Frank Biro

• MD
• Cincinnati Children's Hospital Medical Center

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 the...

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 the...

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, geneti...

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 the adolescent's menta...

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 analy...

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-...

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...

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...

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...

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 p...

Background 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. Methods This study utilized the Cincinnati cohort of the Breast Cancer and the Environment Research Program. Girls were recruited at 6-7...

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 publish...

Abtract 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 a...

Methods: We conducted a study of per- and polyfluoroalkyl substance biomarkers, including PFOA, in girls from Greater Cincinnati (CIN, N = 353) and the San Francisco Bay Area (SFBA, N = 351). PFOA was measured in the baseline serum sample collected in 2004-2007 of 704 girls at age 6-8 years. Mixed effects models were used to derive the effect of P...

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 a...

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 m...

Context There is a 4-5 year variation in age of breast maturation in girls. Objective Examine longitudinal changes in sex hormone values, relative to chronologic age and time relative to breast maturation. Setting and design Longitudinal observational study. Girls were recruited at 6 to 7 years of age and followed every six months. Main outcome...

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 prescrib...

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 measureme...

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 woul...

Study objectives: Menarche is a critical milestone in a woman's life, and historically has been determined through 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 impacting age at menarche; and 3) determine corr...

Purpose: This study aims to examine the longitudinal association between puberty and sleep in a diverse sample of girls and explore racial/ethnic differences in this association. Methods: Using latent growth curve modeling, the present study measured pubertal development (timing and rate) and sleep (wake time and bedtime) in 1,239 socioeconomica...

Screening for sexually transmitted infections (STIs) outside of traditional health-care facilities is limited by the privacy needed for sample collection. We explored the acceptability of privacy shelters for the self-collection of genital swabs and tested the use of privacy shelters during mobile STI screening. Attendees ≥14 years old at two outdo...

Background: Higher socioeconomic position (SEP) has been associated with increased risk of breast cancer. Its relationship with earlier age of pubertal onset, a risk factor for breast cancer, is less clear. Methods: We studied the relationship of SEP to pubertal onset in multiethnic cohort of 1237 girls aged 6-8 years at baseline. Girls in three...

Background: Industrial discharges of perfluorooctanoic acid (PFOA) to the Ohio River, contaminating water systems near Parkersburg, WV, were previously associated with nearby residents' serum PFOA concentrations above US general population medians. Ohio River PFOA concentrations downstream are elevated, suggesting Mid-Ohio River Valley residents a...

Background: Tobacco smoke contains known hormonally active chemicals and reproductive toxicants. Several studies have examined prenatal maternal smoking and offspring age at menarche, but few examined earlier pubertal markers, nor accounted for exposure during childhood. Our objective was to examine pre- and post-natal smoke exposure in relation t...

Phenolic compounds represent a class of environmental chemicals with potential endocrine disrupting capabilities. We investigated longitudinal associations of childhood exposures to phenols, from both man-made and natural sources, and subsequent measures of adiposity among girls enrolled in The Breast Cancer and Environment Research Program, 2004-2...

Background: Dietary phytoestrogens may alter hormonal activity in childhood. Flavonols and lignans are the most prevalent phytoestrogens in the Western diet.We examined whether higher intake of flavonols and lignans were associated with later age at menarche in a prospective study of young girls. Methods: 1044 girls ages 6-8 years (mean 7.3 yr)...

Objectives: Amphiregulin is a member of the epidermal growth factor family. In breast tissue, amphiregulin is a mediator of estrogen and progesterone signaling. The objectives were to examine the relationship of amphiregulin levels during peripuberty with estrogen levels. Methods: The participants in this analysis were a subset from a longitudin...

To study potential environmental influences on puberty in girls, we investigated urinary biomarkers in relation to age at menarche. Phenols and phthalates were measured at baseline (6–8 years of age). Menarche was ascertained over 11 years for 1051 girls with menarche and biomarkers. Hazards ratios were estimated from Cox models adjusted for race/e...

Background: There is an increasing adolescent population with severe obesity with impairments in social and romantic relationships that are seeking clinical weight management, including weight loss surgery (WLS). Objective: To document romantic, sexual and sexual risk behaviours in a clinical sample of adolescent females with severe obesity (BMI...

Background: Phthalates are environmental chemicals that may play a role in the development of obesity. Few studies have investigated longitudinal associations between postnatal phthalate exposures and subsequent anthropometric measurements in children. Methods: We collected data as part of The Breast Cancer and Environment Research Program at th...

Higher socioeconomic position (SEP) has been associated with increased risk of breast cancer. Its relationship with the age of menarche, which is inversely associated with risk of breast cancer, and to the age of pubertal onset, is less clear. We studied the relationship of SEP to pubertal onset in a multiethnic cohort of girls aged 6–8 years at ba...

Recent studies have documented earlier pubertal maturation in both girls and boys. Several factors have been proposed to account for earlier maturation. Epidemiologic studies have indicated that genetic factors are the most important influence contributing to the variability in the onset of puberty. Studies have also noted the association of elevat...

Purpose: Health research that includes youth and family stakeholders increases the contextual relevance of findings, which can benefit both the researchers and stakeholders involved. The goal of this study was to identify youth and family adolescent health priorities and to explore strategies to address these concerns. Methods: Stakeholders iden...

Environmental exposures to many phenols are documented worldwide and exposures can be quite high (>1μM of urine metabolites). Phenols have a range of hormonal activity, but knowledge of effects on child reproductive development is limited, coming mostly from cross-sectional studies. We undertook a prospective study of pubertal development among 123...

Perchlorate, thiocyanate and nitrate are sodium/iodide symporter (NIS) inhibitors that block iodide uptake into the thyroid, thus affecting thyroid function. Thyroid dysfunction can adversely affect somatic growth and development in children. To our knowledge, no studies have examined effects of NIS inhibitors on body size measures. We investigated...

Exposure to hormonally active chemicals could plausibly affect pubertal timing, so we are investigating this in the Breast Cancer and the Environment Research Program. Examine persistent organic pollutants (POPs) in relation to pubertal onset. Ethnically diverse cohorts of 6-8 year old girls (n=645) provided serum for measure of polybrominated diph...

To evaluate the effectiveness of a sexually transmitted infection (STI) intervention by a health educator that included partner notification, condom use, and retesting within 3 months. Retrospective chart review was conducted, and data were collected from 274 sexually active adolescent girls, aged 15 to 19 years, who were diagnosed with gonorrhea (...

Purpose Health research that includes youth and family stakeholders increases the contextual relevance of findings, which can benefit both the researchers and stakeholders involved. The goal of this study was to identify youth and family adolescent health priorities and to explore strategies to address these concerns. Methods Stakeholders identifi...

Background Early menarche is linked to higher incidence of adult asthma suggesting that earlier puberty may influence type 2 immune responses characteristic of allergic diseases. We examined the hypothesis that timing of breast and pubic hair development, which precede menarche, are associated with increased childhood atopic conditions.Methods Girl...

Background Exposures of children to phthalates, parabens, and bisphenol-A (BPA) are of concern because of their hormonal potential. These agents are found in a wide range of foods and packaging. We investigated whether intake of certain foods predict exposures to these chemicals in young girls. Methods Among 1101 girls (6–8 years at enrollment) fr...

Context: Studies of hormone changes in the peripubertal period note increases in adrenal hormones prior to increases in sex steroids. It is unclear how these processes are related to each other, except through this temporal relationship. Objective: Examine relationships in adrenal and sex hormones in 252 peripubertal girls. Setting and design:...

Primary: To examine the relationship between relative timing of puberty with bone mineral density (BMD) in a group of adolescent girls; Secondary: To determine if family history of breast cancer was associated with bone mineral density. Longitudinal study of girls recruited between 6 and 7 years of age seen every 6 months for 5 years, and subsequen...

To examine the association of breastfeeding or its duration with timing of girls' pubertal onset, and the role of BMI as a mediator in these associations. A population of 1,237 socio-economically and ethnically diverse girls, ages 6-8 years, was recruited across three geographic locations (New York City, Cincinnati, and the San Francisco Bay Area)...

To describe availability and frequency of use of local snack-food outlets and determine whether reported use of these outlets was associated with dietary intakes. Data were cross-sectional. Availability and frequency of use of three types of local snack-food outlets were reported. Daily dietary intakes were based on the average of up to four 24 h d...

Does phthalate exposure during early childhood alter the timing of pubertal development in girls? Urinary concentrations of high-molecular weight phthalate (high-MWP) metabolites are associated with later pubarche. Phthalates are anti-androgenic environmental agents known to alter early development, with possible effects on pubertal onset. This mul...

Abstract OBJECTIVE: Studies comparing physical activity levels in children with and without asthma have had mixed results. Our objective was to investigate the association between asthma diagnosis and physical activity and to examine differences in these associations by race/ethnicity, weight status and caregiver education. We investigated the asso...

Background and objectives: There is growing evidence of pubertal maturation occurring at earlier ages, with many studies based on cross-sectional observations. This study examined age at onset of breast development (thelarche), and the impact of BMI and race/ethnicity, in the 3 puberty study sites of the Breast Cancer and the Environment Research...

PFC serum concentrations were measured in 6-8 year-old girls in Greater Cincinnati (GC) (N = 353) and the San Francisco Bay Area (SFBA) (N = 351). PFOA median concentration was lower in the SFBA than GC (5.8 vs. 7.3 ng/mL). In GC, 48/51 girls living in one area had PFOA concentrations above the NHANES 95th percentile for children 12-19 years (8.4 n...

Lignans and flavonols are dietary phytoestrogens found at high concentrations in the Western Diet. They have potential to influence the timing of puberty. We hypothesized that greater consumption of these 2 phytoestrogens would be related to later age at pubertal onset among girls. Pubertal assessment and 24-hour diet recall data were available for...

Early life exposures during times of rapid growth and development are recognized increasingly to impact later life. Epidemiologic studies document an association between exposures at critical windows of susceptibility with outcomes as diverse as childhood and adult obesity, timing of menarche, and risk for hypertension or breast cancer. This articl...

Introduction Puberty is a time of dramatic change, incorporating maturation of cognitive, social and emotional, physiological, and physical realms. Although the “initial” puberty occurs in the perinatal period, with a functioning hypothalamic–pituitary–gonadal (HPG) axis, most define “puberty” as the adolescent puberty. There are several important...

Study objective: To examine whether the known association between early pubertal breast maturation and insulin sensitivity (SI) is mediated by adiposity. Design: Cross-sectional analyses. Setting: Observational study examining the roles of environment, diet, and obesity on puberty. Participants: 379 girls with a mean age, 7.03 years; 62% wer...

Each case presentation in this issue has a lesson to teach. As with the previous volume, contributions were solicited by open invitation on the Society for Adolescent Health and Medicine's listserv, and authors were instructed to submit concise case presentations with a discussion and a limited number of references. Many of the first authors are ph...

Several studies have noted contemporary girls are undergoing pubertal maturation at younger ages. During this same time period many Western nations have experienced an obesity epidemic, prompting investigators and public health officials to consider the association of these 2 events, and if other exposures might impact this relationship. There are...

Adolescent sexual maturation is staged using Tanner criteria assessed by clinicians, parents, or adolescents. The physiology of sexual maturation is driven by gonadal hormones. We investigate Tanner stage progression as a function of increasing gonadal hormone concentration and compare performances of different raters. Fifty-six boys (mean age, 12....

Primiparity has been associated with 3 to 4 mg/dL lower high-density lipoprotein cholesterol concentrations in black and white adult women that persist several years after delivery. To examine the lasting effects of adolescent pregnancy on blood lipids, an early risk factor for future cardiometabolic diseases. The National Heart Lung and Blood Inst...

Teenagers mature along several areas, including social, cognitive, and biologic realms. The biologic changes called “puberty” can be defined by stage, timing, and tempo. The pubertal stage traditionally has been called “Tanner stages”, and more recently as “Sexual Maturity Rating” (SMR). These stages describe changes in breast tissue, pubic hair, a...