-
European Journal of Endocrinology Oct 2020Pubertal timing is regulated by the complex interplay of genetic, environmental, nutritional and epigenetic factors. Criteria for determining normal pubertal timing, and... (Review)
Review
Pubertal timing is regulated by the complex interplay of genetic, environmental, nutritional and epigenetic factors. Criteria for determining normal pubertal timing, and thus the definition of precocious puberty, have evolved based on published population studies. The significance of the genetic influence on pubertal timing is supported by familial pubertal timing and twin studies. In contrast to the many monogenic causes associated with hypogonadotropic hypogonadism, only four monogenic causes of central precocious puberty (CPP) have been described. Loss-of-function mutations in Makorin Ring Finger Protein 3(MKRN3), a maternally imprinted gene on chromosome 15 within the Prader-Willi syndrome locus, are the most common identified genetic cause of CPP. More recently, several mutations in a second maternally imprinted gene, Delta-like noncanonical Notch ligand 1 (DLK1), have also been associated with CPP. Polymorphisms in both genes have also been associated with the age of menarche in genome-wide association studies. Mutations in the genes encoding kisspeptin (KISS1) and its receptor (KISS1R), potent activators of GnRH secretion, have also been described in association with CPP, but remain rare monogenic causes. CPP has both short- and long-term health implications for children, highlighting the importance of understanding the mechanisms contributing to early puberty. Additionally, given the role of mutations in the imprinted genes MKRN3 and DLK1 in pubertal timing, other imprinted candidate genes should be considered for a role in puberty initiation.
Topics: Adolescent; Child; Female; Genome-Wide Association Study; Genomic Imprinting; Humans; Kisspeptins; Male; Mutation; Puberty; Puberty, Precocious; Receptors, Kisspeptin-1
PubMed: 32698138
DOI: 10.1530/EJE-20-0103 -
Gynecologie, Obstetrique & Fertilite Nov 2016Participation in recreational physical activity is widely acknowledged to provide significant health benefits. Conversely, intense training imposes several constraints,... (Review)
Review
Participation in recreational physical activity is widely acknowledged to provide significant health benefits. Conversely, intense training imposes several constraints, such as intermittent or chronic metabolic and psychogenic training stressors and maintenance of very low body fat to maximize performance. Adolescent and adult athletic women are therefore at risk of overtraining and/or poor dietary intake, which may have several consequences for endocrine function particularly on hypothalamic-pituitary-gonadal axis. Female athletes, particularly those participating in sports needing leanness or low body weight, present a high prevalence of menstrual disorders with clinical manifestations ranging from delayed menarche, oligomenorrhea to primary and secondary amenorrhea. A high degree of variability according to the type of sport and the intensity of the practice is however observed. Exercise-related reproductive dysfunction may have some consequences for growth velocity and peak bone mass acquisition during adolescence and bone pathologies in adults. Recent findings highlight the endocrine role of adipose tissue and energy balance in the regulation of homeostasis and reproductive function. A better understanding of the mechanisms whereby intense training affects the endocrine systems may orient research to develop innovative strategies probably based on individualized nutritional approach to improve the medical care of these female athletes and protect their reproductive function.
Topics: Adolescent; Amenorrhea; Body Composition; Bone Density; Diet; Exercise; Female; Humans; Menarche; Menstruation Disturbances; Puberty; Reproduction; Sports; Young Adult
PubMed: 27751748
DOI: 10.1016/j.gyobfe.2016.09.001 -
International Journal of Molecular... Oct 2022Thousands of natural or manufactured chemicals were defined as endocrine-disrupting chemicals (EDCs) because they can interfere with hormone activity and the endocrine... (Review)
Review
Thousands of natural or manufactured chemicals were defined as endocrine-disrupting chemicals (EDCs) because they can interfere with hormone activity and the endocrine system. We summarize and discuss what we know and what we still need to learn about EDCs' pathogenic mechanisms of action, as well as the effects of the most common EDCs on endocrine system health in childhood. The MEDLINE database (PubMed) was searched on 13 May 2022, filtering for EDCs, endocrine diseases, and children. EDCs are a group of compounds with high heterogeneity, but usually disrupt the endocrine system by mimicking or interfering with natural hormones or interfering with the body's hormonal balance through other mechanisms. Individual EDCs were studied in detail, while humans' "cocktail effect" is still unclear. In utero, early postnatal life, and/or pubertal development are highly susceptible periods to exposure. Human epidemiological studies suggest that EDCs affect prenatal growth, thyroid function, glucose metabolism, obesity, puberty, and fertility through several mechanisms. Further studies are needed to clarify which EDCs can mainly act on epigenetic processes. A better understanding of EDCs' effects on human health is crucial to developing future regulatory strategies to prevent exposure and ensure the health of children today, in future generations, and in the environment.
Topics: Child; Endocrine Disruptors; Endocrine System; Female; Glucose; Hormones; Humans; Pregnancy; Puberty
PubMed: 36233201
DOI: 10.3390/ijms231911899 -
Frontiers in Endocrinology 2023
Topics: Sexual Maturation; Humans; Puberty
PubMed: 37560304
DOI: 10.3389/fendo.2023.1258656 -
JAMA Pediatrics Apr 2020The initial clinical sign of pubertal onset in girls is breast gland development (thelarche). Although numerous studies have used recalled age at menarche (first... (Meta-Analysis)
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.
Topics: Adolescent; Age Factors; Breast; Child; Female; Humans; Puberty
PubMed: 32040143
DOI: 10.1001/jamapediatrics.2019.5881 -
Frontiers in Endocrinology 2024Cryptorchidism is the condition in which one or both testes have not descended adequately into the scrotum. The congenital form of cryptorchidism is one of the most... (Review)
Review
Cryptorchidism is the condition in which one or both testes have not descended adequately into the scrotum. The congenital form of cryptorchidism is one of the most prevalent urogenital anomalies in male newborns. In the acquired form of cryptorchidism, the testis that was previously descended normally is no longer located in the scrotum. Cryptorchidism is associated with an increased risk of infertility and testicular germ cell tumors. However, data on pubertal progression are less well-established because of the limited number of studies. Here, we aim to review the currently available data on pubertal development in boys with a history of non-syndromic cryptorchidism-both congenital and acquired cryptorchidism. The review is focused on the timing of puberty, physical changes, testicular growth, and endocrine development during puberty. The available evidence demonstrated that the timing of the onset of puberty in boys with a history of congenital cryptorchidism does not differ from that of non-cryptorchid boys. Hypothalamic-pituitary-gonadal hormone measurements showed an impaired function or fewer Sertoli cells and/or germ cells among boys with a history of cryptorchidism, particularly with a history of bilateral cryptorchidism treated with orchiopexy. Leydig cell function is generally not affected in boys with a history of cryptorchidism. Data on pubertal development among boys with acquired cryptorchidism are lacking; therefore, more research is needed to investigate pubertal progression among such boys.
Topics: Infant, Newborn; Humans; Male; Cryptorchidism; Testicular Neoplasms; Leydig Cells; Puberty
PubMed: 38532895
DOI: 10.3389/fendo.2024.1347435 -
Pediatrics Feb 2020Gonadotropin-releasing hormone analogues are commonly prescribed to suppress endogenous puberty for transgender adolescents. There are limited data regarding the mental...
BACKGROUND AND OBJECTIVES
Gonadotropin-releasing hormone analogues are commonly prescribed to suppress endogenous puberty for transgender adolescents. There are limited data regarding the mental health benefits of this treatment. Our objective for this study was to examine associations between access to pubertal suppression during adolescence and adult mental health outcomes.
METHODS
Using a cross-sectional survey of 20 619 transgender adults aged 18 to 36 years, we examined self-reported history of pubertal suppression during adolescence. Using multivariable logistic regression, we examined associations between access to pubertal suppression and adult mental health outcomes, including multiple measures of suicidality.
RESULTS
Of the sample, 16.9% reported that they ever wanted pubertal suppression as part of their gender-related care. Their mean age was 23.4 years, and 45.2% were assigned male sex at birth. Of them, 2.5% received pubertal suppression. After adjustment for demographic variables and level of family support for gender identity, those who received treatment with pubertal suppression, when compared with those who wanted pubertal suppression but did not receive it, had lower odds of lifetime suicidal ideation (adjusted odds ratio = 0.3; 95% confidence interval = 0.2-0.6).
CONCLUSIONS
This is the first study in which associations between access to pubertal suppression and suicidality are examined. There is a significant inverse association between treatment with pubertal suppression during adolescence and lifetime suicidal ideation among transgender adults who ever wanted this treatment. These results align with past literature, suggesting that pubertal suppression for transgender adolescents who want this treatment is associated with favorable mental health outcomes.
Topics: Adolescent; Adult; Age Factors; Analysis of Variance; Confidence Intervals; Cross-Sectional Studies; Female; Gender Identity; Gonadotropin-Releasing Hormone; Health Services Accessibility; Humans; Male; Mental Health; Odds Ratio; Puberty; Suicidal Ideation; Surveys and Questionnaires; Transgender Persons; Young Adult
PubMed: 31974216
DOI: 10.1542/peds.2019-1725 -
Nature Nov 2021The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development....
The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.
Topics: Adolescent; Aged, 80 and over; Animals; Child; Child Development; Estrous Cycle; Female; Homozygote; Humans; Hypothalamus; Insulin-Like Growth Factor I; Male; Melanocortins; Menarche; Mice; Nutritional Status; Phenotype; Puberty; Receptor, Melanocortin, Type 3; Sexual Maturation; Time Factors; Weight Gain
PubMed: 34732894
DOI: 10.1038/s41586-021-04088-9 -
Current Opinion in Pediatrics Aug 2018To summarize advances in the genetics underlying variation in normal pubertal timing, precocious puberty, and delayed puberty, and to discuss mechanisms by which genes... (Review)
Review
PURPOSE OF REVIEW
To summarize advances in the genetics underlying variation in normal pubertal timing, precocious puberty, and delayed puberty, and to discuss mechanisms by which genes may regulate pubertal timing.
RECENT FINDINGS
Genome-wide association studies have identified hundreds of loci that affect pubertal timing in the general population in both sexes and across ethnic groups. Single genes have been implicated in both precocious and delayed puberty. Potential mechanisms for how these genetic loci influence pubertal timing may include effects on the development and function of the GnRH neuronal network and the responsiveness of end-organs.
SUMMARY
There has been significant progress in identifying genetic loci that affect normal pubertal timing, and the first single-gene causes of precocious and delayed puberty are being described. How these genes influence pubertal timing remains to be determined.
Topics: Adolescent; Age Factors; Child; Genetic Markers; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Puberty; Puberty, Delayed; Puberty, Precocious
PubMed: 29771761
DOI: 10.1097/MOP.0000000000000642 -
Journal of Cystic Fibrosis : Official... Oct 2019Historically, delayed puberty was considered a common clinical feature of cystic fibrosis (CF). More recent reports have documented normal pubertal progression in the... (Review)
Review
Historically, delayed puberty was considered a common clinical feature of cystic fibrosis (CF). More recent reports have documented normal pubertal progression in the majority of individuals with CF. However, youth with more severe disease are still at risk for delayed puberty. Careful evaluation of pubertal development in children and adolescents with CF is important as pubertal timing impacts linear growth, bone mineral accrual, body image and psychosocial wellbeing, all of which can also be impacted directly by CF. This article reviews the physiology of puberty, timing of puberty in CF, evaluation of pubertal development, and the differential diagnosis, evaluation, and management of delayed and precocious puberty in people with CF.
Topics: Adolescent; Child; Cystic Fibrosis; Diagnosis, Differential; Female; Humans; Male; Puberty; Puberty, Delayed
PubMed: 31679734
DOI: 10.1016/j.jcf.2019.08.013