conservation, and hysterectomy with bilateral oophorectomy to trajectories of mood symptoms before and after the final menstrual period or surgery. Covariates included educational attainment, race, menopausal status, age the year before final menstrual period or surgery, and time-varying body mass index, self-rated health, hormone therapy, and antidepressant use. RESULTS: By the tenth annual visit, 1,793 (90.9%) women reached natural menopause, 76 (3.9%) reported hysterectomy with ovarian conservation, and 101 (5.2%) reported hysterectomy with bilateral oophorectomy. For all women, depressive and anxiety symptoms decreased in the years after final menstrual period or surgery. These trajectories did not significantly differ by hysterectomy or oophorectomy status. The Center for Epidemiological Studies Depression Index means were 0.72 standard deviations lower and anxiety symptoms were 0.67 standard deviations lower 5 years after final menstrual period or surgery. CONCLUSION: In this study, mood symptoms continued to improve after the final menstrual period or hysterectomy for all women. Women who undergo a hysterectomy with or without bilateral oophorectomy in midlife do not experience more negative mood symptoms in the years after surgery. LEVEL OF EVIDENCE: II.

Relative contributions of oligomenorrhea and hyperandrogenemia to the risk of metabolic syndrome in midlife women.

CONTEXT: Young reproductive-age women with irregular menses and androgen excess are at high risk for unfavorable metabolic profile; however, recent data suggest that menstrual regularity and hyperandrogenism improve with aging in affected women approaching menopause. OBJECTIVE: The objective of the study was to determine whether women with hyperandrogenemia (HA) and a history of oligomenorrhea (Oligo) are at an elevated risk for metabolic syndrome (MetS) at the early stages of menopausal transition. METHODS: Baseline data from 2543 participants (mean age of 45.8 yr) in the Study of Women's Health Across the Nation were analyzed. Women with a lifetime history of more than one 3-month interval of nongestational and nonlactational amenorrhea were classified as having a history of Oligo. The highest tertile of serum testosterone was used to define HA. Women with normal serum androgens and eumenorrhea were used as the reference group. Logistic regression models generated adjusted odds ratios (AOR), controlling for age, ethnicity, body mass index, smoking, and study site. RESULTS: Oligo was associated with MetS only when coincident with HA [AOR of 1.93 for Oligo and HA [95% confidence interval (CI) 1.17-3.17], AOR of 1.25 for Oligo and normal androgens (95% CI 0.81-1.93)]. In contrast, HA conferred a consistently significant risk for MetS, regardless of the menstrual frequency status [AOR of 1.48 for HA and eumenorrhea (95% CI 1.15-1.90)]. CONCLUSIONS: Our results suggest that HA but not history of Oligo is independently associated with the risk of prevalent MetS in pre- and perimenopausal women in their 40s.

Association of blood lead concentrations with mortality in older women: a prospective cohort study.

BACKGROUND: Blood lead concentrations have been associated with increased risk of cardiovascular, cancer, and all-cause mortality in adults in general population and occupational cohorts. We aimed to determine the association between blood lead, all cause and cause specific mortality in elderly, community residing women. METHODS: Prospective cohort study of 533 women aged 65-87 years enrolled in the Study of Osteoporotic Fractures at 2 US research centers (Baltimore, MD; Monongahela Valley, PA) from 1986-1988. Blood lead concentrations were determined by atomic absorption spectrometry. Using blood lead concentration categorized as < 8 microg/dL (0.384 micromol/L), and > or = 8 microg/dL (0.384 micromol/L), we determined the relative risk of mortality from all cause, and cause-specific mortality, through Cox proportional hazards regression analysis. RESULTS: Mean blood lead concentration was 5.3 +/- 2.3 microg/dL (range 1-21) [0.25 +/- 0.11 micromol/L (range 0.05-1.008)]. After 12.0 +/- 3 years of > 95% complete follow-up, 123 (23%) women who died had slightly higher mean (+/- SD) blood lead 5.56 (+/- 3) microg/dL [0.27(+/- 0.14) micromol/L] than survivors: 5.17(+/- 2.0) [0.25(+/- 0.1) micromol/L] (p = 0.09). Women with blood lead concentrations > or = 8 microg/dL (0.384 micromol/L), had 59% increased risk of multivariate adjusted all cause mortality (Hazard Ratio [HR], 1.59; 95% confidence interval [CI], 1.02-2.49) (p = 0.041) especially coronary heart disease (CHD) mortality (HR = 3.08 [CI], (1.23-7.70)(p = 0.016), compared to women with blood lead concentrations < 8 microg/dL(< 0.384 mumol/L). There was no association of blood lead with stroke, cancer, or non cardiovascular deaths. CONCLUSION: Women with blood lead concentrations of > or = 8 microg/dL (0.384 micromol/L), experienced increased mortality, in particular from CHD as compared to those with lower blood lead concentrations.

Association of cumulative lead and neurocognitive function in an occupational cohort.

Lead is a neurotoxicant that accumulates in bone with a half life of 25-30 years. To evaluate the association of lead biomarkers and cognitive function, a cohort of exposed and nonexposed workers who had been previously assessed in 1982 was retested approximately 22 years later. For the current assessment, both blood lead and tibia bone lead levels were determined. In addition, cognitive function was tested with the Pittsburgh Occupational Exposures Test battery, which had previously been administered in 1982. In exposed workers, bone lead level predicted lower current cognitive performance and cognitive decline over 22 years. In those lead-exposed workers older than age 55, higher levels of bone lead predicted poorer cognitive scores, suggesting vulnerability for older workers with higher past lead exposure. Finally, there was no association with bone lead level and recency of exposure, suggesting that cumulative body burden is most likely responsible for the progressive cognitive decrement evidenced with vulnerability because of aging.

Relationship of blood lead levels to incident nonspine fractures and falls in older women: the study of osteoporotic fractures.

Lead is stored in the skeleton and can serve as an endogenous source for many years. Lead may influence the risk of fracture, through direct effects on bone strength or indirectly by disturbing neuromuscular function and increasing the risk of falls. The objective of this analysis is to test the hypothesis that women with higher blood lead levels experience higher rates of falls and fracture. This was a prospective cohort study of 533 women 65-87 yr of age enrolled in the Study of Osteoporotic Fractures at two U.S. research centers (Baltimore, MD; Monongahela Valley, PA) from 1986 to 1988. Blood lead levels (in microg/dl) were measured in 1990-1991 by atomic absorption spectrophotometry and classified as "low" (or=8; upper 15th percentile). Total hip BMD was measured by DXA twice, 3.55 yr apart. Information on falls was collected every 4 mo for 4 yr. Incident nonspine fractures were identified and confirmed over 10 yr. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% CI of fracture. Generalized estimating equations were used to calculate the incident rate ratio of falls (95% CI). The mean blood lead level was 5.3 +/- 2.3 (SD) microg/dl (range, 1-21 microg/dl). Baseline BMD was 7% lower in total hip and 5% lower in femoral neck in the highest compared with lowest blood lead group (p < 0.02). Hip bone loss tended to be greater in the high lead group, but differences were not significant. In multivariable adjusted models, women with high blood lead levels had an increased risk of nonspine fracture (HR = 2.50; 95% CI = 1.25, 5.03; p trend = 0.016) and higher risk of falls (incident rate ratio = 1.62; 95% CI = 1.07, 2.45; p trend = 0.014) compared with women with lowest lead level. Blood lead levels are associated with an increased risk of falls and fractures, extending the negative health consequences of lead to include osteoporotic fractures.