Subgroups of pelvic pain are differentially associated with endometriosis and inflammatory comorbidities: a latent class analysis.

ABSTRACT: Chronic pelvic pain is heterogeneous with potentially clinically informative subgroups. We aimed to identify subgroups of pelvic pain based on symptom patterns and investigate their associations with inflammatory and chronic pain-related comorbidities. Latent class analysis (LCA) identified subgroups of participants (n = 1255) from the Adolescence to Adulthood (A2A) cohort. Six participant characteristics were included in the LCA: severity, frequency, and impact on daily activities of both menstruation-associated (cyclic) and non-menstruation-associated (acyclic) pelvic pain. Three-step LCA quantified associations between LC subgroups, demographic and clinical variables, and 18 comorbidities (10 with prevalence ≥10%). Five subgroups were identified: none or minimal (23%), moderate cyclic only (28%), severe cyclic only (20%), moderate or severe acyclic plus moderate cyclic (9%), and severe acyclic plus severe cyclic (21%). Endometriosis prevalence within these 5 LCA-pelvic pain-defined subgroups ranged in size from 4% in "none or minimal pelvic pain" to 24%, 72%, 70%, and 94%, respectively, in the 4 pain subgroups, with statistically significant odds of membership only for the latter 3 subgroups. Migraines were associated with significant odds of membership in all 4 pelvic pain subgroups relative to those with no pelvic pain (adjusted odds ratios = 2.92-7.78), whereas back, joint, or leg pain each had significantly greater odds of membership in the latter 3 subgroups. Asthma or allergies had three times the odds of membership in the most severe pain group. Subgroups with elevated levels of cyclic or acyclic pain are associated with greater frequency of chronic overlapping pain conditions, suggesting an important role for central inflammatory and immunological mechanisms.

Urinary cadmium and endometriosis prevalence in a US nationally representative sample: results from NHANES 1999-2006.

STUDY QUESTION: Is exposure to toxic metal cadmium associated with increased endometriosis prevalence among a nationally representative sample of the US population? SUMMARY ANSWER: Concentrations of urinary cadmium, a long-term biomarker (10-30 years) of cadmium exposure, were associated with an increased prevalence of endometriosis. WHAT IS KNOWN ALREADY: Cadmium exhibits estrogenic properties and may increase the risk of endometriosis, a gynecologic condition associated with substantial morbidity, for which estrogen has a central pathogenic role. Previous epidemiological studies of cadmium and endometriosis have yielded mixed results, with null, positive, and inverse associations being reported. STUDY DESIGN, SIZE, DURATION: We conducted a cross-sectional study using data from four cycles of the National Health and Nutrition Examination Survey (NHANES) 1999-2006. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study population comprised participants aged 20-54 years who had an endometriosis diagnosis, available data on urinary cadmium, and a glomerular filtration rate ≥60 ml/min/1.73 m2 (unweighted n = 1647). Urinary cadmium was measured by inductively coupled plasma-mass spectrometry, and we used urinary creatinine concentrations and covariate-adjusted standardization to account for urinary dilution. Self-reported diagnosis of endometriosis was ascertained by interview. We examined the association between quartiles of urinary cadmium and endometriosis using log-binomial regression to estimate adjusted prevalence ratios (aPRs) and 95% CIs. MAIN RESULTS AND THE ROLE OF CHANCE: We observed twice the prevalence of endometriosis for participants with cadmium concentrations in the second quartile (versus the first quartile) (aPR 2.0, 95% CI: 1.1, 3.9) and the third quartile (versus the first quartile) (aPR 2.0, 95% CI: 1.1, 3.7). Our data also suggested a 60% increased prevalence of endometriosis with urinary cadmium concentrations in the fourth quartile (versus the first quartile) (aPR 1.6, 95% CI: 0.8, 3.2). In a sensitivity analysis, restricting the study population to premenopausal participants with an intact uterus and at least one ovary (unweighted n = 1298), stronger associations accompanied by wider CIs were observed. LIMITATIONS, REASONS FOR CAUTION: We were limited by the ascertainment of urinary cadmium and endometriosis diagnosis at a single time point, given the cross-sectional study design, and we relied on self-report of endometriosis diagnosis. However, urinary cadmium characterizes long-term exposure and findings from validation studies suggest that misclassification of self-reported endometriosis diagnosis may be minimal. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that cadmium is associated with an increased endometriosis prevalence. Given the substantial morbidity conferred by endometriosis and that the general population is ubiquitously exposed to cadmium, further research is warranted to confirm our findings. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Institute of Nursing Research (grant R00NR017191 to K.U.) of the National Institutes of Health. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

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.

Soy-Based Infant Formula Feeding and Uterine Fibroid Development in a Prospective Ultrasound Study of Black/African-American Women.

BACKGROUND: Uterine fibroids are highly prevalent, benign tumors. They are the leading indication for hysterectomy, and Black women are disproportionally burdened. Soy-based infant formula contains phytoestrogens, and exposure during sensitive developmental windows may adversely affect the developing uterus; early phytoestrogen treatment in rodent studies led to detrimental uterine effects, including increased fibroid risk in Eker rats. Limited epidemiological studies also have suggested increased fibroid development with soy formula infant feeding. OBJECTIVE: The goal of this study was to examine the association between soy formula feeding in infancy and fibroid development in adulthood. METHODS: We evaluated this association among 1,610 Black/African-American women age 23-35 y in the Study of Environment, Lifestyle & Fibroids (SELF). Soy formula feeding data was gathered directly from the participants' mothers (89%). A standardized ultrasound examination was conducted during 4 clinic visits over 5 y to detect fibroids ≥0.5cm in diameter. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between soy formula feeding and incident fibroids adjusted for early-life and adult factors. Fibroid growth was calculated as change in log-volume for fibroids matched at successive visits. RESULTS: Of 1,121 fibroid-free participants at baseline, 150 (13%) were ever fed soy formula as infants, and 269 (24%) developed incident fibroids. We did not observe an association between ever being fed soy formula and incident fibroid risk (HR=1.08; 95% CI: 0.75, 1.54). However, participants fed soy formula within 2 months of birth and for >6 months (n=53) had an elevated risk of fibroid incidence in comparison with those never fed soy formula (HR=1.56; 95% CI: 0.92, 2.65). Fibroid growth rates did not differ. DISCUSSION: Adding support to limited human data, this prospective fibroid study found that soy-based formula feeding during infancy was associated with a suggestive increase in risk of ultrasound-identified incident fibroids in adulthood. https://doi.org/10.1289/EHP11089.

Cannabis smoking, tobacco cigarette smoking, and adenomyosis risk.

OBJECTIVE: To investigate cannabis smoking and tobacco cigarette smoking in relation to adenomyosis risk. DESIGN: We used data from a case-control study of adenomyosis conducted among enrollees ages 18-59 years of an integrated health care system in Washington State. The case-control study used 2 control groups given the challenge of selecting noncases when cases are diagnosed by hysterectomy. SUBJECTS: Cases (n = 386) were enrollees with incident, pathology-confirmed adenomyosis diagnosed between April 1, 2001, and March 31, 2006. The 2 control groups comprised hysterectomy controls (n = 233) with pathology-confirmed absence of adenomyosis and population controls (n = 323) with an intact uterus selected randomly from the health care system population and frequency matched to cases on age. EXPOSURE: Detailed data on cannabis and tobacco cigarette smoking history were ascertained through in-person structured interviews, allowing estimation of joint-years of cannabis smoking and pack-years of tobacco cigarette smoking. MAIN OUTCOME MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between cannabis smoking, tobacco cigarette smoking, and adenomyosis were estimated using multivariable unconditional logistic regression. Analyses were adjusted for age, reference year, menarche age, education, and pack-years of cigarette smoking (or joint-years of cannabis smoking). RESULTS: No association was observed between cannabis smoking history and adenomyosis risk. However, we did observe the suggestion of an association between ever tobacco cigarette smoking and adenomyosis risk, comparing cases to hysterectomy controls (OR, 1.3; 95% CI, 0.9-1.9) and population controls (OR, 1.2; 95% CI, 0.8-1.8). Our data suggested a 50% increased odds of adenomyosis with >15 pack-years of smoking (vs. never smoking), comparing cases to hysterectomy controls (OR, 1.5; 95% CI, 0.9-2.6; Ptrend=.135). The suggestion of a 40% increased adenomyosis odds was observed with smoking >5-15 pack-years (vs. never smoking), comparing cases to population controls (OR, 1.4; 95% CI, 0.8-2.4; Ptrend=0.136). CONCLUSION: In the first study of cannabis smoking and adenomyosis risk, no association was observed. However, our data suggested an increased odds of adenomyosis with history of tobacco cigarette smoking. Further research is warranted to replicate our results given the substantial morbidity with adenomyosis and frequency of cigarette smoking and recreational and medical cannabis use.

Breastfeeding history and adenomyosis risk using a novel case-control study design.

OBJECTIVE: To evaluate the association between breastfeeding history, including lifetime exclusive breastfeeding, and risk of adenomyosis. DESIGN: We used data from a case-control study designed with 2 control groups to address the challenge of selecting noncases for a valid epidemiologic study when cases are identified by hysterectomy. The case-control study was conducted among premenopausal and postmenopausal enrollees aged 18-59 years in a large, integrated health care system in western Washington state. PATIENT(S): Cases were enrollees with incident, pathology-confirmed adenomyosis diagnosed during 2001-2006 (n = 386). The 2 control groups were as follows: (1) randomly selected age-matched enrollees with intact uteri ("population controls," n = 323) and (2) hysterectomy controls (n = 233). INTERVENTION(S): Data on breastfeeding history were collected by in-person interviews. For each reported live birth, participants were asked whether they breastfed, along with infant age at supplemental feeding introduction and breastfeeding discontinuation. MAIN OUTCOME MEASURE(S): Among participants with at least 1 live birth (330 cases, 246 population controls, and 198 hysterectomy controls), we used unconditional logistic regression to estimate adjusted odds ratios and 95% confidence intervals (CIs) for the associations between the following: (1) ever breastfeeding, (2) ever breastfeeding for ≥8 weeks, (3) lifetime breastfeeding, and (4) lifetime exclusive breastfeeding and risk of adenomyosis. Analyses were adjusted for age, reference year, smoking, education, and parity. RESULT(S): In analyses comparing cases with population controls, we observed a 40% decreased odds of adenomyosis with a history of ever breastfeeding (adjusted odds ratio, 0.6; 95% CI, 0.3-1.0) and breastfeeding for ≥8 weeks (adjusted odds ratio, 0.6; 95% CI, 0.4-0.8). The strongest associations, 60%-70% decreased odds of adenomyosis, were observed with ≥12 months of lifetime breastfeeding (vs. <3 months) (adjusted odds ratio, 0.4; 95% CI, 0.2-0.6) and 9 to <12 months of lifetime exclusive breastfeeding (vs. <3 months) (adjusted odds ratio, 0.3; 95% CI, 0.2-0.6), comparing cases to population controls. In analyses using hysterectomy controls, we observed similar patterns of associations slightly attenuated in magnitude. CONCLUSION(S): Breastfeeding history was associated with a 40% decreased odds of adenomyosis, a condition that can confer substantial morbidity and requires hysterectomy for definitive treatment. The consistency of our findings with that of a previous study lends support that breastfeeding may modify risk of adenomyosis.

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).

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.

An Epidemiologic Review of Menstrual Blood Loss as an Excretion Route for Per- and Polyfluoroalkyl Substances.

PURPOSE OF REVIEW: Menstrual blood loss, a common physiologic occurrence, provides an excretion route for per- and polyfluoroalkyl substances (PFAS) since these chemicals are bound to proteins in blood. To increase awareness of this relationship in environmental epidemiology, we reviewed the available epidemiologic data on menstrual bleeding and PFAS concentrations. RECENT FINDINGS: Initial epidemiologic studies reported generally higher PFAS concentrations in men, menopausal women, and those with a history of hysterectomy compared to premenopausal women. Although subsequent studies investigating menstrual cycle characteristics observed somewhat discrepant results for menstrual irregularity and cycle length, consistent associations have been observed between heavy menstrual bleeding and lower PFAS concentrations. This review highlights the important role of menstrual bleeding on the excretion of PFAS. Given the high prevalence of menstrual bleeding in the population and the implications for environmental epidemiology, we provide recommendations to move this field forward.

Menstrual Products as a Source of Environmental Chemical Exposure: A Review from the Epidemiologic Perspective.

PURPOSE OF REVIEW: Menstrual bleeding is a regular, common occurrence in a substantial portion of the population. Menstruators may use more than 10,000 menstrual products over the lifetime. Given the potential for environmental chemicals in menstrual products to be absorbed by the vulvar and vaginal epithelium into systemic circulation, we reviewed the available data on menstrual products as a source of environmental chemical exposure. RECENT FINDINGS: Nearly two dozen studies have been conducted measuring environmental contaminants in menstrual products; all have detected environmental chemicals but had discrepant conclusions on exposure risks. Only three human studies have investigated menstrual product use and environmental chemical concentrations and all observed associations. Detection of environmental chemicals in menstrual products, in combination with challenges of exposure assessment, scarcity of human studies, and the exceedingly common occurrence of menstrual bleeding, motivates the need for further research. We provide recommendations to move this field forward.

Outdoor air pollution and anti-Müllerian hormone concentrations in the Sister Study.

BACKGROUND: Anti-Müllerian hormone (AMH) concentrations are a marker of ovarian reserve and are indicative of a woman's reproductive lifespan. Exposure to tobacco smoke has been associated with lower AMH concentrations; however, less is known about the association between ambient air pollution and ovarian reserve. METHODS: For 883 premenopausal Sister Study participants recruited between 2003 and 2009 in the United States, adult residential annual average concentrations of PM2.5, PM10, and NO2 were estimated using validated universal kriging models incorporating land-use regression. We estimated the distance in meters to the nearest major road for both adult enrollment and childhood residences. Serum AMH was measured using an ultrasensitive ELISA assay. Samples with AMH concentrations below the detection limit were analyzed using a picoAMH ELISA assay. Multivariable-adjusted linear regression was used to estimate the percent change in AMH in relation to ambient residential air pollution, categorized in quartiles and per interquartile range increase, and distance to a major roadway. RESULTS: Overall, we observed little to no evidence of associations between AMH and air pollution concentrations or proximity to roadways. Women in the highest quartile of NO2 exposure, a traffic-related pollutant, had higher estimated AMH concentrations (Q4 vs. Q1, 42.9%; 95% CI = -3.4, 111.4) compared with the lowest quartile. However, lower mean AMH concentrations were observed for women living closer to a major roadway (<50 m to nearest roadway vs. ≥200 m = -32.9%; 95% CI = -56.1, 2.6). CONCLUSIONS: We saw little consistent evidence to support an association between outdoor air pollution and diminished ovarian reserve in US women ages 35-54.

REPRODUCTIVE TOXICOLOGY: Pregnancy exposure to endocrine disrupting chemicals: implications for women's health.

Women are ubiquitously exposed to non-persistent endocrine disrupting chemicals (EDCs) from food contact materials and personal care products. Understanding the impacts of exposure to these chemicals on pregnancy and long-term health outcomes in women is a critical area of research that has been largely overlooked. This brief review focuses on the epidemiologic literature exploring associations of non-persistent EDCs - including phthalates, parabens, bisphenols, and triclosan - with maternal pregnancy outcomes and long-term health outcomes in women. We focus on the challenges of this research, particularly assessing non-persistent EDC exposures, aspects of study design, and statistical approaches. We conclude by reviewing the best practices for non-persistent EDC research with regards to pregnancy and women's health. Though limited, we found some evidence indicating that exposure to non-persistent EDCs is associated with pregnancy health. However, findings from these studies have been inconsistent and require corroboration. Recent studies have also proposed that non-persistent EDC exposures in pregnancy may adversely affect postnatal maternal health. To date, only a few studies have been conducted and have only focused on postpartum weight. More research is needed in this area to inform efforts to promote optimal health across the lifespan of women.

Early-life Farm Exposure and Ovarian Reserve in a US Cohort of Women.

BACKGROUND: In a previous exploratory study, we reported lower concentrations of the ovarian reserve biomarker anti-Müllerian hormone (AMH) in adulthood with prenatal farm exposure. We now examine this association as well as childhood farm exposure using enrollment data from the Sister Study, a large US cohort of women. METHODS: We collected prenatal and childhood farm exposure data by questionnaire and telephone interview. However, serum AMH data were available only for a nested subset: premenopausal women ages 35-54 subsequently diagnosed with breast cancer (n = 418 cases) and their matched controls (n = 866). To avoid potential bias from restricting analyses to only premenopausal controls, we leveraged the available cohort data. We used data from both premenopausal cases and controls as well as postmenopausal women ages 35-54 (n = 3,526) (all presumed to have undetectable AMH concentrations) and applied weights to produce a sample representative of the cohort ages 35-54 (n = 17,799). The high proportion of undetectable AMH concentrations (41%) was addressed using reverse-scale Cox regression. An adjusted hazard ratio (HR) <1.0 indicates that exposed individuals had lower AMH concentrations than unexposed individuals. RESULTS: Prenatal exposure to maternal residence or work on a farm was associated with lower AMH concentrations (HR 0.66; 95% confidence intervals [CI] = 0.48 to 0.90). Associations between childhood farm residence exposures and AMH were null or weak, except childhood contact with pesticide-treated livestock or buildings (HR 0.69; 95% CI = 0.40 to 1.2). CONCLUSIONS: Replication of the prenatal farm exposure and lower adult AMH association raises concern that aspects of prenatal farm exposure may result in reduced adult ovarian reserve.

Douching or Perineal Talc Use and Prevalent Fibroids in Young African American Women.

Background: Black women are at an increased risk of developing fibroids, but the cause is unclear. Douching and perineal talc use are common lifestyle exposures among Black women, and may be risk factors for fibroid development. Materials and Methods: This cross-sectional study consisted of Black women 23-35 years of age in the metropolitan Detroit area (n = 1693) without prior diagnoses of fibroids and intact uteri. Main exposures were ever douching (yes/no) and any perineal talc use (ever/never). Main outcomes were prevalent fibroids at baseline (yes/no) and total fibroid volume at baseline (no fibroids/

Cadmium Exposure and Ovarian Reserve in Women Aged 35-49 Years: The Impact on Results From the Creatinine Adjustment Approach Used to Correct for Urinary Dilution.

Cadmium is toxic to the ovaries in animal studies, but its association with diminished ovarian reserve in women is not established. We investigated urinary cadmium, a biomarker of long-term exposure, in relation to diminished ovarian reserve, as indicated by elevated serum follicle-stimulating hormone concentrations (≥10 IU/L), in women aged 35-49 years (unweighted n = 1,681). Using data from the Third National Health and Nutrition Examination Survey (1988-1994), we conducted Poisson regression to estimate adjusted relative risks and 95% confidence intervals. Because the best approach to correcting for urinary dilution in spot samples with creatinine remains controversial, we employed 3 approaches: standardization, covariate adjustment, and covariate-adjusted standardization. Our data suggested a modest association with standardization (highest quartile vs. lowest: relative risk (RR) = 1.3, 95% confidence interval (CI): 0.8, 1.9; P for trend = 0.06) and covariate-adjusted standardization (highest quartile vs. lowest: RR = 1.3, 95% CI: 0.9, 1.9; P for trend = 0.05) and a stronger association with covariate adjustment (highest quartile vs. lowest: RR = 1.8, 95% CI: 1.2, 2.9; P for trend = 0.01). The stronger association with covariate adjustment may reflect bias from conditioning on urinary creatinine, a collider in the hypothesized causal pathway. We conclude that cadmium may contribute to ovarian aging in women and that careful consideration of the creatinine adjustment approach is needed to minimize bias.

Depot Medroxyprogesterone Acetate Use and Blood Lead Levels in a Cohort of Young Women.

BACKGROUND: Injectable contraceptive use is common, with 74 million users worldwide. Use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) is associated with bone mineral density loss. We hypothesize that increased bone resorption with DMPA use allows for mobilization of the toxic metal lead stored in bone to blood, presenting users with increased systemic exposure to lead. OBJECTIVE: The objective of our study was to investigate the association between current DMPA use and blood lead concentrations. METHODS: We conducted a cross-sectional analysis using enrollment data from the Study of Environment, Lifestyle & Fibroids (SELF), a cohort of 1,693 African-American women who were 23-35 years of age. Data on DMPA use were collected by computer-assisted telephone interview. Blood lead concentrations were measured in whole blood samples among 1,548 participants (91% of cohort). We estimated the adjusted percent difference in blood lead concentrations and 95% confidence intervals (CI) between current DMPA users and nonusers using multivariable linear regression. RESULTS: Geometric mean blood lead concentration was 0.69µg/dL (95% CI: 0.67, 0.71). After adjustment, current DMPA users (7% of cohort) had blood lead concentrations that were 18% higher than those of nonusers (95% CI: 8%, 29%). Similar associations were observed with additional analyses to assess for potential bias from smoking, DMPA-induced amenorrhea, use of estrogen-containing contraceptives, having given birth in the prior year, and history of medical conditions or current medication use associated with bone loss. DISCUSSION: Our results indicate that current DMPA use is associated with increased blood lead concentrations. Further research, particularly in populations highly exposed to lead, is warranted to consider tradeoffs between the adverse effects of lead on human health and the importance of DMPA as a contraceptive option to prevent unintended pregnancy. https://doi.org/10.1289/EHP7017.

Epidemiology of Adenomyosis.

Adenomyosis, characterized by the presence of endometrial glands and stroma within the myometrium, can have a substantial impact on the quality of women's lives. Despite this, the epidemiologic research on this condition lags considerably behind that of other noncancerous reproductive health conditions. The lack of progress and knowledge is due in part to the challenges in designing valid epidemiologic studies, since the diagnosis of adenomyosis historically has been limited to the examination of uterine specimens from hysterectomy. This review describes the available data on the frequency of this condition and the epidemiologic investigation thus far into the risk factors for disease-highlighting the methodologic and inference challenges primarily around study sample selection. We conclude with providing recommendations for approaches to future epidemiologic study that capitalize on the advancements in imaging technology to detect adenomyosis and provide a fuller picture of the occurrence and risk factors for disease.

Environmental risk factors for endometriosis: A critical evaluation of studies and recommendations from the epidemiologic perspective.

PURPOSE OF REVIEW: Recent studies of environmental chemicals and endometriosis were critically evaluated from the epidemiologic perspective to identify aspects of study design and analyses that may contribute to discrepant results across studies. RECENT FINDINGS: Of the 29 studies reviewed, 12 studies used new approaches to population-based sampling. The remaining studies were conducted primarily among patients undergoing pelvic surgery; controls may not represent the exposure experience of the underlying study base, resulting in biased estimates of associations. Most studies used biologic specimens collected near diagnosis and varied in analytic approaches to minimize bias. Few studies investigated ovarian, deep-infiltrating, and peritoneal endometriosis presentations separately. SUMMARY: Recommendations to move the field forward include: (1) control selection from a defined study base, (2) exposure characterization during the etiologically-relevant window, (3) employment of best practices to minimize bias in analyses, and (4) separate consideration of endometriosis presentations that may be etiologically-distinct entities.

Comparison of Methodologies to Estimate Dietary Cadmium Intake in an Italian Population.

Cadmium is a metal that is toxic to humans, and the major source of cadmium exposure in the non-smoking general population is diet. To identify major food sources and lower exposure from diet, an accurate estimate of dietary cadmium intake is needed. Hence, the objectives of this study are to develop a method to assess dietary cadmium intake using a biomarker measurement and to improve the estimation of dietary cadmium intake when using a food frequency questionnaire (FFQ). In a random sample of an Italian population, we collected dietary habits by FFQ and measured cadmium in foods and beverages. These data were used to compute the estimated weekly dietary intake (WDI) of cadmium (µg) by kilogram (kg) of body weight (bw) (WDIFFQ). We also measured fasting serum cadmium levels by inductively-coupled plasma mass spectrometry. We used these data to develop a model for the estimation of the biomarker-derived dietary cadmium intake (WDIbio). In the 51 subjects recruited, the median level of serum cadmium was 0.041 µg/L (interquartile range (IQR): 0.030-0.054). The median WDIFFQ and WDIbio were 1.34 µg/kg bw/week (IQR: 0.86-1.70) and 0.72 µg/kg bw/week (IQR: 0.55-1.11), respectively. The correlation between the two estimates was low-to-moderate (r = 0.291). In exploratory analyses, the correlation was slightly higher in women and participants ages <50 years, and markedly higher in participants with body mass index <25 kg/m2 and smokers. Our approach allows for the dietary contribution to be isolated from the overall cadmium exposure measured with a biomarker; the estimated dietary cadmium intake was roughly similar to that estimated using the FFQ, especially in select subgroups. Future refinements to the biomarker-derived dietary cadmium intake approach should take into consideration additional sources of cadmium exposure, as well as factors affecting its absorption and metabolism.