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Hormone Research in Paediatrics 2022Spanning from bench to bedside, the history of normal and precocious puberty is characterized by a series of remarkable advances that have illuminated reproductive... (Review)
Review
Spanning from bench to bedside, the history of normal and precocious puberty is characterized by a series of remarkable advances that have illuminated reproductive physiology and profoundly impacted clinical care. Early recognition of the hypothalamic and pituitary control of ovarian and testicular function led to the identification of GnRH as the key driver of pubertal onset. Decades later, discovery of the kisspeptin system further refined our understanding of human reproductive neuroendocrinology. Development of long-acting analogs of GnRH revolutionized the treatment of precocious puberty worldwide and ushered in the current era of an ever-expanding therapeutic armamentarium. Identification of monogenic etiologies of precocious puberty has further illustrated the exquisite complexity that comprises neurosecretory modulation of the hypothalamic GnRH neuron and may well lead to exciting novel targeted therapies.
Topics: Humans; Gonadotropin-Releasing Hormone; Neuroendocrinology; Neurons; Puberty; Puberty, Precocious
PubMed: 36446322
DOI: 10.1159/000526464 -
Indian Journal of Pediatrics Jun 2023Testicular volume ≥4 ml and appearance of breast budding are the first signs of puberty. Delayed puberty is diagnosed in the absence of thelarche by 13 y or... (Review)
Review
Testicular volume ≥4 ml and appearance of breast budding are the first signs of puberty. Delayed puberty is diagnosed in the absence of thelarche by 13 y or menarche by 15 y in girls and absence of testicular enlargement by 14 y in boys. Delayed puberty can be due to hypogonadotrophic hypogonadism, hypergonadotrophic hypogonadism or eugonadotrophic eugonadism characterised by low, elevated and normal gonadotrophin levels, respectively. Constitutional Delay of Growth and Puberty (CDGP) and systemic illness should be considered before pathological causes. Assessment of sexual maturity by Tanner's staging and anthropometric assessment on growth chart is pivotal. Lack of menarche in girls with thelarche suggests structural abnormalities of reproductive tract or disorders of sexual development. Measurement of bone age helps to interpret hormone measurements and decide on timing of pubertal induction. Ultrasound assessment of abdomen gives valuable clues to pubertal onset (in girls) and possible underlying etiology. Karyotyping is mandatory in all girls with delayed puberty and short stature, and delayed menarche and boys with hypergonadotrophic hypogonadism. Gonadotrophin releasing hormone analogue stimulation test may help distinguish hypogonadotrophic hypogonadism from CDGP. Pubertal induction is done with intramuscular testosterone and oral estradiol in boys and girls, respectively. Hormone replacement is begun at low doses and slowly escalated over 2 y to mimic a physiological puberty process. Short course of testosterone for 3 to 6 mo is helpful in adolescent boys with CDGP and psychological distress. Attainment of adult sexual maturity by 18 y is mandatory to rule out disorders of hypothalamic pituitary gonadal axis.
Topics: Male; Female; Adult; Adolescent; Humans; Puberty, Delayed; Hypogonadism; Testosterone; Puberty; Menarche
PubMed: 37127825
DOI: 10.1007/s12098-023-04577-x -
British Journal of Nursing (Mark Allen... Mar 2021This article provides a brief overview of adolescence. It highlights the key physical changes related to puberty and identifies the latest understanding of neurological... (Review)
Review
This article provides a brief overview of adolescence. It highlights the key physical changes related to puberty and identifies the latest understanding of neurological development in young people. It is also recognised, within the article, that this period of rapid change can have an impact on social and emotional wellbeing. There are conditions that typically have an onset during adolescence, examples of this are offered. The term 'adolescence' is used to describe the stage of development and growth and 'young people' is used throughout to refer to the individuals.
Topics: Adolescent; Humans; Physical Examination; Puberty
PubMed: 33733842
DOI: 10.12968/bjon.2021.30.5.272 -
Minerva Pediatrica Dec 2020Precocious puberty (PP) is a common reason for referral to pediatric endocrinology clinics, with a strong female predominance. PP is a broad term encompassing benign... (Review)
Review
Precocious puberty (PP) is a common reason for referral to pediatric endocrinology clinics, with a strong female predominance. PP is a broad term encompassing benign variants of normal development, gonadotropin-dependent precious puberty (GDPP), and gonadotropin-independent precocious puberty (GIPP). This article reviews the definitions, physiology, clinical presentation, evaluation and treatment of these conditions.
Topics: Child; Female; Gonads; Humans; Hypothalamo-Hypophyseal System; Male; Puberty; Puberty, Precocious; Sex Factors
PubMed: 32748611
DOI: 10.23736/S0026-4946.20.05970-8 -
Minerva Pediatrica Dec 2020The onset of puberty may be late - in the latter part of the predicted normal range or truly delayed - beyond this range. The latest age to start is usually regarded as... (Review)
Review
The onset of puberty may be late - in the latter part of the predicted normal range or truly delayed - beyond this range. The latest age to start is usually regarded as 13 years in girls and 14 years in boys. There may also be a delayed completion of puberty, 16 years in girls and 17 years in boys. The initial approach requires a detailed history and clinical examination to exclude other medical or psychological problems. The presence or absence or pubertal signs should be documented. Investigations should be targeted at ruling out any medical causes and determining whether the delay is due to central gonadotropin deficiency (hypogonadotropic hypogonadism) or a gonadal disorder (hypergonadotropic hypogonadism). Physiological or constitutional delay of growth and puberty (CDGP) is more common in boys but is a diagnosis of exclusion. Current research suggests that CDGP and congenital hypogonadotropic hypogonadism have distinct genetic profiles which may aid in the differential diagnosis. Treatment may be given using low doses of sex steroids, testosterone or estradiol initially in a short course of 3-6 months but continuing in escalating doses mimicking the normal course of puberty, watching regularly for the spontaneous resumption of progress and gonadotropin secretion. In gonadotropin deficiency, sex hormone treatment needs to be continued until completion of pubertal development and growth. Counselling, reassurance and support are key elements in the management of adolescents with delayed puberty.
Topics: Adolescent; Adrenarche; Female; Gonadotropins; Growth Disorders; Humans; Hypogonadism; Male; Menarche; Puberty; Puberty, Delayed; Sex Factors
PubMed: 32748610
DOI: 10.23736/S0026-4946.20.05968-X -
Molecular and Cellular Endocrinology Jan 2021Puberty is a complex process that culminates in the acquisition of psychophysical maturity and reproductive capacity. This elaborate and fascinating process marks the... (Review)
Review
Puberty is a complex process that culminates in the acquisition of psychophysical maturity and reproductive capacity. This elaborate and fascinating process marks the end of childhood. Behind it lies a complex, genetically mediated neuroendocrine mechanism through which the gonads are activated thanks to the fine balance between central inhibitory and stimulating neuromodulators and hormones with both central and peripheral action. The onset of puberty involves the reactivation of the hypothalamic-pituitary-gonadal (HPG) axis, supported by the initial "kiss" between kisspeptin and the hypothalamic neurons that secrete GnRH (the GnRH "pulse generator"). This pulsatile production of GnRH is followed by a rise in LH and, consequently, in gonadal steroids. The onset of puberty varies naturally between individuals, and especially between males and females, in the latter of whom it is typically earlier. However, pathological variations, namely precocious and delayed puberty, are also possible. This article reviews the scientific literature on the physiological mechanisms of puberty and the main pathophysiological aspects of its onset.
Topics: Animals; Endocrine Disruptors; Gonadotropin-Releasing Hormone; Gonads; Humans; Hypothalamo-Hypophyseal System; Neurotransmitter Agents; Puberty
PubMed: 33271219
DOI: 10.1016/j.mce.2020.111094 -
Sexual Development : Genetics,... 2022Puberty is a complex transitional phase in which reproductive capacity is achieved. There is a very wide variation in the age range of the onset of puberty, which... (Review)
Review
Puberty is a complex transitional phase in which reproductive capacity is achieved. There is a very wide variation in the age range of the onset of puberty, which follows a familial, ethnic, and sex pattern. The hypothalamic-pituitary-gonadal axis and several genetic, environmental, and nutritional factors play an important role in the onset of and throughout puberty. Recently, there has been significant progress in identifying factors that affect normal pubertal timing. Different studies have identified single nucleotide polymorphisms (SNPs) that affect pubertal timing in both sexes and across ethnic groups. Single genes are implicated in both precocious and delayed puberty, and epigenetic mechanisms have been suggested to affect the development and function of the GnRH neuronal network and responsiveness of end organs. All these factors can influence normal puberty timing, precocious puberty, and delayed puberty. The objective of this review is to describe recent findings related to the genetic and epigenetic control of puberty and highlight the need to deepen the knowledge of the regulatory mechanisms of this process in the normal and abnormal context.
Topics: Epigenesis, Genetic; Female; Gonadotropin-Releasing Hormone; Humans; Male; Puberty; Puberty, Precocious
PubMed: 34649256
DOI: 10.1159/000519039 -
Frontiers in Endocrinology 2022Puberty is a critical phase of life associated with physiological changes related to sexual maturation, and represents a complex process regulated by multiple endocrine... (Review)
Review
Puberty is a critical phase of life associated with physiological changes related to sexual maturation, and represents a complex process regulated by multiple endocrine and genetic controls. Puberty is driven by hormones, and it can impact the gut microbiome (GM). GM differences between sex emerge at puberty onset, confirming a relationship between microbiota and sex hormones. In this narrative review, we present an overview of precocious pubertal development and the changes in the GM in precocious puberty (PP) in order to consider the role of the sex hormone-gut microbiome axis from the perspective of pediatric endocrinology. Bidirectional interactions between the GM and sex hormones have been proposed in different studies. Although the evidence on the interaction between microbiota and sex hormones remains limited in pediatric patients, the evidence that GM alterations may occur in girls with central precocious puberty (CPP) represents an interesting finding for the prediction and prevention of PP. Deepening the understanding of the connection between the sex hormones and the role of microbiota changes can lead to the implementation of microbiota-targeted therapies in pubertal disorders by offering a pediatric endocrinology perspective.
Topics: Female; Humans; Child; Puberty, Precocious; Gastrointestinal Microbiome; Gonadal Steroid Hormones; Puberty; Microbiota
PubMed: 36339428
DOI: 10.3389/fendo.2022.1000919 -
European Journal of Endocrinology May 2021Puberty is the period of transition from childhood to adulthood characterized by the attainment of adult height and body composition, accrual of bone strength and the... (Review)
Review
Puberty is the period of transition from childhood to adulthood characterized by the attainment of adult height and body composition, accrual of bone strength and the acquisition of secondary sexual characteristics, psychosocial maturation and reproductive capacity. In girls, menarche is a late marker of puberty. Primary amenorrhea is defined as the absence of menarche in ≥ 15-year-old females with developed secondary sexual characteristics and normal growth or in ≥13-year-old females without signs of pubertal development. Furthermore, evaluation for primary amenorrhea should be considered in the absence of menarche 3 years after thelarche (start of breast development) or 5 years after thelarche, if that occurred before the age of 10 years. A variety of disorders in the hypothalamus-pituitary-ovarian axis can lead to primary amenorrhea with delayed, arrested or normal pubertal development. Etiologies can be categorized as hypothalamic or pituitary disorders causing hypogonadotropic hypogonadism, gonadal disorders causing hypergonadotropic hypogonadism, disorders of other endocrine glands, and congenital utero-vaginal anomalies. This article gives a comprehensive review of the etiologies, diagnostics and management of primary amenorrhea from the perspective of pediatric endocrinologists and gynecologists. The goals of treatment vary depending on both the etiology and the patient; with timely etiological diagnostics fertility may be attained even in those situations where no curable treatment exists.
Topics: Amenorrhea; Female; Humans; Hypothalamo-Hypophyseal System; Ovary; Puberty; Puberty, Delayed
PubMed: 33687345
DOI: 10.1530/EJE-20-1487 -
Clinical Endocrinology Oct 2021Central precocious puberty (CPP) results from early activation of the hypothalamic-pituitary-gonadal (HPG) axis. The current state of knowledge of the complex neural... (Review)
Review
Central precocious puberty (CPP) results from early activation of the hypothalamic-pituitary-gonadal (HPG) axis. The current state of knowledge of the complex neural network acting at the level of the hypothalamus and the GnRH neuron to control puberty onset has expanded, particularly in the context of molecular interactions. Along with these advances, the knowledge of pubertal physiology and pathophysiology has also increased. This review focuses on regulatory abnormalities occurring at the hypothalamic level of the HPG axis to cause CPP. The clinical approach to diagnosis of puberty and pubertal disorders is also reviewed, with a particular focus on aetiologies of CPP. The recent identification of mutations in MKRN3 and DLK1 in familial as well sporadic forms of CPP has changed the state of the art of the approach to patients with CPP. Genetic advances have also had important repercussions beyond consideration of puberty alone. Syndromic disorders and central nervous system lesions associated with CPP are also discussed. If untreated, these conditions may lead to adverse physical, psychosocial and medical outcomes.
Topics: Gonadotropin-Releasing Hormone; Humans; Mutation; Puberty; Puberty, Precocious; Ubiquitin-Protein Ligases
PubMed: 33797780
DOI: 10.1111/cen.14475