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.

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.

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.

Uterine Fibroids.

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

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.

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.

Personal Care Products, Socioeconomic Status, and Endocrine-Disrupting Chemical Mixtures in Black Women.

Personal care products (PCPs) are sources of exposure to endocrine-disrupting chemicals (EDCs) among women, and socioeconomic status (SES) may influence these exposures. Black women have inequitable exposure to EDCs from PCP use, but no study has investigated how exposure to EDCs through PCPs may vary by SES, independent of race. Using data from the Study of Environment, Lifestyle, and Fibroids, a cohort of reproductive-aged Black women (n = 751), we quantified associations between PCPs and urinary biomarker concentrations of EDC mixtures (i.e., phthalates, phenols, parabens) within SES groups, defined using k-modes clustering based on education, income, marital status, and employment. Information about PCP use and SES was collected through questionnaires and interviews. We used principal component analysis to characterize the EDC mixture profiles. Stratified linear regression models were fit to assess associations between PCP use and EDC mixture profiles, quantified as mean differences in PC scores, by SES group. Associations between PCP use and EDC mixture profiles varied by SES group; e.g., vaginal powder use was associated with a mixture of phenols among lower SES women, whereas this association was null for higher SES women. Findings suggest that SES influences PCP EDC exposure in Black women, which has implications for public health interventions.

Racial disparities between measures of area deprivation and financial toxicity, and uterine volume in myomectomy patients.

BACKGROUND: At time of myomectomy, a surgical procedure to remove uterine fibroids, Black women tend to have larger uteri than White women. This makes Black patients less likely to undergo a minimally invasive myomectomy which has been shown to have less postoperative pain, less frequent postoperative fever and shorter length of stay compared to abdominal myomectomies. The associations between individual financial toxicity and community area deprivation and uterine volume at the time of myomectomy have not been investigated. METHODS: We conducted a secondary data analysis of patients with fibroids scheduled for myomectomy using data from a fibroid treatment registry in [location]. We used validated measures of individual-level Financial Toxicity (higher scores = better financial status) and community-level Area Deprivation (ADI, high scores = worse deprivation). To examine associations with log transformed uterine volume, we used linear regression clustered on race (Black vs. White). RESULTS: Black participants had worse financial toxicity, greater deprivation and larger uterine volumes compared with White participants. A greater Financial Toxicity score (better financial status) was associated with lower uterine volume. For every 10 unit increase in Financial Toxicity, the mean total uterine volume decreased by 9.95% (Confidence Interval [CI]: -9.95%, -3.99%). ADI was also associated with uterine volume. A single unit increase in ADI (worse deprivation) was associated with a 5.13% (CI: 2.02%, 7.25%) increase in mean uterine volume. CONCLUSION: Disproportionately worse Financial Toxicity and ADI among Black patients is likely due to structural racism - which now must be considered in gynecologic research and practice. TRIAL REGISTRATION: Not applicable.

Early Life Disadvantage and the Risk of Depressive Symptoms among Young Black Women.

OVERVIEW: We examined the association between early-life socioeconomic disadvantage and depressive symptoms in adulthood and assessed whether social factors in adulthood modify the association. METHODS: The 11-item Center for Epidemiologic Studies-Depression Scale (CES-D) assessed adult depressive symptoms among 1612 Black women and other participants with a uterus (hereafter participants) in the Study of Environment, Lifestyle and Fibroids. Baseline self-reported childhood factors (i.e., parents in the household, mother's educational attainment, food insecurity, neighborhood safety, childhood income, and quiet bedroom for sleep) were included in a latent class analysis to derive an early life disadvantage construct. Multivariable log-binomial models estimated the association between early life disadvantage and adult depressive symptoms. Potential effect modifiers included adult educational attainment, social support, and financial difficulty. RESULTS: Participants classified as having high early life disadvantage had 1.34 times (95% CI: 1.20, 1.49) the risk of high depressive symptoms than those in the low early life disadvantage class after adjusting for age, first born status, and childhood health. Adult educational attainment and social support modified the association. CONCLUSION: Early life disadvantage increased the risk of depressive symptoms in adulthood. Participants with at least some college education and with high social support had greater risk than those with less than college education and low social support, respectively. Thus, the mental health of Black women and other participants with a uterus exposed to early life disadvantage do not necessarily benefit from higher education or from social support.

A prospective ultrasound study of cigarette smoking and uterine leiomyomata incidence and growth.

BACKGROUND: Uterine leiomyomata (fibroids) are common, benign neoplasms that contribute substantially to gynecologic morbidity. Some existing epidemiologic studies indicate that cigarette smoking is associated with lower uterine leiomyomata risk. However, no prospective studies have systematically screened an entire study population for uterine leiomyomata using transvaginal ultrasound or evaluated the association between cigarette smoking and uterine leiomyomata growth. OBJECTIVE: This study aimed to examine the association between cigarette smoking and uterine leiomyomata incidence and growth in a prospective ultrasound study. STUDY DESIGN: We enrolled 1693 residents from the Detroit metropolitan area into the Study of Environment, Lifestyle, and Fibroids during 2010 to 2012. Eligible participants were aged 23 to 34 years, had an intact uterus but no previous diagnosis of uterine leiomyomata, and self-identified as Black or African American. We invited participants to complete a baseline visit and 4 follow-up visits over approximately 10 years. At each visit, we used transvaginal ultrasound to assess uterine leiomyomata incidence and growth. Participants provided extensive self-reported data throughout follow-up including exposures to active and passive cigarette smoking in adulthood. We excluded participants who did not return for any follow-up visits (n=76; 4%). We fit Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals for the association between time-varying smoking history and incidence rates of uterine leiomyomata. We fit linear mixed models to estimate the percentage difference and 95% confidence intervals for the association between smoking history and uterine leiomyomata growth. We adjusted for sociodemographic, lifestyle, and reproductive factors. We interpreted our results based on magnitude and precision rather than binary significance testing. RESULTS: Among 1252 participants without ultrasound evidence of uterine leiomyomata at baseline, uterine leiomyomata were detected in 394 participants (31%) during follow-up. Current cigarette smoking was associated with a lower uterine leiomyomata incidence rate (hazard ratio, 0.67; 95% confidence interval, 0.49-0.92). Associations were stronger among participants who had smoked for longer durations (≥15 years vs never: hazard ratio, 0.49; 95% confidence interval, 0.25-0.95). The hazard ratio for former smokers was 0.78 (95% confidence interval, 0.50-1.20). Among never smokers, the hazard ratio for current passive smoke exposure was 0.84 (95% confidence interval, 0.65-1.07). Uterine leiomyomata growth was not appreciably associated with current (percent difference, -3%; 95% confidence interval, -13% to 8%) or former (percent difference, -9%; 95% confidence interval, -22% to 6%) smoking. CONCLUSION: We provide evidence from a prospective ultrasound study that cigarette smoking is associated with lower uterine leiomyomata incidence.

Long-term health-related quality of life and symptom severity following hysterectomy, myomectomy, or uterine artery embolization for the treatment of symptomatic uterine fibroids.

BACKGROUND: Few studies have directly compared different surgical procedures for uterine fibroids with respect to long-term health-related quality of life outcomes and symptom improvement. OBJECTIVE: We examined differences in change from baseline to 1-, 2-, and 3-year follow-up in health-related quality of life and symptom severity among patients who underwent abdominal myomectomy, laparoscopic or robotic myomectomy, abdominal hysterectomy, laparoscopic or robotic hysterectomy, or uterine artery embolization. STUDY DESIGN: The COMPARE-UF registry is a multiinstitutional prospective observational cohort study of women undergoing treatment for uterine fibroids. A subset of 1384 women aged 31 to 45 years who underwent either abdominal myomectomy (n=237), laparoscopic myomectomy (n=272), abdominal hysterectomy (n=177), laparoscopic hysterectomy (n=522), or uterine artery embolization (n=176) were included in this analysis. We obtained demographics, fibroid history, and symptoms by questionnaires at enrollment and at 1, 2, and 3 years posttreatment. We used the UFS-QoL (Uterine Fibroid Symptom and Quality of Life) questionnaire to ascertain symptom severity and health-related quality of life scores among participants. To account for potential baseline differences across treatment groups, a propensity score model was used to derive overlap weights and compare total health-related quality of life and symptom severity scores after enrollment with a repeated measures model. For this health-related quality of life tool, a specific minimal clinically important difference has not been determined, but on the basis of previous research, a difference of 10 points was considered as a reasonable estimate. Use of this difference was agreed upon by the Steering Committee at the time when the analysis was planned. RESULTS: At baseline, women undergoing hysterectomy and uterine artery embolization reported the lowest health-related quality of life scores and highest symptom severity scores compared with those undergoing abdominal myomectomy or laparoscopic myomectomy (P<.001). Those undergoing hysterectomy and uterine artery embolization reported the longest duration of fibroid symptoms with a mean of 6.3 years (standard deviation, 6.7; P<.001). The most common fibroid symptoms were menorrhagia (75.3%), bulk symptoms (74.2%), and bloating (73.2%). More than half (54.9%) of participants reported anemia, and 9.4% women reported a history of blood transfusion. Across all modalities, total health-related quality of life and symptom severity score markedly improved from baseline to 1-year with the largest improvement in the laparoscopic hysterectomy group (Uterine Fibroids Symptom and Quality of Life: delta= [+] 49.2; symptom severity: delta= [-] 51.3). Those undergoing abdominal myomectomy, laparoscopic myomectomy, and uterine artery embolization also demonstrated significant improvement in health-related quality of life (delta= [+]43.9, [+]32.9, [+]40.7, respectively) and symptom severity (delta= [-]41.4, [-] 31.5, [-] 38.5, respectively) at 1 year, and the improvement persisted from baseline for uterine-sparing procedures during second (Uterine Fibroids Symptom and Quality of Life: delta= [+]40.7, [+]37.4, [+]39.3 SS: delta= [-] 38.5, [-] 32.0, [-] 37.7 and third year (Uterine Fibroids Symptom and Quality of Life: delta= [+] 40.9, [+]39.9, [+]41.1 and SS: delta= [-] 33.9, [-]36.5, [-] 33.0, respectively), posttreatment intervals, however with a trend toward decline in degree of improvement from years 1 and 2. Differences from baseline were greatest for hysterectomy; however, this may reflect the relative importance of bleeding in the Uterine Fibroids Symptom and Quality of Life, rather than clinically meaningful symptom recurrence among women undergoing uterus-sparing treatments. CONCLUSION: All treatment modalities were associated with significant improvements in health-related quality of life and symptom severity reduction 1-year posttreatment. However, abdominal myomectomy, laparoscopic myomectomy and uterine artery embolization indicated a gradual decline in symptom improvement and health-related quality of life by third year after the procedure.

A Comparative Analysis of Health-Related Quality of Life 1 Year Following Myomectomy or Uterine Artery Embolization: Findings from the COMPARE-UF Registry.

Objective: To compare 12-month post-treatment health-related quality of life (HR-QoL) and symptom severity (SS) changes among patients with symptomatic uterine fibroids (SUF) not seeking fertility and undergo a hysterectomy, abdominal myomectomy (AM), or uterine artery embolization (UAE). Materials and Methods: The Comparing Options for Management: Patient-Centered Results for Uterine Fibroids (COMPARE-UF) Registry is a multi-institutional prospective observational cohort study of patients treated for SUF. A subset of 1465 women 31-45 years of age, who underwent either hysterectomy (n = 741), AM (n = 446), or UAE (n = 155) were included in this analysis. Demographics, fibroid history, and symptoms were obtained by baseline questionnaires and at 1 year post-treatment. Results were stratified by all treatments and propensity score weighting to adjust for differences in baseline characteristics. Results: Women undergoing UAE reported the lowest baseline HR-QoL and highest SS scores (mean = 40.6 [standard deviation (SD) = 23.8]; 62.3 [SD = 24.2]) followed by hysterectomy (44.3 [24.3]; 59.8 [SD = 24.1]). At 12 months, women who underwent a hysterectomy experienced the largest change in both HR-QoL (48.7 [26.2]) and SS (51.9 [25.6]) followed by other uterine-sparing treatments. Propensity score weighting revealed all treatments produced substantial improvement, with hysterectomy patients reporting the highest HR-QoL score (92.0 [17.8]) compared with myomectomy (86.7 [17.2]) and UAE (82.6 [21.5]) (p < 0.0001). Similarly, hysterectomy patients reported the lowest SS scores (8.2 [15.1]) compared with myomectomy (16.5 [15.1]) and UAE (19.6 [17.5]) (p < 0.0001). Conclusion: All procedures showed improvement in HR-QoL and reduction in SS score at 12 months, hysterectomy showing maximum improvement. Of importance, at 12 months, patients who underwent either a myomectomy or UAE reported comparable symptom relief and HR-QoL. Clinicaltrials.Gov Identifier: NCT02260752.

Life-Course Mobility in Socioeconomic Position and High Depressive Symptoms Among Young Black Women: The SELF Study.

BACKGROUND: Current literature on the association between mobility in socioeconomic position (SEP) and depression demonstrates mixed findings, with variation in the benefits of upward SEP by racial group and ethnic background. No study has examined life-course SEP mobility and depressive symptoms among Black women in the United States. METHODS: Our cohort included 1,612 Black women enrolled in the Study of Environment, Lifestyle and Fibroids between 2010 and 2012 and followed for 5 years. We used data on socioeconomic indicators at childhood and adulthood and used latent class analysis to create a life-course SEP mobility measure (persistently low, downward, upward, and persistently high). Using the 11-item Center for Epidemiologic Studies Depression Scale (CES-D), we assessed high (≥9) versus low depressive symptoms. Multivariable log risk models were used to produce risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Of the participants, 37% had high depressive symptoms. Persistently low (RR, 1.56; 95% CI, 1.31-1.86) and downward (RR, 1.36; 95% CI, 1.14-1.63) SEP mobility was associated with high depressive symptoms after adjustment for age, adult social support, and marital status. There was evidence of an effect measure modification by adult social support, with a stronger association among those who reported high adult social support compared with low adult social support. CONCLUSIONS: These findings suggest directing mental health resources to people experiencing low SEP at any stage in life, especially those with low SEP in adulthood, to aid in the management of depressive symptoms.

Ultrasound-Confirmed, Age-Specific Uterine Leiomyoma Incidence in a Cohort of Black Individuals.

OBJECTIVE: To estimate the age-specific incidence of uterine leiomyomas identified by transvaginal ultrasonography among participants in SELF (Study of Environment, Lifestyle & Fibroids). METHODS: SELF is a longitudinal cohort study of individuals aged 23-35 years who self-identified as Black. Participants were recruited from the Detroit, Michigan, area and underwent up to five transvaginal ultrasonograms over a period of up to 10 years to identify uterine leiomyomas. We randomly imputed incidence dates between the last ultrasonogram date in which no leiomyomas were detected and the date of the ultrasonogram in which leiomyomas were first detected. We used Poisson regression to estimate age-specific incidence rates per 1,000 person-years with 95% CIs. The rates were then compared with those of the BWHS (Black Women's Health Study) and the NHS II (Nurses' Health Study II)-two prospective cohort studies based on self-reported leiomyoma diagnoses. RESULTS: In this cohort, 1,693 participants completed a baseline interview and ultrasonogram. We excluded 385 (22.7%) participants with leiomyomas detected during baseline, seven participants whose ultrasonograms were poor quality, and 60 participants with only a baseline ultrasonogram. Among the remaining 1,241 participants, the overall incidence rate was 53.9 cases per 1,000 person-years (95% CI 48.6-59.6). The age-specific incidence rates (cases/1,000 person-years) were: younger than 30 years: 49.7, 95% CI 40.9-59.9; 30-34 years: 55.2, 95% CI 47.0-64.3; and 35-39 years: 58.2, 95% CI 47.3-70.9. Among participants aged younger than 30 years, the incidence rate in SELF was more than double that of the BWHS or the NHS II. CONCLUSION: The high age-specific leiomyoma incidence rates in this prospective ultrasound-based study indicate that many young Black individuals with leiomyomas go undiagnosed. These data suggest that individuals could benefit from ultrasound screening when they experience symptoms compatible with leiomyomas (eg, heavy menstrual bleeding, anemia, pelvic pain).

Transcriptome and DNA methylome analyses reveal underlying mechanisms for the racial disparity in uterine fibroids.

Uterine fibroids (leiomyomas) affect Black women disproportionately compared with women of other races and ethnicities in terms of prevalence, incidence, and severity of symptoms. The causes of this racial disparity are essentially unknown. We hypothesized that myometria of Black women are more susceptible to developing fibroids, and we examined the transcriptomic and DNA methylation profiles of myometria and fibroids from Black and White women for comparison. Myometrial samples cluster by race in both their transcriptome and DNA methylation profiles, whereas fibroid samples only cluster by race in the latter. More differentially expressed genes (DEGs) were detected in the Black and White myometrial sample comparison than in the fibroid comparison. Leiomyoma gene set expression analysis identified 4 clusters of DEGs, including a cluster of 24 genes with higher expression in myometrial samples from Black women. One of the DEGs in this group, von Willibrands factor (VWF), was significantly hypomethylated in both myometrial samples from Black women and in all fibroids at 2 CpG probes that are near a putative enhancer site and that are correlated with VWF expression levels. These results suggest that the molecular basis for the disparity in fibroid disease between Black and White women could be found in the myometria before fibroid development and not in the fibroids themselves.

Vitamin D and uterine fibroid growth, incidence, and loss: a prospective ultrasound study.

OBJECTIVE: Fibroid treatments that have few side-effects and can preserve fertility are a clinical priority. We studied the association between serum vitamin D and uterine fibroid growth, incidence, and loss. DESIGN: A prospective community cohort study (enrollment 2010-2012) with 4 study visits over 5 years to conduct standardized ultrasounds, measure 25-hydroxyvitamin D (25(OH)D), and update covariates. SETTING: Detroit, Michigan area. PATIENTS: Self-identified African American or Black women aged 23-35 at enrollment without previous clinical diagnosis of fibroids. INTERVENTION(S): Serum 25(OH)D measured using immunoassay or liquid chromatography-tandem mass spectrometry. MAIN OUTCOME MEASURE(S): The primary outcomes were fibroid growth, as measured by change in log volume per 18 months, and fibroid incidence (first detection of fibroid in previously fibroid-free uterus). Adjusted growth estimates from linear mixed models were converted to estimated difference in volume for high vs. low 25(OH)D. Incidence differences were estimated as hazard ratios from age-specific Cox regression. A secondary outcome fibroid loss (reduction in fibroid number between visits), was modeled using Poisson regression. Covariates (reproductive and hormonal variables, demographics, body mass index, current smoking) and 25(OH)D were modeled as time-varying factors. RESULT(S): At enrollment among 1,610 participants with ≥1 follow-up ultrasound, mean age was 29.2 years, 73% had deficient vitamin D (<20ng/mL), and only 7% had sufficient vitamin D (≥30ng/mL). Serum 25(OH)D ≥20ng/mL compared with <20ng/mL was associated with an estimated 9.7% reduction in fibroid growth (95% confidence interval [CI]: -17.3%, -1.3%), similar to the minimally adjusted estimate -8.4% (95% CI: -16.4, 0.3). Serum 25(OH)D ≥30ng/mL compared with <30ng/mL was associated with an imprecise 22% reduction in incidence (adjusted hazard ratio=0.78; 95% CI: 0.47, 1.30), similar to the unadjusted estimate of 0.84 (95% CI: 0.51, 1.39). The >30ng/mL group also had a 32% increase in fibroid loss (adjusted risk ratio=1.32; 95% CI: 0.95, 1.83). CONCLUSION(S): Our data support the hypothesis that high concentrations of vitamin D decrease fibroid development but are limited by the few participants with serum 25(OH)D ≥30ng/mL. Interventional trials that raise and maintain 25(OH)D concentrations >30ng/mL and then prospectively monitor fibroid development are needed to further assess supplemental vitamin D efficacy and determine optimal treatment protocols.

Correlates of whole blood metal concentrations among reproductive-aged Black women.

BACKGROUND: Metals may influence reproductive health, but few studies have investigated correlates of metal body burden among reproductive-aged women outside of pregnancy. Furthermore, while there is evidence of racial disparities in exposure to metals among U.S. women, there is limited research about correlates of metal body burden among Black women. OBJECTIVE: To identify correlates of whole blood metal concentrations among reproductive-aged Black women. METHODS: We analyzed cross-sectional data from a cohort of 1664 Black women aged 23-35 years in Detroit, Michigan, 2010-2012. We collected blood samples and questionnaire data. We measured concentrations of 17 metals in whole blood using inductively-coupled plasma-mass spectrometer-triple quadrupole and total mercury using Direct Mercury Analyzer-80. We used multivariable linear regression models to identify sociodemographic, environmental, reproductive, and dietary correlates of individual metal concentrations. RESULTS: In adjusted models, age was positively associated with multiple metals, including arsenic, cadmium, and mercury. Education and income were inversely associated with cadmium and lead. Current smoking was strongly, positively associated with cadmium and lead. Alcohol intake in the past year was positively associated with arsenic, barium, copper, lead, mercury, vanadium, and zinc. Having pumped gasoline in the past 24 h was positively associated with cadmium, chromium, and molybdenum. Having lived in an urban area for the majority of residence in Michigan was positively associated with arsenic, lead, and nickel. Higher water intake in the past year was positively associated with several metals, including lead. Fish intake in the past year was positively associated with arsenic, cesium, and mercury. We also observed associations with body mass index, season, and other environmental, reproductive, and dietary factors. SIGNIFICANCE: We identified potential sources of exposure to metals among reproductive-aged Black women. Our findings improve understanding of exposures to metals among non-pregnant reproductive-aged women, and can inform policies in support of reducing disparities in exposures. IMPACT STATEMENT: There are racial disparities in exposures to metals. We analyzed correlates of blood metal concentrations among reproductive-aged Black women in the Detroit, Michigan metropolitan area. We identified sociodemographic, anthropometric, lifestyle, environmental, reproductive, and dietary correlates of metal body burden. Age was positively associated with several metals. Education and income were inversely associated with cadmium and lead, indicating socioeconomic disparities. We identified potential exposure sources of metals among reproductive-aged Black women, including smoking, environmental tobacco smoke, pumping gasoline, living in an urban area, and intake of alcohol, water, fish, and rice.

Route of myomectomy and fertility: a prospective cohort study.

OBJECTIVE: To assess prospectively the association between the myomectomy route and fertility. DESIGN: Prospective cohort study. SETTING: The Comparing Treatments Options for Uterine Fibroids (COMPARE-UF) Study is a multisite national registry of eight clinic centers across the United States. PATIENT(S): Reproductive-aged women undergoing surgery for symptomatic uterine fibroids. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): We used life-table methods to estimate cumulative probabilities and 95% confidence intervals (CI) of pregnancy and live birth by the myomectomy route during 12, 24, and 36 months of follow-up (2015-2019). We also conducted 12-month interval-based analyses that used logistic regression to estimate odds ratios and 95% CIs for associations of interest. In all analyses, we used propensity score weighting to adjust for differences across surgical routes. RESULT(S): Among 1,095 women who underwent myomectomy (abdominal = 388, hysteroscopic = 273, and laparoscopic = 434), 202 reported pregnancy and 91 reported live birth during 36 months of follow-up. There was little difference in the 12-month probability of pregnancy or live birth by route of myomectomy overall or among women intending pregnancy. In interval-based analyses, adjusted ORs for pregnancy were 1.28 (95% CI, 0.76-2.14) for hysteroscopic myomectomy and 1.19 (95% CI, 0.76-1.85) for laparoscopic myomectomy compared with abdominal myomectomy. Among women intending pregnancy, adjusted ORs were 1.27 (95% CI, 0.72-2.23) for hysteroscopic myomectomy and 1.26 (95% CI, 0.77-2.04) for laparoscopic myomectomy compared with abdominal myomectomy. Associations were slightly stronger but less precise for live birth. CONCLUSION(S): The probability of conception or live birth did not differ appreciably by the myomectomy route among women observed for 36 months postoperatively. CLINICAL TRIALS REGISTRATION NUMBER: (NCT02260752, clinicaltrials.gov).

Anxiety, Depression, and Quality of Life After Procedural Intervention for Uterine Fibroids.

Background: Quality of life (QOL) and psychological health has been reported to be decreased among women with gynecological conditions such as uterine fibroids (UFs). Materials and Methods: Women enrolled in the Comparing Options for Management: PAtient-centered REsults for Uterine Fibroids (COMPARE-UF) registry, receiving procedural therapy for symptomatic UFs, were eligible for this analysis if they completed a series of health-related QOL surveys administered at three time points (baseline, 6-12 weeks postprocedure, and 1 year postprocedure; n = 1486). Ethical approval for this study was obtained at each recruiting site and the coordinating center (NCT02260752, clinicaltrials.gov). Results: More than 26% (n = 393) of women reported moderate anxiety/depression on the baseline anxiety/depression domain of the Euro-QOL 5-dimension instrument. At both the 6-12 weeks and 1-year postprocedural follow-up, there was significant improvement in the UF QOL symptom severity score (p < 0.001, p < 0.001), the total UF symptom QOL score (p < 0.001, p < 0.001), and the Euro-QOL 5-dimension visual analog scale (p < 0.001, p = 0.004) compared with the preprocedural baseline scores. The reporting of anxiety/depression decreased by 66.4% among women who were at baseline, whereas 5.6% of women previously reporting no anxiety/depression reported anxiety/depression at the 1-year follow-up. Conclusion: UF symptoms were more severe among women reporting anxiety/depression at baseline. At the 1-year follow-up, health-related QOL scores improved among all women and the prevalence of anxiety/depression decreased in most, but not all women, whereas severity of anxiety/depression worsened in a small percentage of women (5.6%). Overall, these results suggest that UF treatment improves symptoms of anxiety/depression associated with symptomatic UFs.