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Journal ArticleDOI

Onset of breast development in a longitudinal cohort.

TL;DR: The onset of thelarche was observed at younger ages than previously documented, with important differences associated with race/ethnicity and BMI, confirming and extending patterns seen previously.
Abstract: 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.
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Journal ArticleDOI
TL;DR: A timely diagnosis and treatment to induce puberty can be beneficial for sexual, bone and metabolic health, and might help minimize some the psychological effects of CHH.
Abstract: Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder caused by the deficient production, secretion or action of gonadotropin-releasing hormone (GnRH), which is the master hormone regulating the reproductive axis. CHH is clinically and genetically heterogeneous, with >25 different causal genes identified to date. Clinically, the disorder is characterized by an absence of puberty and infertility. The association of CHH with a defective sense of smell (anosmia or hyposmia), which is found in ∼50% of patients with CHH is termed Kallmann syndrome and results from incomplete embryonic migration of GnRH-synthesizing neurons. CHH can be challenging to diagnose, particularly when attempting to differentiate it from constitutional delay of puberty. A timely diagnosis and treatment to induce puberty can be beneficial for sexual, bone and metabolic health, and might help minimize some of the psychological effects of CHH. In most cases, fertility can be induced using specialized treatment regimens and several predictors of outcome have been identified. Patients typically require lifelong treatment, yet ∼10-20% of patients exhibit a spontaneous recovery of reproductive function. This Consensus Statement summarizes approaches for the diagnosis and treatment of CHH and discusses important unanswered questions in the field.

590 citations

Journal ArticleDOI
TL;DR: It is argued that nicotine exposure, increasingly occurring as a result of e‐cigarette use, may induce epigenetic changes that sensitize the brain to other drugs and prime it for future substance abuse.
Abstract: Adolescence encompasses a sensitive developmental period of enhanced clinical vulnerability to nicotine, tobacco, and e-cigarettes. While there are sociocultural influences, data at preclinical and clinical levels indicate that this adolescent sensitivity has strong neurobiological underpinnings. Although definitions of adolescence vary, the hallmark of this period is a profound reorganization of brain regions necessary for mature cognitive and executive function, working memory, reward processing, emotional regulation, and motivated behavior. Regulating critical facets of brain maturation are nicotinic acetylcholine receptors (nAChRs). However, perturbations of cholinergic systems during this time with nicotine, via tobacco or e-cigarettes, have unique consequences on adolescent development. In this review, we highlight recent clinical and preclinical data examining the adolescent brain's distinct neurobiology and unique sensitivity to nicotine. First, we discuss what defines adolescence before reviewing normative structural and neurochemical alterations that persist until early adulthood, with an emphasis on dopaminergic systems. We review how acute exposure to nicotine impacts brain development and how drug responses differ from those seen in adults. Finally, we discuss the persistent alterations in neuronal signaling and cognitive function that result from chronic nicotine exposure, while highlighting a low dose, semi-chronic exposure paradigm that may better model adolescent tobacco use. We argue that nicotine exposure, increasingly occurring as a result of e-cigarette use, may induce epigenetic changes that sensitize the brain to other drugs and prime it for future substance abuse.

327 citations


Cites background from "Onset of breast development in a lo..."

  • ...The underlying causes remain unclear although some suggest higher rates of obesity (Biro et al. 2013) while others suggest epigenetic and environmental influences (Aksglaede et al. 2009; Meeker, 2012; Hagen et al. 2014) as the main contributing factors....

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  • ...Furthermore, there is growing evidence that sexual maturation is occurring progressively earlier in the US and some European countries (Euling et al. 2008; Aksglaede et al. 2009; Biro et al. 2013; Cabrera et al. 2014)....

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Journal ArticleDOI
TL;DR: Current challenges involving the precise diagnosis and adequate treatment of central precocious puberty are described, which remain challenging for paediatric endocrinologists.

261 citations

Journal ArticleDOI
TL;DR: This review is a comprehensive synthesis of the current literature available regarding the diagnosis, patient management, and genetic foundations of CHH relative to normal reproductive development.
Abstract: The initiation and maintenance of reproductive capacity in humans is dependent on pulsatile secretion of the hypothalamic hormone GnRH. Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder that results from the failure of the normal episodic GnRH secretion, leading to delayed puberty and infertility. CHH can be associated with an absent sense of smell, also termed Kallmann syndrome, or with other anomalies. CHH is characterized by rich genetic heterogeneity, with mutations in >30 genes identified to date acting either alone or in combination. CHH can be challenging to diagnose, particularly in early adolescence where the clinical picture mirrors that of constitutional delay of growth and puberty. Timely diagnosis and treatment will induce puberty, leading to improved sexual, bone, metabolic, and psychological health. In most cases, patients require lifelong treatment, yet a notable portion of male patients (∼10% to 20%) exhibit a spontaneous recovery of their reproductive function. Finally, fertility can be induced with pulsatile GnRH treatment or gonadotropin regimens in most patients. In summary, this review is a comprehensive synthesis of the current literature available regarding the diagnosis, patient management, and genetic foundations of CHH relative to normal reproductive development.

208 citations

Journal ArticleDOI
TL;DR: 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.
Abstract: 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.

176 citations

References
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Journal ArticleDOI
TL;DR: The extent of normal individual variation observed in the events of puberty among the girls of the Harpenden Growth Study is described.
Abstract: In Great Britain some girls begin to menstruate in their 10th or 11th years, while others who are equally healthy may not experience menarche until they 'are 14, 15, or even older. Menarche is, however, only a single event in the combination of physical changes which constitute puberty. The adolescent growth spurt, the development of the breasts, and the growth of the pubic hair occur more or less concurrently, and take, on the average, about 3 years from beginning to completion, with menarche occurring usually in the latter half of this period (Tanner, 1962). At present we lack detailed information about the rate at which girls progress through the stages of puberty and about the relation of one event to another. Only longitudinal studies (i.e. studies in which the same individuals are examined repeatedly over a period of time) can provide this information, which would be helpful both to the clinician in distinguishing the normal from the abnormal, and to the neuro-endocrinologist in constructing hypotheses about the mechanisms by which puberty is controlled. Present knowledge is based on studies carried out on small numbers of children in the United States a generation ago, together with some German studies of a similar period (for literature see Tanner, 1962). The only recent European study in which the events of puberty have been followed longitudinally is the Harpenden Growth Study, which began 19 years ago in England and is still in progress. Anthropometric measurements have been taken, and the development of the breasts and pubic hair have been recorded photographically at 3monthly intervals throughout puberty. Though these data may be subject to certain biases, discussed below, they provide information available from no other source. This paper describes the extent of normal individual variation observed in the events of puberty among the girls of the Harpenden Growth Study. We discuss: (a) variation in the chrono-

5,078 citations

Journal ArticleDOI
TL;DR: Assessment of the strength of associations between BMI and different sites of cancer and differences in these associations between sex and ethnic groups should inform the exploration of biological mechanisms that link obesity with cancer.

4,504 citations

Journal ArticleDOI
01 Feb 2012-JAMA
TL;DR: The most recent estimates of obesity prevalence in US children and adolescents for 2009-2010 are presented and trend analyses over a 12-year period indicated a significant increase in obesity prevalence between 1999-2000 and 2009- 2010 in males aged 2 through 19 years but not in females.
Abstract: Context: The prevalence of childhood obesity increased in the 1980s and 1990s but there were no significant changes in prevalence between 1999-2000 and 2007-2008 in the United States.

3,941 citations

Journal ArticleDOI
28 May 2008-JAMA
TL;DR: The prevalence of high BMI for age among children and adolescents showed no significant changes between 2003-2004 and 2005-2006 and no significant trends between 1999 and 2006.
Abstract: This study aims to estimate the prevalence of 3 measures of high body mass index (BMI) for age and to examine recent trends for US children and adolescents using national data with measured heights and weights. Height and weight measurements were obtained from 8165 children and adolescents as part of the 2003-2004 and 2005-2006 National Health and Nutrition Examination Survey (NHANES), nationally representative surveys of the US civilian, noninstitutionalized population. The main outcome measures were the prevalence of BMI for age at or above the 97th percentile, at or above the 95th percentile, and at or above the 85th percentile of the 2000 sex-specific Centers for Disease Control and Prevention (CDC) BMI-for-age growth charts among US children by age, sex, and racial/ethnic group. As no statistically significant differences in the prevalence of high BMI for age were found between estimates for 2003-2004 and 2005-2006, data for the 4 years were combined to provide more stable estimates for the most recent time period. Overall, in 2003-2006, 11.3% of children and adolescents aged 2-19 years were at or above the 97th percentile of the 2000 BMI-for-age growth charts, 16.3% were at or above the 95th percentile, and 31.9% were at or above the 85th percentile. Prevalence estimates varied by age and by racial/ethnic group. Analyses of the trends in high BMI for age showed no statistically significant trend over the 4 time periods (1999-2000, 2001-2002, 2003-2004, and 2005-2006) for either boys or girls.

1,848 citations

Journal ArticleDOI
TL;DR: The extent of normal individual variation observed in the events of puberty among the girls of the Harpenden Growth Study is described.
Abstract: In Great Britain some girls begin to menstruate in their 10th or 11th years, while others who are equally healthy may not experience menarche until they 'are 14, 15, or even older. Menarche is, however, only a single event in the combination of physical changes which constitute puberty. The adolescent growth spurt, the development of the breasts, and the growth of the pubic hair occur more or less concurrently, and take, on the average, about 3 years from beginning to completion, with menarche occurring usually in the latter half of this period (Tanner, 1962). At present we lack detailed information about the rate at which girls progress through the stages of puberty and about the relation of one event to another. Only longitudinal studies (i.e. studies in which the same individuals are examined repeatedly over a period of time) can provide this information, which would be helpful both to the clinician in distinguishing the normal from the abnormal, and to the neuro-endocrinologist in constructing hypotheses about the mechanisms by which puberty is controlled. Present knowledge is based on studies carried out on small numbers of children in the United States a generation ago, together with some German studies of a similar period (for literature see Tanner, 1962). The only recent European study in which the events of puberty have been followed longitudinally is the Harpenden Growth Study, which began 19 years ago in England and is still in progress. Anthropometric measurements have been taken, and the development of the breasts and pubic hair have been recorded photographically at 3monthly intervals throughout puberty. Though these data may be subject to certain biases, discussed below, they provide information available from no other source. This paper describes the extent of normal individual variation observed in the events of puberty among the girls of the Harpenden Growth Study. We discuss: (a) variation in the chrono-

1,649 citations


Additional excerpts

  • ...8) Race/Ethnicity Black 168 40 127 34 96 22 391 32 Asian 0 0 5 1 52 12 57 5 Hispanic 248 60 15 4 108 24 371 30 White 0 0 232 61 188 42 420 34 Education of family provider Grade School (1-8), Some High School (9-11) or High School Diploma/GED 232 58 35 10 83 20 350 31...

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