Phthalates and sex steroid hormones across the perimenopausal period: A longitudinal analysis of the Midlife Women's Health Study.

BACKGROUND: The menopausal transition involves significant sex hormone changes. Environmental chemicals, such as urinary phthalate metabolites, are associated with sex hormone levels in cross-sectional studies. Few studies have assessed longitudinal associations between urinary phthalate metabolite concentrations and sex hormone levels during menopausal transition. METHODS: Pre- and perimenopausal women from the Midlife Women's Health Study (MWHS) (n = 751) contributed data at up to 4 annual study visits. We quantified 9 individual urinary phthalate metabolites and 5 summary measures (e.g., phthalates in plastics (∑Plastic)), using pooled annual urine samples. We measured serum estradiol, testosterone, and progesterone collected at each study visit, unrelated to menstrual cycling. Linear mixed-effects models and hierarchical Bayesian kernel machine regression analyses evaluated adjusted associations between individual and phthalate mixtures with sex steroid hormones longitudinally. RESULTS: We observed associations between increased concentrations of certain phthalate metabolites and lower testosterone and higher sub-ovulatory progesterone levels, e.g., doubling of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), di-2-ethylhexyl phthalate (∑DEHP) metabolites, ∑Plastic, and ∑Phthalates concentrations were associated with lower testosterone (e.g., for ∑DEHP: -4.51%; 95% CI: -6.72%, -2.26%). For each doubling of MEP, certain DEHP metabolites, and summary measures, we observed higher mean sub-ovulatory progesterone (e.g., ∑AA (metabolites with anti-androgenic activity): 6.88%; 95% CI: 1.94%, 12.1%). Higher levels of the overall time-varying phthalate mixture were associated with lower estradiol and higher progesterone levels, especially for 2nd year exposures. CONCLUSIONS: Phthalates were longitudinally associated with sex hormone levels during the menopausal transition. Future research should assess such associations and potential health impacts during this understudied period.

First trimester plasma PER- AND Polyfluoroalkyl Substances (PFAS) and blood pressure trajectories across the second and third trimesters of pregnancy

BACKGROUND: Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases risk of high blood pressure (BP) during pregnancy. Prior studies did not examine associations with BP trajectory parameters (i.e., overall magnitude and velocity) during pregnancy, which is linked to adverse pregnancy outcomes. OBJECTIVES: To estimate associations of multiple plasma PFAS in early pregnancy with BP trajectory parameters across the second and third trimesters. To assess potential effect modification by maternal age and parity. METHODS: In 1297 individuals, we quantified six PFAS in plasma collected during early pregnancy (median gestational age: 9.4 weeks). We abstracted from medical records systolic BP (SBP) and diastolic BP (DBP) measurements, recorded from 12 weeks gestation until delivery. BP trajectory parameters were estimated via Super Imposition by Translation and Rotation modeling. Subsequently, Bayesian Kernel Machine Regression (BKMR) was employed to estimate individual and joint associations of PFAS concentrations with trajectory parameters - adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index, income, parity, smoking status, and seafood intake. We evaluated effect modification by age at enrollment and parity. RESULTS: We collected a median of 13 BP measurements per participant. In BKMR, higher concentration of perfluorooctane sulfonate (PFOS) was independently associated with higher magnitude of overall SBP and DBP trajectories (i.e., upward shift of trajectories) and faster SBP trajectory velocity, holding all other PFAS at their medians. In stratified BKMR analyses, participants with ≥ 1 live birth had more pronounced positive associations between PFOS and SBP velocity, DBP magnitude, and DBP velocity - compared to nulliparous participants. We did not observe significant associations between concentrations of the overall PFAS mixture and either magnitude or velocity of the BP trajectories. CONCLUSION: Early pregnancy plasma PFOS concentrations were associated with altered BP trajectory in pregnancy, which may impact future cardiovascular health of the mother.

Urinary phthalate metabolite concentrations and hot flash outcomes: Longitudinal associations in the Midlife Women's Health Study.

Midlife in women is an understudied time for environmental chemical exposures and menopausal outcomes. Recent cross-sectional research links phthalates with hot flashes, but little is known regarding such associations over time. Our objective was to estimate longitudinal associations between repeated measures of urinary phthalate metabolite concentrations and hot flash outcomes in midlife women. Using data from the Midlife Women's Health Study (MWHS), a prospective longitudinal study, we fit generalized linear mixed-effects models (GLMMs) and Cox proportional hazards regression models to repeated measures over a 4-year period. Recruitment occurred in Baltimore and surrounding counties, Maryland, USA between 2006 and 2015. Participants were premenopausal/perimenopausal women (n = 744) aged 45-54 years, who were not pregnant, not taking menopausal symptom medication or oral contraceptives, did not have hysterectomy/oophorectomy, and irrespective of hot flash experience. Baseline mean (SD) age was 48.4 (2.45), and 65% were premenopausal. Main outcome measures included adjusted odds ratios (ORs) for 4 self-reported hot flash outcomes (ever experienced, past 30 days experience, weekly/daily, and moderate/severe), and hazard ratios (HRs) for incident hot flashes. We observed mostly increased odds of certain hot flash outcomes with higher concentrations of metabolites of di (2-ethylhexyl) phthalate (DEHP), monoisobutyl phthalate (MiBP), and a molar summary measure of plasticizer phthalate metabolites (DEHP metabolites, mono-(3-carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP)). Some associations between exposures and outcomes indicated decreased odds. In conclusion, phthalate metabolites were associated with certain hot flash outcomes in midlife women. Midlife may be a sensitive period for higher phthalate metabolite concentrations with respect to menopausal symptoms.

Preconception Stress and Pregnancy Serum Glucose Levels Among Women Attending a Fertility Center.

Context: The association between women's stress and pregnancy glucose levels remain unclear, specifically when considering the preconception period as a sensitive window of exposure. Objective: We investigated whether preconception perceived stress was associated with glucose levels during pregnancy among women attending a fertility center (2004-2019). Methods: Before conception, women completed a psychological stress survey using the short version of the validated Perceived Stress Scale 4 (PSS-4), and blood glucose was measured using a 50-gram glucose load test during late pregnancy as a part of screening for gestational diabetes. Linear and log-binomial regression models were used to assess associations of total PSS-4 scores with mean glucose levels and abnormal glucose levels ( ≥ 140 mg/dL), adjusting for age, body mass index, race, smoking, education, physical activity, primary infertility diagnosis, number of babies, and mode of conception. Results: Psychological stress was positively associated with mean abnormal glucose levels. The adjusted marginal means (95% CI) of mean glucose levels for women in the first, second, and third tertiles of psychological stress were 115 (110, 119), 119 (115, 123), and 124 (119, 128), and mg/dL, respectively (P for trend = .007). Also, women in the second and third tertiles of psychological stress had 4% and 13% higher probabilities of having abnormal glucose compared with women in the first tertile of psychological stress (P trend = .01). Conclusion: These results highlight the importance of considering preconception when evaluating the relationship between women's stress and pregnancy glucose levels.

Urinary polycyclic aromatic hydrocarbon excretion and regional body fat distribution: evidence from the U.S. National Health and Nutrition Examination Survey 2001-2016.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that may contribute to the etiology of obesity. However, it is unclear whether PAHs from environmental sources are associated with regional body fat distribution, and whether the association varies across racial/ethnic groups who may have differential PAH exposure patterns. OBJECTIVES: To examine correlations between PAHs and body fat distribution, and potential racial/ethnic differences among U.S. adults. METHODS: Ten PAHs were measured in spot urine samples from 2691 non-smoking adults (age ≥ 20 years) in the NHANES 2001-2016. Dual-energy X-ray absorptiometry was used to measure fat mass percent (FM%). Partial Pearson correlation coefficients (r) with multivariable adjustment were used to assess PAH-FM% associations. RESULTS: In the total population, 1-naphthalene, 3-fluorene, and 1-pyrene were inversely correlated with total FM% or trunk FM% (adjusted r ranged: - 0.06 to - 0.08), while 2-naphthalene, 9-fluorene, and 4-phenanthrene were positively correlated with the FM% measurements (r: 0.07-0.11). PAH levels are highest among non-Hispanic Blacks, followed by Hispanics and Whites and some of the correlations were different by these races/ethnicities. Among non-Hispanic Whites, no PAH was correlated with FM%. In contrast, 9-fluorene was positively correlated with total FM% (r = 0.20) and trunk FM% (r = 0.22) among Blacks, and 4-phenanthrene was positively correlated with total FM% (r = 0.23) and trunk FM% (r = 0.24) among Hispanics (P-interaction: 0.010-0.025). DISCUSSION: In this US adult population, certain PAHs are significantly associated with higher body fat contents among non-Hispanic Blacks and Hispanics but not non-Hispanic Whites, suggesting that minority groups might be particularly susceptible to PAH's obesogenic effects or the effects of other factors that determine the PAH exposure levels. Alternatively, differences in body composition may contribute to differential PAH metabolism in minority groups. Future studies are warranted to explore the racial/ethnic disparity in PAH exposures, drivers of these exposure differences, and mechanisms through which PAHs may influence body composition by races/ethnicities.

Hormonal activity in commonly used Black hair care products: evaluating hormone disruption as a plausible contribution to health disparities.

BACKGROUND: Certain types of hair products are more commonly used by Black women. Studies show hair products contain several endocrine-disrupting chemicals that are associated with adverse health outcomes. As chemical mixtures of endocrine disruptors, hair products may be hormonally active, but this remains unclear. OBJECTIVE: To assess the hormonal activity of commonly used Black hair products. METHODS: We identified six commonly used hair products (used by >10% of the population) from the Greater New York Hair Products Study. We used reporter gene assays (RGAs) incorporating natural steroid receptors to evaluate estrogenic, androgenic, progestogenic, and glucocorticoid hormonal bioactivity employing an extraction method using bond elution prior to RGA assessment at dilutions from 50 to 500. RESULTS: All products displayed hormonal activity, varying in the amount and effect. Three samples showed estrogen agonist properties at levels from 12.5 to 20 ng/g estradiol equivalent concentrations All but one sample showed androgen antagonist properties at levels from 20 to 25 ng/g androgen equivalent concentrations. Four samples showed antagonistic and agonistic properties to progesterone and glucocorticoid. SIGNIFICANCE: Hair products commonly used by Black women showed hormonal activity. Given their frequent use, exposure to hormonally active products could have implications for health outcomes and contribute to reproductive and metabolic health disparities.

Assessing Indoor Dust Interference with Human Nuclear Hormone Receptors in Cell-Based Luciferase Reporter Assays.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS), organophosphate esters (OPEs), and polybrominated diphenyl ethers (PBDEs) are hormone-disrupting chemicals that migrate from building materials into air and dust. OBJECTIVES: We aimed to quantify the hormonal activities of 46 dust samples and identify chemicals driving the observed activities. METHODS: We evaluated associations between hormonal activities of extracted dust in five cell-based luciferase reporter assays and dust concentrations of 42 measured PFAS, OPEs, and PBDEs, transformed as either raw or potency-weighted concentrations based on Tox21 high-throughput screening data. RESULTS: All dust samples were hormonally active, showing antagonistic activity toward peroxisome proliferator-activated receptor (PPARγ2) (100%; 46 of 46 samples), thyroid hormone receptor (TRß) (89%; 41 samples), and androgen receptor (AR) (87%; 40 samples); agonist activity on estrogen receptor (ERα) (96%; 44 samples); and binding competition with thyroxine (T4) on serum transporter transthyretin (TTR) (98%; 45 samples). Effects were observed with as little as 4µg of extracted dust. In regression models for each chemical class, interquartile range increases in potency-weighted or unknown-potency chemical concentrations were associated with higher hormonal activities of dust extracts (potency-weighted: ΣPFAS-TRß, ↑28%, p<0.05; ΣOPEs-TRß, ↑27%, p=0.08; ΣPBDEs-TRß, ↑20%, p<0.05; ΣPBDEs-ERα, ↑7.7%, p=0.08; unknown-potency: ΣOPEs-TTR, ↑34%, p<0.05; ΣOPEs-AR, ↑13%, p=0.06), adjusted for chemicals with active, inactive, and unknown Tox21 designations. DISCUSSION: All indoor dust samples exhibited hormonal activities, which were associated with PFAS, PBDE, and OPE levels. Reporter gene cell-based assays are relatively inexpensive, health-relevant evaluations of toxic loads of chemical mixtures that building occupants are exposed to. https://doi.org/10.1289/EHP8054.

Per- and polyfluoroalkyl substance plasma concentrations and metabolomic markers of type 2 diabetes in the Diabetes Prevention Program trial.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widely used chemicals, some of which have been linked to type 2 diabetes. We tested whether PFAS concentrations were cross-sectionally associated with metabolites previously shown to predict incident type 2 diabetes using the Diabetes Prevention Program (DPP), a trial of individuals at high risk of type 2 diabetes. METHODS: We evaluated 691 participants enrolled in the DPP with baseline measures of 10 PFAS (including total perfluorooctanesulfonic acid (PFOS), total perfluorooctanoic acid (PFOA), and Sb-PFOA [branched isomers of PFOA]) and 77 metabolites. We used log2-transformed PFAS concentrations as exposures and standardized metabolite concentrations as outcomes in linear regression models adjusted for age, sex, race/ethnicity, use of anti-hyperlipidemic or triglyceride-lowering medication, income, years of education, marital status, smoking, and family history of diabetes, with Benjamini-Hochberg linear step-up false discovery rate correction. RESULTS: Sb-PFOA was associated with the largest number of tested metabolites (29 of 77). Each doubling in Sb-PFOA was associated with higher leucine (ß = 0.07 [95%CI: 0.02, 0.11] SD) and lower glycine (-0.08 [95%CI: 0.03, -0.13] SD). Each doubling of either total PFOA or n-PFOA was associated with -0.13 [95%CI: 0.04, -0.22] SD lower glycine. PFOA and Sb-PFOA were positively associated with multiple triacylglycerols and diacylglycerols, and total PFOS, total PFOA, and Sb-PFOA were positively associated with phosphatidylethanolamines. CONCLUSIONS: PFAS concentrations are associated with metabolites linked to type 2 diabetes (particularly amino acid, glycerolipid and glycerophospholipid pathways). Further prospective research is needed to test whether these metabolites mediate associations of PFAS and type 2 diabetes.

Hair Maintenance and Chemical Hair Product Usage as Barriers to Physical Activity in Childhood and Adulthood among African American Women.

Qualitative studies have identified haircare practices as important culturally specific barriers to physical activity (PA) among Black/African American (AA) women, but quantitative investigations are lacking. Using the Study of Environment, Lifestyle and Fibroids data among 1558 Black/AA women, we investigated associations between hair product usage/hair maintenance behaviors and PA during childhood and adulthood. Participants reported childhood and current chemical relaxer and leave-in conditioner use. Self-reported PA included childhood recreational sports participation, leisure-time PA engagement during adulthood, and, at each life stage, minutes of and intensity of PA. Adjusting for socioeconomic and health characteristics, we used Poisson regression with robust variance to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for each PA measure for more vs. less frequent hair product use/hair maintenance. Thirty-four percent reported ≥twice/year chemical relaxer use and 22% reported ≥once/week leave-in conditioner use at age 10 years, and neither were associated with PA at age 10 years. In adulthood, ≥twice/year chemical relaxer users (30%) were less likely (PR = 0.90 [95% CI: 0.79-1.02]) and ≥once/week leave-in conditioner users (24%) were more likely (PR = 1.09 [95% CI: 0.99-1.20]) to report intense PA compared to counterparts reporting rarely/never use. Hair product use/maintenance may influence PA among Black/AA women and impact cardiometabolic health disparities.

Pregnancy Per- and Polyfluoroalkyl Substance Concentrations and Postpartum Health in Project Viva: A Prospective Cohort.

CONTEXT: Per- and polyfluoroalkyl substances (PFAS) are environmental chemicals linked to weight gain and type 2 diabetes. OBJECTIVE: We examined the extent to which PFAS plasma concentrations during pregnancy were associated with postpartum anthropometry and biomarkers. DESIGN, PATIENTS, AND MEASURES: We studied women recruited between 1999 and 2002 in the Project Viva prospective cohort with pregnancy plasma concentrations of PFAS, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and 2-(N-ethyl-perfluorooctane sulfonamide) acetic acid (EtFOSAA). Three-year postpartum anthropometry measurements were available from 786 to 801 women, blood pressure from 761 women, and blood biomarkers from 450 to 454 women. We used multivariable regression to evaluate the association of log2-transformed PFAS with postpartum anthropometry, blood pressure, and blood biomarkers (leptin, adiponectin, sex hormone binding globulin [SHBG], hemoglobin A1c, interleukin-6 [IL-6], C-reactive protein), adjusting for age, prepregnancy body mass index, marital status, race/ethnicity, education, income, smoking, parity, and breastfeeding history. RESULTS: Pregnancy concentrations of certain PFAS were associated with greater adiposity (eg, 0.4 cm [95% confidence interval [95%CI]: -0.1, 0.9] greater waist circumference per doubling in EtFOSAA; 0.2 cm [95%CI: -0.1, 0.5] greater mid-upper arm circumference per doubling in PFOA; 1.2 mm [95%CI: 0.1, 2.2] thicker sum of subscapular and triceps skinfolds per doubling in PFOS) and higher systolic blood pressure (eg, 1.2 mm Hg [95%CI: 0.3, 2.2] per doubling in PFOS) at 3 years postpartum. Higher EtFOSAA concentrations were also associated with 10.8% higher IL-6 (95%CI: 3.3, 18.9) and 6.1% lower SHBG (95%CI: 0.7, 11.2) per doubling. CONCLUSIONS: Pregnancy concentrations of EtFOSAA, PFOS, and PFOA were associated with adverse postpartum cardiometabolic markers.

Chemical/straightening and other hair product usage during childhood, adolescence, and adulthood among African-American women: potential implications for health.

Few studies have characterized life course hair product usage beyond ever/never. We investigated hair product use from childhood to adulthood, usage patterns in adulthood, and socioeconomic status (SES) correlates among African-American (AA) women. Using self-reported data from 1555 AA women enrolled in the Study of Environment, Lifestyle, and Fibroids (2010-2018), we estimated the usage frequency of chemical relaxer/straightener (≥twice/year, once/year, and rarely/never) and leave-in/leave-on conditioner (≥once/week, 1-3 times/month, and rarely/never) during childhood, adolescence, and adulthood. Latent class analysis was used to identify patterns of adulthood usage of multiple hair products. SES was compared across latent classes. With a mean age of 33 ± 3.4 years, most women reported ever using chemical relaxers/straighteners (89%), and use ≥twice/year increased from childhood (9%) to adolescence (73%) but decreased in adulthood (29%). Leave-in/leave-on conditioner use followed the same pattern. Each of three identified latent classes reported frequent styling product use and infrequent relaxer/straightener use. Class One was unlikely to use any other products, Class Two moderately used shampoo and conditioner, and Class Three frequently used multiple product types (e.g., moisturizers and conditioners). Participants in the latter two classes reported higher SES. Ever/never characterization may miss important and distinctive patterns of hair product use, which may vary by SES.

Average and time-specific maternal prenatal inflammatory biomarkers and the risk of labor epidural associated fever.

BACKGROUND: The use of labor epidural analgesia has been associated with intrapartum fever, known as labor epidural associated fever (LEAF). LEAF is most commonly non-infectious in origin and associated with elevated inflammatory cytokines. METHODS: The LIFECODES pregnancy cohort was designed to prospectively collect data to evaluate the association of maternal inflammatory biomarkers with preterm birth in women who delivered between 2007 and 2008 at Brigham and Women's Hospital. Our secondary analysis of the data from the cohort identified 182 women for whom inflammatory biomarkers (i.e. interleukin-10, interleukin-1ß, interleukin-6, tumor necrosis factor-α and C-reactive protein) collected longitudinally over four prenatal visits was available. Maternal temperature and other clinical variables were abstracted from medical records. The primary outcome, the presence of LEAF, was defined as oral temperature ≥ 38°C (≥100.4°F) after epidural analgesia initiation. Multivariable logistic regression estimated the association between inflammatory biomarker concentrations and the odds of developing an intrapartum fever after adjusting for a number of potential confounders. RESULTS: Women who developed LEAF were more likely to have a longer duration of epidural analgesia, whereas women who did not develop LEAF were more likely to have induced labor and positive or unknown Group B Streptococcus colonization status. However, no differences were seen by nulliparity, mode of delivery, white blood cell count at admission, baseline temperature, length of rupture of membranes and number of cervical exams performed during labor. Unadjusted and multivariable logistic regression models did not provide evidence for or exclude an association between individual maternal inflammatory biomarkers and the odds of developing LEAF, regardless of visit time-period. CONCLUSION: The predictive value of maternal inflammatory biomarkers measured during early- and mid-pregnancy for the risk of developing LEAF cannot be excluded.

Preterm Delivery and Maternal Cardiovascular Disease Risk Factors: The Nurses' Health Study II.

Background: Preterm delivery has been linked to future maternal cardiovascular disease (CVD); however, research investigating clinical CVD risk factors is limited. We evaluated whether women who have delivered an infant preterm are at higher risk of developing CVD risk factors after adjustment for prepregnancy confounders. Materials and Methods: We examined the association between preterm delivery and incident chronic hypertension, type 2 diabetes mellitus (T2DM), and hypercholesterolemia among 57,904 parous women in the Nurses' Health Study II. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between preterm delivery in first pregnancy and each CVD risk factor; adjusted cumulative incidence curves were computed using the Breslow estimator. Results: Preterm delivery (<37 weeks) was associated with HRs of 1.11 (95% CI: 1.06-1.17) for chronic hypertension, 1.17 (95% CI: 1.03-1.33) for T2DM, and 1.07 (95% CI: 1.03-1.11) for hypercholesterolemia, adjusting for age, race/ethnicity, parental education, and prepregnancy confounders (e.g., body mass index, smoking, and family history). HRs were higher in women who delivered very preterm (<32 weeks) and in the first 10 years after first birth. The cumulative incidence of each risk factor was highest in women who delivered very preterm. Conclusions: Women with a history of preterm delivery are at higher risk of developing chronic hypertension, T2DM, and hypercholesterolemia in the years after pregnancy. This increased risk was particularly pronounced in the first 10 years after a preterm delivery, indicating that it may be an important time period to implement lifestyle interventions.

Urinary cadmium concentrations and metabolic syndrome in U.S. adults: The National Health and Nutrition Examination Survey 2001-2014.

BACKGROUND: Low to moderate acute cadmium exposure has been associated with increased risk of chronic diseases, such as cardiovascular and kidney disease. Little is known about the association between urinary cadmium levels-an indicator of longer-term exposure-and metabolic syndrome (MetS). METHODS: We analysed data from 3982 participants aged 20-<80 years of the National Health and Nutrition Examination Survey 2001-2014. Urinary cadmium levels were measured and adjusted for creatinine using spot urine samples. Cadmium levels were evaluated in quintiles (Q). MetS was defined by National Cholesterol Education Program's Adult Treatment Panel III report criteria. Prevalence odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression accounting for complex survey design, while adjusting for potential confounders and stratifying by sex and smoking status. RESULTS: In the overall study population, there was a marginal inverse association between urinary cadmium and MetS (adj. OR for Q5 versus Q1: 0.7; 95% CI: 0.5-1.0). Sex stratified models were similar. When examining individual components of MetS, participants with higher levels of urinary cadmium had decreased odds of abdominal obesity (adj. OR for Q5 versus Q1 0.4; 95% CI: 0.3-0.6), but increased odds for low HDL (adj. OR for Q5 versus Q1 2.1; 95% CI: 1.4-3.1). Among current smokers, higher urinary cadmium was associated with increased odds of MetS, hypertension, and low HDL even after accounting for serum cotinine-a marker of smoking intensity. CONCLUSIONS: Higher levels of urinary cadmium, a marker of long term exposure, were not associated with an increased risk of MetS in the overall study population. However, higher urine cadmium was associated with altered MetS components. Current smokers were the most vulnerable group, with higher long-term cadmium exposure being associated with increased risk of MetS, low HDL, and hypertension.

Hair product use, age at menarche and mammographic breast density in multiethnic urban women.

BACKGROUND: Select hair products contain endocrine disrupting chemicals (EDCs) that may affect breast cancer risk. We hypothesize that, if EDCs are related to breast cancer risk, then they may also affect two important breast cancer risk factors: age at menarche and mammographic breast density. METHODS: In two urban female cohorts (N = 248): 1) the New York site of the National Collaborative Perinatal Project and 2) the New York City Multiethnic Breast Cancer Project, we measured childhood and adult use of hair oils, lotions, leave-in conditioners, root stimulators, perms/relaxers, and hair dyes using the same validated questionnaire. We used multivariable relative risk regression models to examine the association between childhood hair product use and early age at menarche (defined as <11 years of age) and multivariable linear regression models to examine the association between childhood and adult hair product use and adult mammographic breast density. RESULTS: Early menarche was associated with ever use of childhood hair products (RR 2.3, 95% CI 1.1, 4.8) and hair oil use (RR 2.5, 95% CI 1.2, 5.2); however, additional adjustment for race/ethnicity, attenuated associations (hair products RR 1.8, 95% CI 0.8, 4.1; hair oil use RR 2.3, 95% CI 1.0, 5.5). Breast density was not associated with adult or childhood hair product or hair oil use. CONCLUSIONS: If confirmed in larger prospective studies, these data suggest that exposure to EDCs through hair products in early life may affect breast cancer risk by altering timing of menarche, and may operate through a mechanism distinct from breast density.

Perinatal weight and risk of prenatal and postpartum depressive symptoms.

PURPOSE: Prepregnancy obesity and weight changes accompanying pregnancy (gestational weight gain and postpartum weight retention) may be associated with risk of maternal depressive symptoms during pregnancy and in the postpartum. The few studies that have examined these relationships report conflicting findings. METHODS: We studied pregnant (n = 2112) and postpartum (n = 1686) women enrolled in Project Viva. We used self-reported prepregnancy and postpartum weight and measured prenatal weight to calculate prepregnancy body mass index (BMI), gestational weight gain (GWG), and postpartum weight retention at 6 months after birth. We assessed elevated depressive symptoms (EDS) with the Edinburgh Postnatal Depression Scale (≥13 on 0-30 scale) at midpregnancy and 6 months postpartum. We used logistic regression to estimate the odds of prenatal and postpartum EDS in relation to prepregnancy BMI, GWG, and postpartum weight retention. RESULTS: A total of 214 (10%) participants experienced prenatal EDS and 151 (9%) postpartum EDS. Neither prepregnancy BMI nor GWG was associated with prenatal EDS. Prepregnancy obesity (BMI ≥ 30 kg per m2) was associated with higher odds of postpartum EDS (odds ratio = 1.69, 95% confidence interval, 1.01-2.83) compared to normal prepregnancy weight in a model adjusted for age, race/ethnicity, nativity, education, marital status, household income, parity, pregnancy intention, and smoking. CONCLUSIONS: Prepregnancy obesity is associated with elevated depressive symptoms in the postpartum period. Given the current obesity epidemic in the US and the consequences of perinatal depression, additional prevention and screening efforts in this population may be warranted.

Racial/ethnic disparities in environmental endocrine disrupting chemicals and women's reproductive health outcomes: epidemiological examples across the life course.

Disparities in women's reproductive health outcomes across the life course have been well-documented. Endocrine disrupting chemicals may be one factor driving disparities, as studies suggest exposure to certain environmental endocrine disrupting chemicals, such as certain phthalates, bisphenol A, parabens and polybrominated diphenyl ethers are higher in non-whites. Yet, a limited amount of research has focused on these chemical exposures as a potential mediator of racial/ethnic differences in women's reproductive health outcomes, such as pubertal development, fibroids, infertility, and pregnancy complications. Given that race/ethnicity is a social construct, the purpose of this review was to present the current state of the literature on racial/ethnic disparities in both environmental endocrine disrupting chemicals, as well as associations between these chemicals and selected women's reproductive health outcomes. Our goal was to evaluate literature from populations based in the United States to: 1) characterize racial/ethnic differences in environmental endocrine disrupting chemicals and 2) systematically review literature on environmental endocrine disrupting chemicals and selected women's health outcomes in populations containing more than one racial/ethnic group. This review highlights the need for future work in determining whether higher exposures to some environmental endocrine disrupting chemicals might partly explain differences in women's reproductive health outcomes in these higher-exposure and high-risk groups.

Short-term insulin requirements following gastric bypass surgery in severely obese women with type 1 diabetes.

BACKGROUND: In severely obese type 2 diabetes patients, gastric bypass surgery (GB) reduces body mass index (BMI) and hemoglobin A1c (HbA1c) and allows reduced doses of insulin and other medications. Data regarding the effects of GB on severely obese patients with type 1 diabetes are limited. METHODS: Severely obese women with type 1 diabetes (n = 9) were studied immediately before and after GB (7.7 ± 5.8 weeks, mean ± SD). RESULTS: On average, GB reduced mean BMI by 11% and mean HbA1c by 0.9% (from 8.0 to 7.1%), with a parallel 38% decrease in basal insulin requirements (expressed per kilogram of body weight). CONCLUSION: GB rapidly decreased BMI, HbA1c, and insulin requirements in severely obese women with type 1 diabetes. However, physiologic insulin replacement remains necessary in patients with type 1 diabetes.

The association of circulating angiogenic factors and HbA1c with the risk of preeclampsia in women with preexisting diabetes.

OBJECTIVE: To assess whether glycemic control, soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF) were associated with the development of preeclampsia (PE) or gestational hypertension (GHTN) in women with preexisting diabetes. METHODS: Maternal circulating angiogenic factors (sFlt1 and PlGF) measured on automated platform were studied at four time points during pregnancy in women with diabetes (N = 159) and reported as multiples of the median (MOM) of sFlt1/PlGF ratio (median, 25th-75th percentile) noted in non-diabetic non-hypertensive control pregnant population (N = 139). Diagnosis of PE or GHTN was determined by review of de-identified clinical data. RESULTS: PE developed in 12% (N = 19) and GHTN developed in 23% (N = 37) of the women with diabetes. Among diabetic women without PE or GHTN, median sFlt1/PlGF levels at 35-40 weeks was threefold higher than in non-diabetic controls [MOM 3.21(1.19-7.24), p = 0.0001]. Diabetic women who subsequently developed PE had even greater alterations in sFlt1/PlGF ratio during the third trimester [MOM for PE at 27-34 weeks 15.18 (2.37-26.86), at 35-40 weeks 8.61(1.20-18.27), p ≤ 0.01 for both windows compared to non-diabetic controls]. Women with diabetes who subsequently developed GHTN also had significant alterations in angiogenic factors during third trimester; however, these findings were less striking. Among women with diabetes, glycosylated hemoglobin (HbA1c) during the first trimester was higher in subjects who subsequently developed PE (7.7 vs 6.7%, p = 0.0001 for diabetic PE vs diabetic non-PE). CONCLUSIONS: Women with diabetes had a markedly altered anti-angiogenic state late in pregnancy that was further exacerbated in subjects who developed PE. Altered angiogenic factors may be one mechanism for the increased risk of PE in this population. Increased HbA1c in the first trimester of pregnancies in women with diabetes was strongly associated with subsequent PE.