Persistent endocrine-disrupting chemicals and incident uterine leiomyomata: A mixtures analysis.

BACKGROUND: Uterine leiomyomata (UL; fibroids) are hormone-dependent neoplasms that can cause significant gynecologic morbidity. Studies have documented associations between concentrations of persistent endocrine-disrupting chemicals (EDCs) and UL incidence; however, few have assessed the effects of EDC mixtures on UL. METHODS: In the Study of Environment, Lifestyle, and Fibroids, a prospective cohort study, participants attended study visits at baseline and approximately every 20 months for up to 10 years; at each visit, they completed questionnaires, provided blood samples, and underwent standardized ultrasound examinations. In baseline plasma samples (n = 1155), we quantified concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides using high-resolution mass spectrometry. We selected nine EDCs detected in >60 % of samples (4 PCBs, 4 PBDEs, and 2,2-bis(4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE)) and conducted probit Bayesian kernel machine regression with hierarchical variable selection to estimate effects of the EDC mixture and individual EDCs on UL incidence, adjusting for potential confounders. RESULTS: During 10 years of follow-up, 32 % of participants developed ultrasound-detected UL. The EDC mixture was not appreciably associated with the probit of UL (ß comparing all EDCs at their 75th vs. 50th percentile:= - 0.01, 95 % credible interval [CrI]: -0.11, 0.10). However, individual EDC concentrations were associated with UL in opposing directions: PCB138/158 was positively associated with UL (ß for 25th-to-75th-percentile increase when all other chemicals were set to their 50th percentile = 0.18, 95 % CrI: -0.09, 0.44), whereas PBDE99 and p,p'-DDE were inversely associated with UL (ß = -0.06, 95 % CrI: -0.21, 0.10 and ß = -0.12, 95 % CrI: -0.34, 0.10, respectively). There was little evidence of interaction between EDCs. CONCLUSION: In this prospective ultrasound study, a mixture of persistent EDCs was not appreciably associated with incident UL during 10 years of follow-up, but individual EDCs were associated with UL in opposite directions.

Associations of per- and polyfluoroalkyl substances with uterine leiomyomata incidence and growth: a prospective ultrasound study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals used in commercial and consumer products. OBJECTIVE: We evaluated PFAS exposure in relation to incidence and growth of uterine leiomyomata (UL), hormone-dependent neoplasms that are associated with severe gynecologic morbidity. METHODS: We studied 1158 participants in the Study of Environment, Lifestyle, and Fibroids, a Detroit-based prospective cohort study of Black females aged 23-35 years at enrollment (2010-2012). At enrollment and four subsequent visits during 10 years of follow-up, participants attended in-person clinic visits, completed questionnaires, provided non-fasting blood samples, and underwent ultrasound for UL detection. We quantified 7 PFAS in baseline plasma samples using mass spectrometry. We used Cox regression and probit Bayesian kernel machine regression to estimate individual and joint effects of PFAS on UL incidence. We fit linear mixed models to estimate effects of individual PFAS on UL growth. We stratified by parity, an important route of PFAS elimination and determinant of UL. RESULTS: In individual PFAS analyses, we observed inverse associations for perfluorodecanoate (PFDA; ≥0.3 vs. <0.2 ng/ml: hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.54-1.00) and perfluoroundecanoate (detected vs. non-detected: HR = 0.78; 95% CI: 0.61-1.01) and a weak positive association for perfluorohexane sulfonate (≥1 vs. <0.6 ng/ml: HR = 1.17; 95% CI: 0.85-1.61), while perfluorooctane sulfonate, perfluorooctanoate, perfluorononanoate (PFNA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA) showed little association with UL incidence. The PFAS mixture was inversely associated with UL incidence, a finding driven by MeFOSAA and PFDA; however, PFNA was positively associated with UL incidence. The inverse association for PFDA and positive association for PFNA were stronger among nulliparous participants. Most PFAS showed slight inverse associations with UL growth. IMPACT STATEMENT: In this prospective ultrasound study of 1158 Black females aged 23-35 years at enrollment, we conducted a mixtures analysis to account for co-pollutant confounding and interaction. MeFOSAA and PFDA concentrations were inversely associated with UL incidence, while PFNA concentrations were positively associated with UL incidence. Concentrations of most PFAS were associated with decreased UL growth. This study contributes data to the sparse literature on PFAS exposure and UL development.

A Prospective Cohort Study of Persistent Endocrine Disrupting Chemicals and Perceived Stress.

Persistent endocrine disrupting chemicals (EDCs) can dysregulate the stress response. We evaluated associations between persistent EDCs and perceived stress among participants from the Study of Environment, Lifestyle and Fibroids (n=1,394), a prospective cohort study of Black women. Participants completed the Perceived Stress Scale (PSS-4) at baseline, and every 20 months through 60 months (range of scores: 0-16); higher scores indicated higher stress. EDCs, including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides, were quantified in plasma samples at baseline. We fit Bayesian Kernel Machine Regression (BKMR) and linear mixed effects models to estimate associations of EDCs (as a mixture and individually) with PSS-4 scores at baseline and at each follow-up visit, respectively. Increasing percentiles of the mixture were not strongly associated with PSS-4 scores at baseline, and no interactions were observed among EDCs. Several individual EDCs (e.g., PFDA, PCB 118, PBDE 99) were associated with higher PSS-4 scores at baseline or follow-up, while other EDCs (e.g., PCB 138/158) were associated with lower PSS-4 scores at baseline or follow-up. The directionality of associations for individual EDCs was inconsistent across follow-up visits. In conclusion, specific EDCs may be associated with perceived stress in Black women.

Hair product use and urinary biomarker concentrations of non-persistent endocrine disrupting chemicals among reproductive-aged Black women.

BACKGROUND: Studies have shown an association between hair product use and adverse health outcomes. Scientists have hypothesized that exposure to endocrine-disrupting chemicals (EDCs) drives these associations, but few studies have directly evaluated associations between hair product use and biomarkers of EDCs. Even more limited are studies of Black women, who frequently use EDC-containing products (e.g., hair relaxers). OBJECTIVE: We estimated associations between hair product use and EDC biomarker concentrations. METHODS: We leveraged cross-sectional data from the Study of Environment, Lifestyle, and Fibroids, a cohort of females aged 23-34 years who self-identified as Black/African American from the Detroit-metropolitan area (USA; n = 425). On structured questionnaires, participants reported their past 24-h and past 12-month use of hair products, including relaxers/straighteners/perms, styling products, moisturizers, oils, and hair food. We quantified urinary concentrations of 19 phthalate/phthalate alternative metabolites, 7 phenols, and 4 parabens using high performance liquid chromatography isotope dilution tandem mass spectrometry. EDC biomarker concentrations were creatinine-adjusted and natural log-transformed. We used multivariable linear regression to estimate mean percent differences in EDC biomarker concentrations and 95% confidence intervals (CIs) associated with hair product use, adjusting for sociodemographic confounders. RESULTS: Hair product use was associated with greater concentrations of multiple EDC biomarkers. Notably, use of hair products in the previous 24 h (compared with non-use) was associated with 16.2% (95% CI = 0.7%, 35.9%), 35.0% (95% CI = 2.6%, 77.6%), and 32.3% (95% CI = 8.8%, 92.0%) higher concentrations of mono-isobutyl phthalate, methyl paraben, and ethyl paraben, respectively. Use of hair relaxers/straighteners/perms, styling products, moisturizers, oils, and hair food in the past 12 months was also associated with higher concentrations of multiple phthalate, phenol, and paraben biomarkers. CONCLUSION: Hair product use was associated with higher biomarker concentrations of multiple phthalates, phenols, and parabens. These findings suggest that hair products are potentially important exposure sources for hormonally-active chemicals among Black women.

Non-persistent endocrine disrupting chemical mixtures and uterine leiomyomata in the study of environment, lifestyle and fibroids (SELF).

BACKGROUND: Results of studies investigating associations between individual endocrine-disrupting chemicals (EDCs) and incidence of uterine leiomyomata (UL), a hormone-dependent gynecological condition, have been inconsistent. However, few studies have evaluated simultaneous exposure to a mixture of EDCs with UL incidence. METHODS: We conducted a case-cohort analysis (n = 708) of data from the Study of the Environment, Lifestyle and Fibroids (SELF), a prospective cohort study. Participants were aged 23-35 years at enrollment, had an intact uterus, and identified as Black or African American. We measured biomarker concentrations of 21 non-persistent EDCs, including phthalates, phenols, parabens, and triclocarban, in urine collected at baseline, 20-month, and 40-month clinic visits. We ascertained UL incidence and characteristics using ultrasounds at baseline and approximately every 20 months through 60 months. We used probit Bayesian Kernel Machine Regression (BKMR-P) to evaluate joint associations between EDC mixtures with cumulative UL incidence. We estimated the mean difference in the probit of UL incidence over the study period, adjusting for baseline age, education, years since last birth, parity, smoking status and body mass index. We converted probit estimates to odds ratios for ease of interpretation. RESULTS: We observed that urinary concentrations of the overall EDC mixture were inversely associated with UL incidence in the overall mixtures model, with the strongest inverse associations at the 70th percentile of all biomarkers compared with their 50th percentile (odds ratio = 0.59; 95% confidence interval: 0.36, 0.96). Strongest contributors to the joint association for the mixture were bisphenol S (BPS), ethyl paraben (EPB), bisphenol F (BPF) and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), which each demonstrated inverse associations except for MECPP. There was suggestive evidence of an interaction between MECPP and EPB. CONCLUSION: In this prospective ultrasound study, we observed evidence of an inverse association between the overall mixture of urinary biomarker concentrations of non-persistent EDCs with UL incidence.

Per- and polyfluoroalkyl substances (PFAS), perceived stress, and depressive symptoms in a prospective cohort study of black women.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals with neurotoxic properties. PFAS have been associated with depressive symptoms among women in some studies, but little research has evaluated the effects of PFAS mixtures. Further, no study has investigated interactions of PFAS-depression associations by perceived stress, which has been shown to modify the effects of PFAS on other health outcomes. OBJECTIVE: In a prospective cohort study of reproductive-aged Black women, we investigated associations between PFAS and depressive symptoms and the extent to which perceived stress modified these associations. METHODS: We analyzed data from 1499 participants (23-35 years) in the Study of Environment, Lifestyle, and Fibroids. We quantified concentrations of nine PFAS in baseline plasma samples using online solid-phase extraction-liquid chromatography-isotope dilution tandem mass spectrometry. Participants reported perceived stress via the Perceived Stress Scale (PSS-4; range = 0-16) at baseline and depressive symptoms via the Center for Epidemiologic Studies Depression Scale (CESD; range = 0-44) at the 20-month follow-up visit. We used Bayesian Kernel Machine Regression to estimate associations between PFAS concentrations, individually and as a mixture, and depressive symptoms, and to assess effect modification by PSS-4 scores, adjusting for confounders. RESULTS: Baseline perfluorodecanoic acid concentrations were associated with greater depressive symptoms at the 20-month follow-up, but associations for other PFAS were null. The PFAS were not associated with depressive symptoms when evaluated as a mixture. The association between the 90th percentile (vs. 50th percentile) of the PFAS mixture with CES-D scores was null at the 10th (ß = 0.03; 95 % CrI = 0.20, 0.25), 50th (ß = 0.02; 95 % CrI = -0.16, 0.19), and 90th (ß = 0.01; 95 % CrI = 0.18, 0.20) percentiles of PSS-4 scores, suggesting perceived stress did not modify the PFAS mixture. CONCLUSION: In this prospective cohort study, PFAS concentrations-assessed individually or as a mixture-were not appreciably associated with depressive symptoms, and there was no evidence of effect modification by perceived stress.

Uterine Fibroids.

This JAMA Insights in the Women's Health series discusses the incidence, diagnosis, and treatment of uterine fibroids.

Identifying individual social needs during intake for diabetes Self-Management education and support services in the Detroit, Michigan area.

The American Diabetes Association has recommended that diabetes self-management education and support (DSMES) teams improve diabetes outcomes by identifying and responding to patients' social needs. This study examines demographic patterns in how hemoglobin A1c (A1c) is related to individual social needs, reported urgency of those needs, and interest in obtaining assistance. A total of 1125 unique persons who had been referred for DSMES and had completed a social needs screener via our electronic medical record were included. The majority (51.9 %) had an A1c < 8 % at their most recent assessment and most respondents (52.5 %) reported having at least 1 unmet social need (n = 591), Those who reported having at least 1 social need, tended to have higher A1c levels compared with those who reported no social needs (median of 8.0 % versus 7.7 %; p < 0.05). Among Black individuals the associations were stronger (median A1c of 8.2 % among those with versus 7.2 % among those without a reported social need; p < 0.05). However, among White individuals, there was no difference in A1c between these two groups. Among those who reported a social need, those who also reported they needed assistance (35.7 %) tended to have higher A1c levels than those who did not (median 8.3 % versus 7.8 %; p < 0.10). This relationship did not vary by race. Ongoing study of the relationship between unmet social needs and glycemic control is warranted to help identify effective clinical workflows to help providers incorporate consideration of social needs into their medical decision making.

Body Mass Index and Uterine Fibroid Development: A Prospective Study.

OBJECTIVE: Fibroids are hormonally dependent uterine tumors. The literature on adiposity and fibroid prevalence is inconsistent. Previous work usually combined all those with body mass indexes (BMIs) ≥30kg/m2 into a single category and relied on clinically diagnosed fibroids which misclassifies the many women with undiagnosed fibroids. We used a prospective cohort design with periodic ultrasound screening to investigate associations between repeated measures of BMI and fibroid incidence and growth assessed at each follow-up ultrasound. METHODS: The Study of Environment, Lifestyle & Fibroids (SELF) followed 1,693 Black/African American women, ages 23-35 from Detroit, Michigan with ultrasound every 20 months for 5 years. Measured height and repeated weight measures were used to calculate BMI. Fibroid incidence was modeled using Cox models among those who were fibroid-free at the enrollment ultrasound. Fibroid growth was estimated for individual fibroids matched across visits as the difference in log-volume between visits and was modeled using linear mixed models. All models used time-varying BMI and adjusted for time-varying covariates. RESULTS: Compared to BMI <25kg/m2 those with BMI 30-<35kg/m2 had increased fibroid incidence (adjusted hazard ratio (aHR) 1.37, (95% Confidence Interval (CI): 0.96-1.94)), those with BMI ≥40kg/m2 had reduced incidence (aHR 0.61, (95% CI: 0.41-0.90)). Fibroid growth had mostly small magnitude associations with BMI. CONCLUSION: BMI has a non-linear association with fibroid incidence that could be driven by effects of BMI on inflammation and reproductive hormones. More detailed measures of visceral and subcutaneous adiposity and their effects on hormones, DNA damage, and cell death are needed.