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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 -
Best Practice & Research. Clinical... Apr 2018Over the past 20 years, a clear secular trend toward the earlier onset of puberty has been described. A better knowledge should help clinicians attempting to define both... (Review)
Review
Over the past 20 years, a clear secular trend toward the earlier onset of puberty has been described. A better knowledge should help clinicians attempting to define both precocious and delayed puberty (PP and DP, respectively). The definition of PP for girls is the appearance of secondary sex characteristics development before the age of 8 years, while DP is based on the absence of thelarche at the age of 13 years. Regarding PP, one should clinically distinguish between true precocious puberty, i.e., complete or central PP, and incomplete PP, which refers to premature thelarche, premature pubarche, and isolated menarche. Evaluation of girls of PP requires careful examination of the clinical expression, a GnRH test, and imaging of the central neurosystem. GnRH analog is considered the gold standard treatment of central precocious puberty. Peripheral PP should be managed according to the underlying causes. DP is suspected in girls with no breast development by the age of 13 years, or absence of menarche at 15 years with secondary sex characteristics. The clinical examination along with endocrine, radiological, and genetic investigation should be able to identify girls with permanent hypogonadism as opposed to those with transitory hypogonadism, who undergo spontaneous but DP. Estrogen therapy should be discussed according to the causes of DP. In all cases, emotional and psychosocial disorders should be considered for these girls with disorders of puberty.
Topics: Adolescent; Child; Female; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Menarche; Puberty, Delayed; Puberty, Precocious
PubMed: 29422239
DOI: 10.1016/j.bpobgyn.2017.11.004 -
American Family Physician Nov 2017Disorders of puberty can profoundly impact physical and psychosocial well-being. Precocious puberty is pubertal onset before eight years of age in girls and before nine... (Review)
Review
Disorders of puberty can profoundly impact physical and psychosocial well-being. Precocious puberty is pubertal onset before eight years of age in girls and before nine years of age in boys. Patients with early isolated pubertal changes, prepubertal linear growth, and no worrisome neurologic symptoms typically have a benign pattern of development and should be monitored in the appropriate clinical context. Among patients with true precocious puberty, or full activation of the hypothalamic-pituitary-gonadal axis, most girls have an idiopathic etiology, whereas it is commonly due to identifiable pathology on imaging in boys. History and physical examination should be followed by measurements of serum follicle-stimulating hormone, luteinizing hormone, and testosterone (boys) or estradiol (girls); thyroid function testing; and bone age radiography. Brain magnetic resonance imaging should be performed in girls younger than six years, all boys with precocious puberty, and children with neurologic symptoms. Delayed puberty is the absence of breast development in girls by 13 years of age and absence of testicular growth to at least 4 mL in volume or 2.5 cm in length in boys by 14 years of age. Constitutional delay of growth and puberty is a common cause of delayed puberty; however, functional or persistent hypogonadism should be excluded. History and physical examination should be followed by measurements of serum follicle-stimulating hormone, luteinizing hormone, and testosterone (boys) or estradiol (girls); and bone age radiography. Abnormal growth velocity necessitates assessment of serum thyroid function, prolactin, and insulinlike growth factor I. Boys 14 years and older and girls 13 years and older may benefit from sex steroid treatment to jump-start puberty. Referral to a pediatric endocrinologist may be warranted after the initial evaluation.
Topics: Adolescent; Age of Onset; Body Height; Child; Estradiol; Female; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Humans; Hypothalamo-Hypophyseal System; Luteinizing Hormone; Male; Menarche; Puberty, Precocious; Sexual Maturation
PubMed: 29094880
DOI: No ID Found -
Best Practice & Research. Clinical... Jun 2019Delayed puberty (DP) affects approximately 2% of adolescents. In the vast majority of patients in both sexes, it is due to constitutional delay of growth and puberty... (Comparative Study)
Comparative Study Review
Delayed puberty (DP) affects approximately 2% of adolescents. In the vast majority of patients in both sexes, it is due to constitutional delay of growth and puberty (CDGP), a self-limited condition in which puberty starts later than usual but progresses normally. However, some CDGP patients may benefit from medical intervention with low-dose sex steroids or peroral aromatase inhibitor letrozole (only for boys). Other causes of DP include permanent hypogonadotropic hypogonadism, functional hypogonadotropic hypogonadism (due to chronic diseases and conditions), and gonadal failure. In this review we discuss these themes along with the latest achievements in the field of puberty research, and include a brief synopsis on the differential diagnosis and management of patients with CDGP and congenital hypogonadotropic hypogonadism.
Topics: Adolescent; Diagnosis, Differential; Female; Humans; Hypogonadism; Male; Puberty; Puberty, Delayed
PubMed: 31522908
DOI: 10.1016/j.beem.2019.101316 -
Frontiers in Endocrinology 2022The pubertal development onset is controlled by a network of genes that regulate the gonadotropin releasing hormone (GnRH) pulsatile release and the subsequent increase... (Review)
Review
The pubertal development onset is controlled by a network of genes that regulate the gonadotropin releasing hormone (GnRH) pulsatile release and the subsequent increase of the circulating levels of pituitary gonadotropins that activate the gonadal function. Although the transition from pre-pubertal condition to puberty occurs physiologically in a delimited age-range, the inception of pubertal development can be anticipated or delayed due to genetic and epigenetic changes or environmental conditions. Most of the genetic and epigenetic alterations concern genes which encode for kisspeptin, GnRH, LH, FSH and their receptor, which represent crucial factors of the hypothalamic-pituitary-gonadal (HPG) axis. Recent data indicate a central role of the epigenome in the regulation of genes in the hypothalamus and pituitary that could mediate the flexibility of pubertal timing. Identification of epigenetically regulated genes, such as Makorin ring finger 3 () and Delta-like 1 homologue (), respectively responsible for the repression and the activation of pubertal development, provides additional evidence of how epigenetic variations affect pubertal timing. This review aims to investigate genetic, epigenetic, and environmental factors responsible for the regulation of precocious and delayed puberty.
Topics: Humans; Puberty, Precocious; Puberty, Delayed; Gonadotropin-Releasing Hormone; Puberty; Epigenesis, Genetic; Ubiquitin-Protein Ligases
PubMed: 36619551
DOI: 10.3389/fendo.2022.1019468 -
Italian Journal of Pediatrics Mar 2022Constitutional delay of growth and puberty (CDGP) is classified as the most frequent cause of delayed puberty (DP). Finding out the etiology of DP during first... (Review)
Review
BACKGROUND
Constitutional delay of growth and puberty (CDGP) is classified as the most frequent cause of delayed puberty (DP). Finding out the etiology of DP during first evaluation may be a challenge. In details, pediatricians often cannot differentiate CDGP from permanent hypogonadotropic hypogonadism (PHH), with definitive diagnosis of PHH awaiting lack of puberty by age 18 yr. Neverthless, the ability in providing a precise and tempestive diagnosis has important clinical consequences.
MAIN TEXT
A growth failure in adolescents with CDGP may occur until the onset of puberty; after that the growth rate increases with rapidity. Bone age is typically delayed. CDGP is generally a diagnosis of exclusion. Nevertheless, other causes of DP must be evaluated. A family history including timing of puberty in the mother and in the father as well as physical examination may givee information on the cause of DP. Patients with transient delay in hypothalamic-pituitary-gonadal axis maturation due to associated conditions, such as celiac disease, inflammatory bowel diseases, kidney insufficiency and anorexia nervosa, may experience a functional hypogonadotropic hypogonadism. PHH revealing testosterone or estradiol low serum values and reduced FSH and LH levels may be connected to abnormalities in the central nervous system. So, magnetic resonance imaging is required in order to exclude either morphological alterations or neoplasia. If the adolescent with CDGP meets psychological difficulties, treatment is recommended.
CONCLUSION
Even if CDGP is considered a variant of normal growth rather than a disease, short stature and retarded sexual development may led to psychological problems, sometimes associated to a poor academic performance. A prompt and precise diagnosis has an important clinical outcome. Aim of this mini-review is throwing light on management of patients with CDGP, emphasizing the adolescent diagnosis and trying to answer all questions from paediatricians.
Topics: Adolescent; Female; Growth Disorders; Humans; Hypogonadism; Klinefelter Syndrome; Puberty; Puberty, Delayed
PubMed: 35331309
DOI: 10.1186/s13052-022-01242-5 -
The Lancet. Diabetes & Endocrinology Mar 2023Puberty is a major maturational event; its mechanisms and timing are driven by genetic determinants, but also controlled by endogenous and environmental cues.... (Review)
Review
Puberty is a major maturational event; its mechanisms and timing are driven by genetic determinants, but also controlled by endogenous and environmental cues. Substantial progress towards elucidation of the neuroendocrine networks governing puberty has taken place. However, key aspects of the mechanisms responsible for the precise timing of puberty and its alterations have only recently begun to be deciphered, propelled by epidemiological data suggesting that pubertal timing is changing in humans, via mechanisms that are not yet understood. By integrating basic and clinical data, we provide a comprehensive overview of current advances on the physiological basis of puberty, with a particular focus on the roles of kisspeptins and other central transmitters, the underlying molecular and endocrine mechanisms, and the pathways involved in pubertal modulation by nutritional and metabolic cues. Additionally, we have summarised molecular features of precocious and delayed puberty in both sexes, as revealed by clinical and genetic studies. This Review is a synoptic up-to-date view of how puberty is controlled and of the pathogenesis of major pubertal alterations, from both a clinical and translational perspective. We also highlight unsolved challenges that will seemingly concentrate future research efforts in this active domain of endocrinology.
Topics: Male; Female; Humans; Puberty; Kisspeptins; Puberty, Precocious
PubMed: 36620967
DOI: 10.1016/S2213-8587(22)00339-4 -
Endocrine Reviews Sep 2022Delayed puberty (DP) defines a retardation of onset/progression of sexual maturation beyond the expected age from either a lack/delay of the... (Review)
Review
Delayed puberty (DP) defines a retardation of onset/progression of sexual maturation beyond the expected age from either a lack/delay of the hypothalamo-pituitary-gonadal axis activation or a gonadal failure. DP usually gives rise to concern and uncertainty in patients and their families, potentially affecting their immediate psychosocial well-being and also creating longer term psychosexual sequelae. The most frequent form of DP in younger teenagers is self-limiting and may not need any intervention. Conversely, DP from hypogonadism requires prompt and specific treatment that we summarize in this review. Hormone therapy primarily targets genital maturation, development of secondary sexual characteristics, and the achievement of target height in line with genetic potential, but other key standards of care include body composition and bone mass. Finally, pubertal induction should promote psychosexual development and mitigate both short- and long-term impairments comprising low self-esteem, social withdrawal, depression, and psychosexual difficulties. Different therapeutic options for pubertal induction have been described for both males and females, but we lack the necessary larger randomized trials to define the best approaches for both sexes. We provide an in-depth and updated literature review regarding therapeutic options for inducing puberty in males and females, particularly focusing on recent therapeutic refinements that better encompass the heterogeneity of this population, and underlining key differences in therapeutic timing and goals. We also highlight persistent shortcomings in clinical practice, wherein strategies directed at "the child with delayed puberty of uncertain etiology" risk being misapplied to older adolescents likely to have permanent hypogonadism.
Topics: Adolescent; Child; Female; Gonadotropins; Humans; Hypogonadism; Male; Puberty; Puberty, Delayed; Testosterone
PubMed: 34864951
DOI: 10.1210/endrev/bnab043 -
European Journal of Endocrinology Apr 2022An Endo-European Reference Network guideline initiative was launched including 16 clinicians experienced in endocrinology, pediatric and adult and 2 patient...
Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline.
An Endo-European Reference Network guideline initiative was launched including 16 clinicians experienced in endocrinology, pediatric and adult and 2 patient representatives. The guideline was endorsed by the European Society for Pediatric Endocrinology, the European Society for Endocrinology and the European Academy of Andrology. The aim was to create practice guidelines for clinical assessment and puberty induction in individuals with congenital pituitary or gonadal hormone deficiency. A systematic literature search was conducted, and the evidence was graded according to the Grading of Recommendations, Assessment, Development and Evaluation system. If the evidence was insufficient or lacking, then the conclusions were based on expert opinion. The guideline includes recommendations for puberty induction with oestrogen or testosterone. Publications on the induction of puberty with follicle-stimulation hormone and human chorionic gonadotrophin in hypogonadotropic hypogonadism are reviewed. Specific issues in individuals with Klinefelter syndrome or androgen insensitivity syndrome are considered. The expert panel recommends that pubertal induction or sex hormone replacement to sustain puberty should be cared for by a multidisciplinary team. Children with a known condition should be followed from the age of 8 years for girls and 9 years for boys. Puberty induction should be individualised but considered at 11 years in girls and 12 years in boys. Psychological aspects of puberty and fertility issues are especially important to address in individuals with sex development disorders or congenital pituitary deficiencies. The transition of these young adults highlights the importance of a multidisciplinary approach, to discuss both medical issues and social and psychological issues that arise in the context of these chronic conditions.
Topics: Child; Female; Gonadal Steroid Hormones; Hormone Replacement Therapy; Humans; Hypogonadism; Male; Pituitary Diseases; Puberty; Puberty, Delayed; Testosterone; Young Adult
PubMed: 35353710
DOI: 10.1530/EJE-22-0073