Exposure to Perfluoroalkyl Substances and Associations with Pubertal Onset and Serum Reproductive Hormones in a Longitudinal Study of Young Girls in Greater Cincinnati and the San Francisco Bay Area.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS), endocrine disrupting chemicals with worldwide exposure, cause changes in mammary gland development in rodents. A few human studies report delay in pubertal events with increasing perfluorooctanoic acid (PFOA) exposure, but to our knowledge none have examined reproductive hormone levels at thelarche. METHODS: In a cohort of Greater Cincinnati (GC) and San Francisco Bay Area (SFBA) girls recruited at 6-8 years of age, clinical examinations were conducted annually or semiannually with sequential Tanner staging. PFAS concentrations were measured in the first serum sample of 704 girls. In 304 GC girls, estradiol (E2), estrone (E1), testosterone (T), and dihydroepiandrosterone sulfate (DHEAS) were measured in serum at four time points around puberty. Relationships between PFAS and age at thelarche, pubarche, and menarche were analyzed using survival and structural equation models. The association between PFAS and reproductive hormones was assessed using linear regression models. RESULTS: Median PFOA serum concentrations in GC (N=353, 7.3 ng/mL) and the SFBA (N=351, 5.8 ng/mL) were higher than in the U.S. POPULATION: In multivariable Cox proportional hazard models [adjusted for race, body mass index (BMI)], increasing serum log-transformed PFOA was associated with a delay in pubarche [hazard ratio (HR)=0.83; 95% CI: 0.70, 0.99] and menarche (HR=0.04; 95% CI: 0.01, 0.25). Structural equation models indicated a triangular relationship between PFOA, BMI percentile, and the age at the pubertal milestone. Increased PFOA had a statistically significant direct effect of delay on all three milestones, as did BMI. Perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (Me-PFOSA-AcOH) also were associated with later thelarche, and Me-PFOSA-AcOH also with later pubarche. PFOA was inversely associated with DHEAS (p<0.01), E1 (p=0.04), and T (p=0.03) concentrations at 6 months prior to puberty. CONCLUSIONS: PFAS may delay pubertal onset through the intervening effects on BMI and reproductive hormones. The decreases in DHEAS and E1 associated with PFOA represent biological biomarkers of effect consistent with the delay in onset of puberty. https://doi.org/10.1289/EHP11811.

Migraine and its association with pubertal maturation and behavioral traits among adolescent girls.

OBJECTIVE: To determine if the ages at pubertal milestones are associated with the prevalence of adolescent migraine. BACKGROUND: Migraine headaches are a common disease in adolescent girls. Past studies have evaluated the relationship between age of onset of menarche and migraine headache, but none have studied earlier pubertal milestones such as thelarche and pubarche. METHODS: In this cross-sectional study, a previously validated questionnaire was administered to girls (15-18 years) in Breast Cancer and the Environment Research Program puberty cohort to ascertain if they met criteria for migraine over the past year. Ages of pubertal development were ascertained by serial examinations beginning at 6-8 years of age and ending in late puberty. Logistic regression analyses determined if age of onset of each pubertal milestone (thelarche, pubarche, menarche separately) was associated with adolescent migraine after adjusting for other risk factors. RESULTS: Of 761girls, 222 (29.2%) met the criteria for migraine. Later thelarche was associated with a lower odds of adolescent migraine (OR 0.83; 95% CI 0.72-0.97, p = 0.019). In models further adjusted for BASC-2 internalizing problems (n = 490), both later thelarche (OR 0.78; 95% CI 0.64-0.96, p = 0.016) and later menarche (OR 0.81; 95%CI 0.67-0.98, p = 0.026) were associated with a lower migraine prevalence. Internalizing problems (OR 1.05; 95% CI 1.03-1.07) externalizing problems (OR 1.05; 95% CI 1.02-1.07) and behavioral symptoms (OR 1.05; 95% CI 1.03-1.08) were associated with increased prevalence of migraine in separate models. CONCLUSIONS: Age of onset of thelarche and menarche, and internalizing, externalizing, and behavioral symptoms were all associated with adolescent migraine.

Adverse Effects of Early Puberty Timing in Girls and Potential Solutions.

Given the global secular declining trends of the age at puberty and its relevant mechanisms, as illustrated in the first part of this series, the present part will discuss the public health implications of early puberty and potential clinical and public health measures. Although the major effect of earlier maturation impacts adolescents' mental health and likelihood of engaging in risky behaviors, there are also effects in adulthood on cardiometabolic health, especially type 2 diabetes, and an increased risk of certain cancers, especially hormone-related cancers such as breast cancer. The paper ends with recommendations for clinical management, especially for girls who should receive further evaluation, as well as recommendations for the patient and her family and public health considerations.

Trends Toward Earlier Puberty Timing in Girls and Its Likely Mechanisms.

This is the first of two installments examining early puberty in girls. The first paper will discuss secular trends in onset of puberty and the possible mechanisms to explain these developments. The potential etiologies examined will include the role of endocrine-disrupting chemicals and obesogens, the impact of body mass index and obesity, genetic and biologic pathways, and the influence of lifestyle behaviors. The second paper of the two-part series will examine the potential health impacts of early puberty on young and adult women and offer suggestions for clinical management and public health prevention.

The Association between Sex Hormones, Pubertal Milestones and Benzophenone-3 Exposure, Measured by Urinary Biomarker or Questionnaire.

Experimental studies have suggested benzophenone-3 (BP-3), a sunscreen ingredient, may have endocrine-disrupting properties. A cohort of girls were recruited at ages 6-7 years and returned semi-annually for pubertal maturation staging, provided blood for serum hormone analyses [estradiol, estrone, testosterone, dehydroepiandrosterone-sulfate (DHEA-S)], and urine to measure BP-3 concentrations. We found a significant negative linear association between amount of reported sunscreen use and testosterone levels at the onset of puberty (N = 157, adjusted ß = -0.0163, 97.5% CI:-0.0300,-0.0026). The 2nd quartile of the BP-3 biomarker had earlier thelarche compared to the 1st quartile (N = 282, adjusted HR = 1.584, 97.5% CI:1.038,2.415). Results suggest that higher report of sunscreen use may be associated with lower testosterone levels at thelarche and a non-linear relationship between the BP-3 urinary biomarker and onset of puberty, although the clinical significance of the finding is limited and may be a random effect. Improved methods of BP-3 exposure characterization are needed.

The Impact of Macronutrient Intake on Sex Steroids During Onset of Puberty.

INTRODUCTION: Increased fiber intake has been associated with decreased breast cancer risk, while increased animal protein intake with increased risk. The objective of this study is to examine the relationship of dietary fiber and protein intake to estrogen and sex hormone-binding globulin (SHBG) concentrations at puberty onset. METHODS: These analyses were conducted using the Cincinnati puberty cohort of the Breast Cancer and the Environment Research Program, with girls followed every 6 months from ages 6 and 7. The analyses included serum measurements at 6-month intervals for estrogen and SHBG concentrations, from 18 months prior to breast stage 2 (onset of puberty). Dietary intake was documented via 24-hour dietary recalls every 3 months. Dietary factors of interest included total energy intake; total and animal protein; total, soluble, and insoluble fiber; and lignan and flavanol intake. RESULTS: This study included 260 participants who generated 871 serum specimens and 3,000 days of diet intake. In longitudinal models, estradiol was associated inversely with insoluble fiber intake; estrone positively with animal protein intake; SHBG with greater insoluble fiber and lower total protein intake; and ratio of estrone to SHBG, a measure of bioavailable estrogen, positively with animal protein. CONCLUSIONS: Greater protein intake, especially animal protein, led to greater estrogen concentrations and lower SHBG; greater animal protein and greater caloric intake led to increased bioavailable estrogen. This relationship may have served an evolutionary advantage in the past for greater fertility with adequate high-quality protein; in contemporary women, a modest decrease in animal protein may be beneficial in reducing breast cancer risk.

Childhood Socioeconomic Status and Menarche: A Prospective Study.

PURPOSE: The relationship between socioeconomic status (SES) and menarche has implications for understanding social level influences on early life development and adult disease, including breast cancer, but remains ill defined. We report here results from the Breast Cancer and the Environment Research Program, which permitted a longitudinal study of age at menarche in relationship to childhood SES in a diverse cohort of 1,069 girls across three urban areas of the United States. METHODS: We assessed the association of SES index quintiles with age at pubertal onset with breast budding and subsequent tempo to the age at menarche between 2004 and 2015 using multiple-event Cox regression models to estimate hazard ratios and 95% confidence intervals. RESULTS: In an unadjusted model, lower SES was predictive of both earlier pubertal onset and tempo and thus earlier age at menarche in trends across quintiles. After adjusting for the potentially mediating effects of body mass index, SES trends remained significant for both outcomes. After adjusting for both body mass index and race/ethnicity, the association with SES remained substantial for pubertal onset but was much diminished and nonsignificant for tempo and thus age at menarche. CONCLUSIONS: These results suggest that a lower SES environment and social adversity affect the age at menarche primarily by hastening pubertal onset rather than by shortening tempo.

Girls' Pubertal Timing and Tempo and Mental Health: A Longitudinal Examination in an Ethnically Diverse Sample.

PURPOSE: Earlier timing and faster tempo of puberty have been linked to adolescents' poor mental health. Previous research rarely adjusted for childhood mental health, did not use physical examination to assess puberty, and excluded Latinas and Asian Americans. This study addressed these limitations. METHODS: We followed 822 girls, recruited at ages 6-8, for 8 years. Breast and pubic hair development and anxiety and depressive symptoms were assessed prospectively and repeatedly. Structural equation models tested whether pubertal timing and tempo were associated with adolescent mental health symptoms and whether associations varied by ethnicity. Models were adjusted for childhood mental health symptoms, body mass index, and family income. RESULTS: Earlier breast development was associated with higher depressive symptoms among whites (ß = -.19; p < .01) and higher anxiety symptoms among Latinas (ß = -.26; p < .05), but lower depressive symptoms among Asians (ß = .24, p < .05). Later pubic hair development (b = .24; p < .05) and faster pubic hair tempo (ß = .26; p < .01) were associated with higher anxiety symptoms among Latinas. Faster pubic hair tempo was associated with lower depressive symptoms among Asians (ß = -.34; p < .05). Tempo of breast development showed no associations. CONCLUSIONS: Findings confirmed that earlier breast development was associated with higher mental health symptoms for Latina and white girls but was protective among Asians. Results for pubic hair and pubertal tempo were inconsistent, requiring future examination. While targeted interventions to prevent mental health problems among early-maturing girls are critical, there is variability among who might benefit most.

Pubertal Growth, IGF-1, and Windows of Susceptibility: Puberty and Future Breast Cancer Risk.

PURPOSE: Risk markers for breast cancer include earlier onset of menarche (age at menarche [AAM]) and peak height velocity (PHV). Insulin-like growth factor-1 (IGF-1) is associated with pubertal milestones, as well as cancer risk. This study examined the relationships between pubertal milestones associated with breast cancer risk and hormone changes in puberty. METHODS: This is a longitudinal study of pubertal maturation in 183 girls, recruited at ages 6-7, followed up between 2004 and 2018. Measures included age at onset of puberty, and adult height attained; PHV; AAM; adult height, and serum IGF-1, and estrone-to-androstenedione (E:A) ratio. RESULTS: PHV was greatest in early, and least in late maturing girls; length of the pubertal growth spurt was longest in early, and shortest in late maturing girls. Earlier AAM was related to greater PHV. IGF-1 concentrations tracked significantly during puberty; higher IGF-1 was related to earlier age of PHV, earlier AAM, greater PHV, and taller adult height. Greater E:A ratio was associated with earlier AAM. CONCLUSIONS: Factors driving the association of earlier menarche and pubertal growth with breast cancer risk may be explained through a unifying concept relating higher IGF-1 concentrations, greater lifelong estrogen exposure, and longer pubertal growth period, with an expanded pubertal window of susceptibility.

Onset of Puberty: Mother Knows Best.

STUDY OBJECTIVE: Several strategies have been proposed to determine onset of puberty without examination by a trained professional. This study sought to evaluate a novel approach to determine onset of puberty in girls. DESIGN, SETTING, AND PARTICIPANTS: This study used the Cincinnati cohort of the Breast Cancer and the Environment Research Program. Girls were recruited at 6-7 years of age and followed every 6 months in the initial 6 years, and annually thereafter. Breast maturation and foot length were performed at each visit by health professionals certified in those methods. Mothers were asked to provide the age at which they believed that their daughter's shoe size had increased more rapidly. RESULTS: These analyses include 252 participants. Age at increase in shoe size was correlated to age at onset of puberty (r = 0.21) and increase in foot length (r = 0.24). The difference of reported age of increased shoe size was 0.46 years before breast development. CONCLUSION: Reported increase in shoe size occurred somewhat earlier and was significantly correlated to age of breast development. These preliminary results suggest that mother's report of increase in shoe size appear to be as accurate as reports of other indirect methods of determining onset of puberty, such as self- or maternal estimates of breast development.

Pubertal Development: What's Normal/What's Not.

Onset of puberty, as defined by breast stage 2, appears to be starting at younger ages since the 1940s. There is an ongoing controversy regarding what is normative, as well as what is normal, and the evaluation that is deemed necessary for girls maturing before 8 years of age. There are potential implications of earlier pubertal timing, including psychosocial consequences during adolescence, as well as longer term risks, such as breast cancer and cardiometabolic risks. There are additional consequences derived from slower pubertal tempo, for age of menarche has not decreased as much as age of breast development; these include longer interval between sexual initiation and intentional childbearing, as well as a broadened window of susceptibility to endocrine-related cancers.

Worldwide Secular Trends in Age at Pubertal Onset Assessed by Breast Development Among Girls: A Systematic Review and Meta-analysis.

Importance: The initial clinical sign of pubertal onset in girls is breast gland development (thelarche). Although numerous studies have used recalled age at menarche (first menstruation) to assess secular trends of pubertal timing, no systematic review has been conducted of secular trends of thelarche. Objectives: To systematically evaluate published data on pubertal timing based on age at thelarche and evaluate the change in pubertal onset in healthy girls around the world. Data Sources: A systematic literature search was performed in PubMed and Embase of all original peer-reviewed articles published in English before June 20, 2019. Study Selection: Included studies used clinical assessment of breast development in healthy girls and used adequate statistical methods, including the reporting of SEs or CIs. The quality of the articles was evaluated by assessing study design, potential sources of bias, main characteristics of the study population, and methods of statistical analysis. Data Extraction and Synthesis: In accordance with PRISMA guidelines, all articles were assessed for eligibility independently by 2 authors. Weighted regression analysis was performed using a random-effects model. Main Outcomes and Measures: Studies examining age at thelarche (development of Tanner breast stage 2) in healthy girls. Results: The literature search resulted in a total of 3602 studies, of which 30 studies fulfilled the eligibility criteria. There was a secular trend in ages at thelarche according to race/ethnicity and geography. Overall, the age at thelarche decreased 0.24 years (95% CI, -0.44 to -0.04) (almost 3 months) per decade from 1977 to 2013 (P = .02). Conclusions and Relevance: The age at thelarche has decreased a mean of almost 3 months per decade from 1977 to 2013. A younger age at pubertal onset may change current diagnostic decision-making. The medical community needs current and relevant data to redefine "precocious puberty," because the traditional definition may be outdated, at least in some regions of the world.

Longitudinal study of age of menarche in association with childhood concentrations of persistent organic pollutants.

BACKGROUND: Age at female puberty is associated with adult morbidities, including breast cancer and diabetes. Hormonally active chemicals are suspected of altering pubertal timing. We examined whether persistent organic pollutants (POPs) are associated with age at menarche in a longitudinal study. METHODS: We analyzed data for females enrolled at age 6-8 years in the Breast Cancer and Environment Research Program from California and Ohio. Participants were followed annually 2004-2013 and provided serum (mean age 7.8 years) for measurement of polychlorinated biphenyl (PCB), organochlorine pesticide (OCP), and polybrominated diphenyl ether (PBDE) concentrations. Age of menarche was assigned based on parental and participant reported dates and ages of menarche. Adjusted hazard ratios (aHRs) for menarchal onset were calculated with Cox proportional regression. Body mass index (BMI), potentially on the causal pathway, was added to parallel analyses. RESULTS: Age of menarche was later with higher summed PCB levels (median 11.9 years in quartile 1 [Q1] versus 12.7 in quartile 4 [Q4]) and OCP levels (12.1 years versus 12.4, respectively). When adjusting for all covariates except BMI, higher POP concentrations were associated with later age at menarche (Q4 versus Q1 aHRs: PBDEs 0.75 [95% CI 0.58, 0.97], PCBs 0.67 [95% CI 0.5, 0.89], and OCPs 0.66 [95% CI 0.50, 0.89]). Additional adjustment for BMI attenuated aHRs; PCB aHR approached the null. CONCLUSION: Findings revealed later onset of menarche with higher concentrations of certain POPs, possibly through an association with BMI. Altered pubertal timing may have long lasting effects on reproductive health and disease risk, so continued attention is important for understanding the biological processes affected by hormonally active chemicals.

Sex Hormone Phenotypes in Young Girls and the Age at Pubertal Milestones.

CONTEXT: The age of pubertal onset is influenced by many variables in young girls. Previous studies have not examined sex hormones longitudinally around the time of breast development and their relationship to pubertal onset. OBJECTIVE: We sought to use an unbiased statistical approach to identify phenotypes of sex hormones in young girls and examine their relationship with pubertal milestones. DESIGN AND SETTING: Longitudinal observational study. PARTICIPANTS AND MAIN OUTCOME MEASURES: In 269 girls, serum concentrations of steroid sex hormones [estradiol (E2), estrone, testosterone, and dehydroepiandrosterone sulfate] were measured by HPLC-mass spectrometry at time points before, at, and after thelarche. Girls were classified into four hormone phenotypes using objective principal components and cluster analyses of longitudinal hormone data. The association between the identified phenotypes and age of pubertal milestones was estimated using Cox proportional hazards modeling. RESULTS: Mean ages at thelarche, pubarche, and menarche were 9.02, 9.85, and 12.30 years, respectively. Girls with low levels of all four hormones, phenotype 3b, were youngest at thelarche (8.67 years); those in phenotype 2, with the highest E2 levels and E2 surge 6 months after thelarche, were youngest at menarche (11.87 years) with shortest pubertal tempo. When controlling for race, maternal age of menarche, caregiver education, and body mass, different phenotypes were associated with the age of pubertal events. CONCLUSIONS: Hormone phenotypic clustering can identify clinically relevant subgroups with differing ages of thelarche, pubarche, and menarche. These findings may enhance the understanding of timing of pubertal milestones and risk of adult disease.

Complex relationships between perfluorooctanoate, body mass index, insulin resistance and serum lipids in young girls.

BACKGROUND: Perfluorooctanoate (PFOA) has been used extensively in the manufacture of both commercial and household products. PFOA serum concentrations have been associated with adverse health effects, including lower body mass in children and infants. OBJECTIVE: To determine if there is an association between serum PFOA concentration and body mass, serum insulin and lipid profile in exposed young girls. METHODS: We conducted a cross-sectional study of PFAS environmental biomarkers and insulin resistance in 6 to 8 year-old girls from Greater Cincinnati (n=353). In 2004-2006, blood samples were obtained to measure polyfluoroalkyl substances (PFAS), fasting insulin, glucose and lipids. Clinical exams included anthropometric measurements and pubertal maturation staging. Linear regression and mediation analyses, specifically structural equation modeling (SEM), were used to determine the strength and direction of the relationships between PFAS, pubertal maturation status, body mass index (BMI), cholesterol and insulin resistance. RESULTS: The median PFOA (7.7ng/ml) was twice the National Health and Nutrition Examination Survey (2005-2006). Only PFOA, a PFAS sub-species, showed statistically significant relationships with the outcomes. In regression models, PFOA was associated with decreased BMI and waist-to-height ratio (p=0.0008; p=0.0343), HDL-cholesterol (p=0.0046) and had a borderline inverse association with the HOMA Index of insulin resistance (p=0.0864). In SEM, PFOA retained an inverse relationship with BMI (p<0.0001) but the relationships with HOMA and HDL-cholesterol were no longer statistically significant. Pubertal initiation (Tanner breast or pubic stage 2 or greater) and BMI were associated with increased HOMA Index (p<0.0001). CONCLUSIONS: These findings suggest PFOA exposure in young girls affects both BMI and ultimately insulin resistance. In mediation analysis with puberty in the model, the direct effects of PFOA on insulin resistance and were reduced.

Impact of Pubertal Maturation and Chronologic Age on Sex Steroids in Peripubertal Girls.

CONTEXT: There is a 4- to 5-year variation in age of breast maturation in girls. OBJECTIVE: To examine longitudinal changes in sex hormone values relative to chronologic age and time relative to breast maturation. SETTING AND DESIGN: Longitudinal observational study into which girls were recruited at 6 to 7 years of age and followed up every 6 months. MAIN OUTCOME MEASURES: Maturation status, chronologic age, race, and fasting blood specimen data were obtained. Hormones were analyzed at 6-month intervals between 2 years before and 1 year after breast maturation, using HPLC tandem mass spectroscopy. RESULTS: Estradiol and estrone levels correlated with chronologic age (R = 0.350 and 0.444, respectively); time was correlated relative to breast maturation (R = 0.222 and 0.323, respectively; all correlations, P < 0.0001). In generalized estimating equation (GEE) models, chronologic age and time relative to pubertal onset were significantly associated with serum estradiol, with similar results for estrone. Local estimated scatterplot smoothing for estradiol and estrone, by chronologic age, demonstrated differences between black and white girls, especially between 8.5 and 11 years of age, but not by race in time relative to breast maturation. Testosterone level was correlated to chronologic age (R = 0.362) and time relative to breast maturation (R = 0.259); in the GEE model, only chronologic age was significant. CONCLUSION: Chronologic age as well as time relative to onset of puberty provided unique information regarding estradiol and estrone concentrations in peripubertal girls. Serum estrogen concentrations should be evaluated with reference to chronologic age and race.

"Complementary Medicine": Complementary and Alternative Health Approaches in Pediatric and Adolescent Gynecology.

Complementary and alternative health care approaches are prevalent in the patients and families served by practitioners in pediatric and adolescent gynecology. This article addresses gaps in knowledge, including new terminology, prevalence of use, rates of and reasons behind nondisclosure, and potential interactions of herbal products with prescribed medication. It closes with practical complementary health approaches to the adolescent with dysmenorrhea.

Lead exposure during childhood and subsequent anthropometry through adolescence in girls.

INTRODUCTION: Cross-sectional studies suggest that postnatal blood lead (PbB) concentrations are negatively associated with child growth. Few studies prospectively examined this association in populations with lower PbB concentrations. We investigated longitudinal associations of childhood PbB concentrations and subsequent anthropometric measurements in a multi-ethnic cohort of girls. METHODS: Data were from The Breast Cancer and the Environment Research Program at three sites in the United States (U.S.): New York City, Cincinnati, and San Francisco Bay Area. Girls were enrolled at ages 6-8 years in 2004-2007. Girls with PbB concentrations collected at ≤10 years old (mean 7.8 years, standard deviation (SD) 0.82) and anthropometry collected at ≥3 follow-up visits were included (n = 683). The median PbB concentration was 0.99 µg/d (10th percentile = 0.59 µg/dL and 90th percentile = 2.00 µg/dL) and the geometric mean was 1.03 µg/dL (95% Confidence Interval (CI): 0.99, 1.06). For analyses, PbB concentrations were dichotomized as <1 µg/dL (n = 342) and ≥1 µg/dL (n = 341). Anthropometric measurements of height, body mass index (BMI), waist circumference (WC), and percent body fat (%BF) were collected at enrollment and follow-up visits through 2015. Linear mixed effects regression estimated how PbB concentrations related to changes in girls' measurements from ages 7-14 years. RESULTS: At 7 years, mean difference in height was -2.0 cm (95% CI: -3.0, -1.0) for girls with ≥1 µg/dL versus <1 µg/dL PbB concentrations; differences persisted, but were attenuated, with age to -1.5 cm (95% CI: -2.5, -0.4) at 14 years. Mean differences for BMI, WC, and BF% at 7 years between girls with ≥1 µg/dL versus <1 µg/dL PbB concentrations were -0.7 kg/m2 (95% CI: -1.2, -0.2), -2.2 cm (95% CI: -3.8, -0.6), and -1.8% (95% CI: -3.2, -0.4), respectively. Overall, these differences generally persisted with advancing age and at 14 years, differences were -0.8 kg/m2 (95% CI: -1.5, -0.02), -2.9 cm (95% CI: -4.8, -0.9), and -1.7% (95% CI: -3.1, -0.4) for BMI, WC, and BF%, respectively. CONCLUSIONS: These findings suggest that higher concentrations of PbB during childhood, even though relatively low by screening standards, may be inversely associated with anthropometric measurements in girls.

Comprehension and perceptions of study participants upon receiving perfluoroalkyl substance exposure biomarker results.

BACKGROUND: Measurement of environmental biomarkers in biomedia is increasingly used as a method of exposure characterization in human population studies. Reporting the results of biomarker measurements back to study participants has been controversial, including questions of ethics and whether the study participants would want to receive and would understand the results. METHODS: Recently we mailed individual measurements of two serum biomarkers, perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) to participants in three exposure studies of persons living in the Ohio River Valley, of whom 60 were parents of children who had been sampled. Many had serum concentrations of PFOA above the US population 95th percentile value. Reporting forms used in the three studies were somewhat different (either tables or charts for comparison to US population values) and varied in complexity. With all reports, we included information about concentrations of PFOA and PFOS in the general population, and a survey designed to ascertain the opinions of the study participants about the information they received. RESULTS: Approximately 33% (273/821) returned the survey, and of those, 96% reported that they were pleased that we had sent them the report. Most (86%) responded that the results were easy to understand and the enclosed fact sheet was helpful in answering questions (87%). Regarding the amount of information, most felt that we provided the "right amount" (78%) but some "too much" (7%) and some "too little" (15%). The majority (53%) were surprised at their serum concentrations. Of those with serum values > 13.0 ng/mL, 74% responded that they thought their serum concentration was "high", but only 22% of those with serum concentrations ≤5.6 responded that their concentration was "low". Surprisingly, many talked to no one about their levels; those who did were most likely to discuss the report with family members. CONCLUSIONS: Reporting back individual environmental biomarker results is generally well received by study participants, and those with high concentrations perceived them to be high. Questions remain as to why study participants did not discuss their results with others.

Age of Menarche in a Longitudinal US Cohort.

STUDY OBJECTIVE: Menarche is a critical milestone in a woman's life, and historically has been determined using several approaches. The goals of this study were to: (1) determine age at menarche from multiple reports of parents and adolescent participants in a prospective study; (2) examine factors affecting age at menarche; and (3) determine correlates of menarche and pubertal tempo. DESIGN: Longitudinal observational study. SETTING: Three sites of the Breast Cancer and the Environment Research Program. PARTICIPANTS: Girls enrolled at 6-8 years of age. INTERVENTIONS AND MAIN OUTCOME MEASURES: Parental and participant reported age of menarche, and tempo of puberty. RESULTS: There were 946 girls who were assigned an age of menarche. The correlation between parent and participant reports was high (Spearman R = 0.799, P < .001), and the difference was insignificant. Median age at menarche overall was 12.25 years. Compared with black participants, Hispanic girls were more likely to have menarche earlier, whereas white and Asian girls were more likely to have menarche later. Age of menarche was highly correlated with age of breast development (Spearman R = 0.547; P < .001), and inversely with body mass index (Spearman R = -0.403; P < .001). Tempo (interval of age of breast development to menarche) was slower in those with earlier breast development. CONCLUSION: Parental and adolescent reports of menarche are highly correlated. Earlier breast maturation was associated with slower tempo through puberty. Body mass index had a greater effect on age at menarche than did race and ethnicity.