Frank M. Biro

Defining the Boundaries of Early Adolescence: A User's Guide to Assessing Pubertal Status and Pubertal Timing in Research with Adolescents.

This article addresses pragmatic issues regarding the assessment of puberty in research on adolescent health and development. Because pubertal processes have a major effect on physical, psychological, and social development, we posit that the assessment of pubertal status is at least as important as the specification of age for characterizing adolescent participants in research studies. Yet, a sampling of recent literature shows that the majority of publications addressing health and developmental issues in adolescence lack any measure of puberty. A more comprehensive review of 447 articles reporting to have assessed puberty reveals considerable inconsistencies in methods, definitions, and conceptualizations of puberty and its stages, which highlights the need for better standardization. This article provides an in-depth review of existing methods to assess pubertal status and timing and enumerates the relative merits and shortcomings of several approaches. Conceptual and practical guidelines are provided for selecting specific measures to assess puberty with an emphasis placed on the need for these choices to be driven by the specific goals of the research.

Pubertal Assessment Method and Baseline Characteristics in a Mixed Longitudinal Study of Girls

OBJECTIVES: The objective of this study was to describe the assessment methods and maturation status for a multisite cohort of girls at baseline recruitment and at ages 7 and 8 years. METHODS: The method for pubertal maturation staging was developed collaboratively across 3 sites. Girls at ages 6 to 8 years were recruited at 3 sites: East Harlem, New York; greater Cincinnati metropolitan area; and San Francisco Bay area, California. Baseline characteristics were obtained through interviews with caregivers and anthropometric measurements by trained examiners; breast stage 2 was defined as onset of pubertal maturation. The κ statistic was used to evaluate agreement between master trainers and examiners. Logistic regression models were used to identify factors that are associated with pubertal maturation and linear regression models to examine factors that are associated with height velocity. RESULTS: The baseline cohort included 1239 girls. The proportion of girls who had attained breast stage 2 varied by age, race/ethnicity, BMI percentile, and site. At 7 years, 10.4% of white, 23.4% of black non-Hispanic, and 14.9% of Hispanic girls had attained breast stage ≥2; at 8 years, 18.3%, 42.9%, and 30.9%, respectively, had attained breast stage ≥2. The prime determinant of height velocity was pubertal status. CONCLUSIONS: In this multisite study, there was substantial agreement regarding pubertal staging between examiners across sites. The proportion of girls who had breast development at ages 7 and 8 years, particularly among white girls, is greater than that reported from studies of girls who were born 10 to 30 years earlier.

Overweight, fat patterning, and cardiovascular disease risk factors in black and white boys.

PURPOSE To evaluate the relationships of overweight and fat patterning with cardiovascular disease (CVD) risk factors in black and white boys. DESIGN Cross-sectional analysis of CVD risk factors by weight and central adiposity groups in black and white boys, aged 10 to 15 years. Mean adiposity, lipid, and blood pressure variables were compared between weight and central adiposity groups within race by using linear regression models. Observed clustering of risk factors within weight and adiposity groups was compared with the expected clustering under an assumption of no association. RESULTS Within each racial group, overweight boys had greater skinfolds, lower high-density lipoprotein cholesterol levels, higher low-density lipoprotein cholesterol and triglyceride levels, and higher systolic and diastolic blood pressure than non-overweight boys. Among overweight boys, greater central adiposity was associated with higher risk factor levels and increased clustering of risk factors. CONCLUSION Overweight and central adiposity together profoundly affect CVD risk factor levels and risk factor clustering in black and white boys.

Investigation of Relationships between Urinary Biomarkers of Phytoestrogens, Phthalates, and Phenols and Pubertal Stages in Girls

Background Hormonally active environmental agents may alter the course of pubertal development in girls, which is controlled by steroids and gonadotropins. Objectives We investigated associations of concurrent exposures from three chemical classes (phenols, phthalates, and phytoestrogens) with pubertal stages in a multiethnic longitudinal study of 1,151 girls from New York City, New York, greater Cincinnati, Ohio, and northern California who were 6–8 years of age at enrollment (2004–2007). Methods We measured urinary exposure biomarkers at visit 1 and examined associations with breast and pubic hair development (present or absent, assessed 1 year later) using multivariate adjusted prevalence ratios (PR) and 95% confidence intervals (CIs). Modification of biomarker associations by age-specific body mass index percentile (BMI%) was investigated, because adipose tissue is a source of peripubertal hormones. Results Breast development was present in 30% of girls, and 22% had pubic hair. High-molecular-weight phthalate (high MWP) metabolites were weakly associated with pubic hair development [adjusted PR, 0.94 (95% CI, 0.88–1.00), fifth vs. first quintile]. Small inverse associations were seen for daidzein with breast stage and for triclosan and high MWP with pubic hair stage; a positive trend was observed for low-molecular-weight phthalate biomarkers with breast and pubic hair development. Enterolactone attenuated BMI associations with breast development. In the first enterolactone quintile, for the association of high BMI with any development, the PR was 1.34 (95% CI, 1.23–1.45 vs. low BMI). There was no BMI association in the fifth, highest quintile of enterolactone. Conclusions Weak hormonally active xenobiotic agents investigated in this study had small associations with pubertal development, mainly among those agents detected at highest concentrations.

Acne vulgaris in premenarchal girls : an early sign of puberty associated with rising levels of dehydroepiandrosterone

BACKGROUND This study examined the relationships of pubertal maturation and sex steroid hormones to the development of acne in young girls. Black (n = 317) and white (n = 306) premenarchal girls with a mean age of 9.97 +/- 0.62 years were evaluated for acne prevalence and severity, pubic hair and areolar maturation, and sex steroid hormone levels. RESULTS Overall, 77.8% of the girls had some acne; of the whole group, 48.3% had only comedonal acne, 2.2% had only inflammatory acne, and 27.3% had both types. Although black girls matured at an earlier age than white girls, racial differences in acne were minimal when adjusted for pubertal maturation. Acne increased with advancing maturation; at Tanner pubic hair stages 1, 2, and 3, the prevalence of acne rose from 73.1% to 84.0% and to 90.6%, respectively. Acne lesion counts at seven facial locations revealed a predominance of midfacial acne on the middle aspect of the forehead, nose, and chin. Sex steroid hormone levels measured in 365 of the girls were found to increase significantly during maturation from prepuberty to early puberty. Testosterone-estrogen-binding globulin and the ratio of testosterone to estradiol decreased. In 118 prepubertal girls, estradiol, total and free testosterone, progesterone, testosterone to estradiol ratio, and testosterone-estrogen-binding globulin levels were no different whether in subjects with acne or without acne. However, the level of dehydroepiandrosterone sulfate, an androgen of adrenal origin, was significantly higher in prepubertal girls with acne. CONCLUSION Acne, especially the comedonal type, can be the first sign of pubertal maturation in girls, even preceding pubic hair and areolar development. Concentration of dehydroepiandrosterone sulfate is significantly and specifically associated with the initiation of acne in young girls.

Pubertal staging in boys

To determine the earliest signs of pubertal maturation, we followed 515 boys, aged 10 to 15 years at intake, every 6 months for 3 years. Changes in age, height, weight, body mass index, and serum levels of sex steroid hormones were significantly related to pubertal stage (PS). The earliest clinical stage of pubertal maturation, designated PS2a, was represented by the absence of public hair and a testicular volume 3 cc or greater; 6 months later, further maturation had occurred in 82% of these boys. Inclusion of PS2a as the earliest stage of puberty may help allay concerns about boys with perceived delayed maturation, and may allow more precise definition of early puberty.

Supplementation with omega-3 polyunsaturated fatty acids in the management of dysmenorrhea in adolescents

OBJECTIVES The purpose of the study was to examine whether dietary supplementation with omega-3 fatty acids can relieve symptoms of dysmenorrhea in adolescents. STUDY DESIGN Forty-two adolescents with dysmenorrhea were randomly allocated to two groups. In the first group 21 girls received fish oil (1080 mg icosapentaenoic acid, 720 mg docosahexaenoic acid, and 1.5 mg vitamin E) daily for 2 months followed by a placebo for an additional 2 months. In the second group 21 girls received placebo for the first 2 months, followed by fish oil for 2 more months. The Cox Menstrual Symptom Scale was used to assess response to treatment. RESULTS There were no significant differences in the Cox Menstrual Symptom Scale between the two groups at baseline after 2 months of placebo administration. After 2 months of treatment with fish oil there was a marked reduction in the Cox Menstrual Symptom Scale from a baseline mean value of 69.9 to 44.0 (p < 0.0004). CONCLUSIONS This study suggests that dietary supplementation with omega-3 fatty acids has a beneficial effect on symptoms of dysmenorrhea in adolescents.

Sexual maturation and obesity in 9- and 10-year-old black and white girls: The National Heart, Lung, and Blood Institute Growth and Health Study

OBJECTIVE To assess the relationship between pubertal maturation and obesity in 9- and 10-year-old black and white girls. METHOD Cross-sectional analysis of cohort baseline data. SUBJECTS A cohort of 2379 girls recruited from selected schools in Richmond, Calif., and greater Cincinnati, Ohio, and from the membership rolls of a prepaid group practice in greater Washington, D.C. RESULTS Sixty-four percent of black girls had begun pubertal maturation compared with 33% of white girls. In prepubertal girls, racial differences in height, weight, body mass index (kilograms per square meter) and skin-fold thickness were not significant. Within each race, onset of pubertal maturation was associated with greater height, weight, body mass index, and skin-fold measurements. Within 9-year-old girls who had begun pubertal maturation but not reached menarche, black girls were taller and heavier than white girls. Among pubertal but premenarcheal 10-year-old subjects, black girls were taller and heavier and had greater body mass index and subscapular skin-fold values. After analyses were adjusted for pubertal maturation stage by means of pubic hair development, 10-year-old pubertal black girls remained taller and heavier, but racial differences in body mass index and the sum of skin-fold measurements ceased to be significant. CONCLUSIONS These findings suggest that the initiation of racial differences in obesity are related, at least temporally, to pubertal maturation.

Onset of Breast Development in a Longitudinal Cohort

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 Program, a prospective cohort of >1200 girls. METHODS: Girls, 6 to 8 years at enrollment, were followed longitudinally at regular intervals from 2004 to 2011 in 3 geographic areas: the San Francisco Bay Area, Greater Cincinnati, and New York City. Sexual maturity assessment using Tanner staging was conducted by using standardized observation and palpation methods by trained and certified staff. Kaplan-Meier analyses were used to describe age at onset of breast maturation by covariates. RESULTS: The age at onset of breast stage 2 varied by race/ethnicity, BMI at baseline, and site. Median age at onset of breast stage 2 was 8.8, 9.3, 9.7, and 9.7 years for African American, Hispanic, white non-Hispanic, and Asian participants, respectively. Girls with greater BMI reached breast stage 2 at younger ages. Age-specific and standardized prevalence of breast maturation was contrasted to observations in 2 large cross-sectional studies conducted 10 to 20 years earlier (Pediatric Research in Office Settings and National Health and Nutrition Examination Survey III) and found to have occurred earlier among white, non-Hispanic, but not African American girls. CONCLUSIONS: We observed the onset of thelarche at younger ages than previously documented, with important differences associated with race/ethnicity and BMI, confirming and extending patterns seen previously. These findings are consistent with temporal changes in BMI.

Predictors of severity of acne vulgaris in young adolescent girls: Results of a five-year longitudinal study

OBJECTIVES The objectives of this study were to determine which factors in early pubertal girls might be predictive of later, severe facial acne. STUDY DESIGN The study was a 5-year longitudinal cohort study, with yearly visits from 1987 through 1991, in a volunteer sample of 439 black and 432 white fourth- and fifth-grade girls with consent from their legal guardians. The subjects were recruited from public and parochial schools in Cincinnati, Ohio. The degree of facial acne was classified annually as mild, moderate, or severe. Blood samples were obtained at the first, third, and fifth years of the study. Using the acne status during the fifth year of the study as the outcome variable, we determined the contributions from the prior acne status and the serum levels of dehydroepiandrosterone sulfate (DHEAS), testosterone, free testosterone (FT), estradiol (E2), progesterone, and testosterone-estrogen binding globulin (TEBG) and compared the results at various ages and at times before and after menarche. RESULTS No racial differences in acne or hormone levels were found. There was a progressive increase in the number of acne lesions with age and maturation. The girls exhibited many more comedonal than inflammatory acne lesions, regardless of age. The girls in whom severe acne developed by the fifth year of the study had significantly more comedones and inflammatory lesions than girls with mild or moderate acne, as early as age 10 years, approximately 2 h years before menarche, a time when their degree of acne was mild. Girls with mild comedonal acne had significantly later onset of menarche (12.5 compared with 12.2 years) than girls with severe comedonal acne. Girls in whom severe comedonal acne developed had significantly higher levels of serum DHEAS and, in a longitudinal analysis, somewhat higher levels of testosterone and FT in comparison with girls who had mild or moderate comedonal acne. Serum E2, testosterone/E2, progesterone, and TEBG values were no different in girls with severe compared with mild or moderate comedonal acne. CONCLUSIONS The early development of comedonal acne may be one of the best predictors of later, more severe disease. The adrenal hormone DHEAS appears to play an important role in the initiation of acne. DHEAS, testosterone, and FT are associated with the perpetuation of severe comedonal acne. Early recognition of young girls at risk of having severe comedonal acne may enable the clinician to intervene and thus prevent unwanted sequelae.