-
Best Practice & Research. Clinical... Sep 2021Sexual maturation in humans is characterized by a unique individual variability. Pubertal onset is a highly heritable polygenic trait but it is also affected by... (Review)
Review
Sexual maturation in humans is characterized by a unique individual variability. Pubertal onset is a highly heritable polygenic trait but it is also affected by environmental factors such as obesity or endocrine disrupting chemicals. The last 30 years have been marked by a constant secular trend toward earlier age at onset of puberty in girls and boys around the world. More recent data, although more disputed, suggest an increased incidence in idiopathic central precocious puberty. Such trends point to a role for environmental factors in pubertal changes. Animal data suggest that the GnRH-neuronal network is highly sensitive to endocrine disruption during development. This review focuses on the most recent data regarding secular trend in pubertal timing as well as potential new epigenetic mechanisms explaining the developmental and transgenerational effects of endocrine disrupting chemicals on pubertal timing.
Topics: Animals; Endocrine Disruptors; Female; Humans; Male; Obesity; Puberty; Puberty, Precocious; Sexual Maturation
PubMed: 34563408
DOI: 10.1016/j.beem.2021.101579 -
Best Practice & Research. Clinical... Aug 2018Central precocious puberty (CPP) results from early activation of the hypothalamic - pituitary -gonadal (HPG) axis and follows the same sequence as normal puberty. While... (Review)
Review
Central precocious puberty (CPP) results from early activation of the hypothalamic - pituitary -gonadal (HPG) axis and follows the same sequence as normal puberty. While many factors involved in pubertal initiation remain poorly understood, the kisspeptin system is known to play a key role. Currently, mutations in the kisspeptin system, MKRN3, and DLK1 have been identified in sporadic and familial cases of CPP. The diagnosis is based on physical exam findings indicating advancing puberty and on laboratory tests confirming central HPG axis activation. GnRH analogs are the mainstay of treatment and are used with the goal of height preservation. Newer extended release formulations continue to be developed. Currently there is no evidence of long-term complications associated with treatment. However, many areas remain to be explored such as targeted therapies and aspects of clinical management. Further investigation into psychological effects and additional data regarding long-term outcomes, particularly in males, is needed.
Topics: Calcium-Binding Proteins; Child; Female; Gonadotropin-Releasing Hormone; Humans; Intercellular Signaling Peptides and Proteins; Kisspeptins; Male; Membrane Proteins; Mutation; Puberty, Precocious; Ribonucleoproteins; Ubiquitin-Protein Ligases
PubMed: 30086862
DOI: 10.1016/j.beem.2018.05.008 -
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 -
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 -
Acta Bio-medica : Atenei Parmensis Sep 2019Central precocious puberty (CPP) is defined as an early pubertal development that occurs before the age of 9 years in boys and 8 years in girls. It results from... (Review)
Review
Long-term effects and significant Adverse Drug Reactions (ADRs) associated with the use of Gonadotropin-Releasing Hormone analogs (GnRHa) for central precocious puberty: a brief review of literature.
Central precocious puberty (CPP) is defined as an early pubertal development that occurs before the age of 9 years in boys and 8 years in girls. It results from premature activation of the hypothalamic-pituitary-gonadal axis. Gonadotropin-releasing hormone agonists (GnRHa) have been the gold standard therapy for CPP for more than 30 years. These compounds have a high affinity for the pituitary LHRH receptor and are resistant to enzymatic degradation. Through continuous stimulation, GnRHa inhibit the pulsatile secretion of gonadotropin, resulting in hormonal suppression, cessation of pubertal development, and normalization of growth and skeletal maturation rates. The goal of therapy is to halt pubertal progression and delay epiphyseal maturation that leads to improvement of final adult height. There are no widely accepted guidelines for how long to continue treatment with a GnRHa for CPP, and individual practice varies widely. Furthermore, conflicting results have been published on the long-term effects of GnRHa therapy in patients with CPP. Therefore, we reviewed the current literature focusing our attention on the long-term effects and the significant adverse drug reactions (ADRs) observed during treatment with GnRHa in patients with CPP. Our review may provide the necessary data to enable clinicians to administer GnRHa in the safest and most appropriate way. Further studies are necessary to identify the mechanisms of development of potential adverse drug reactions related to GnRHa therapy in CPP.
Topics: Body Height; Body Weight; Bone Density; Drug-Related Side Effects and Adverse Reactions; Female; Gonadotropin-Releasing Hormone; Humans; Polycystic Ovary Syndrome; Puberty, Precocious
PubMed: 31580327
DOI: 10.23750/abm.v90i3.8736 -
Pediatrics Apr 2009Gonadotropin-releasing hormone analogs revolutionized the treatment of central precocious puberty. However, questions remain regarding their optimal use in central... (Review)
Review
OBJECTIVE
Gonadotropin-releasing hormone analogs revolutionized the treatment of central precocious puberty. However, questions remain regarding their optimal use in central precocious puberty and other conditions. The Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology convened a consensus conference to review the clinical use of gonadotropin-releasing hormone analogs in children and adolescents.
PARTICIPANTS
When selecting the 30 participants, consideration was given to equal representation from North America (United States and Canada) and Europe, an equal male/female ratio, and a balanced spectrum of professional seniority and expertise.
EVIDENCE
Preference was given to articles written in English with long-term outcome data. The US Public Health grading system was used to grade evidence and rate the strength of conclusions. When evidence was insufficient, conclusions were based on expert opinion.
CONSENSUS PROCESS
Participants were put into working groups with assigned topics and specific questions. Written materials were prepared and distributed before the conference, revised on the basis of input during the meeting, and presented to the full assembly for final review. If consensus could not be reached, conclusions were based on majority vote. All participants approved the final statement.
CONCLUSIONS
The efficacy of gonadotropin-releasing hormone analogs in increasing adult height is undisputed only in early-onset (girls <6 years old) central precocious puberty. Other key areas, such as the psychosocial effects of central precocious puberty and their alteration by gonadotropin-releasing hormone analogs, need additional study. Few controlled prospective studies have been performed with gonadotropin-releasing hormone analogs in children, and many conclusions rely in part on collective expert opinion. The conference did not endorse commonly voiced concerns regarding the use of gonadotropin-releasing hormone analogs, such as promotion of weight gain or long-term diminution of bone mineral density. Use of gonadotropin-releasing hormone analogs for conditions other than central precocious puberty requires additional investigation and cannot be suggested routinely.
Topics: Adolescent; Body Height; Bone Density; Child; Female; Gonadotropin-Releasing Hormone; Humans; Hypothyroidism; Luteinizing Hormone; Nafarelin; Organ Size; Ovary; Polycystic Ovary Syndrome; Puberty, Precocious; Uterus
PubMed: 19332438
DOI: 10.1542/peds.2008-1783 -
BMC Pediatrics Nov 2021Obesity is an important underlying cause of central precocious puberty (CPP), but previous large studies are flawed by using just age and breast examination to diagnose...
BACKGROUND
Obesity is an important underlying cause of central precocious puberty (CPP), but previous large studies are flawed by using just age and breast examination to diagnose CPP. We aimed to determine whether overweight and obesity in childhood increases hormonally diagnosed CPP.
METHODS
Our retrospective, case-control study recruited 846 children diagnosed as having CPP and randomly sampled 1650 healthy control subjects in Xingtai Third Hospital in China between November 2018 and March 2021. Information was obtained from an electronic medical record and questionnaire investigated in the outpatient visit. Observations were made before the a priori hypothesis. Unconditional logistic regression for analysis was used to determine whether overweight and obesity status and duration of overweight/obesity were associated with CPP.
RESULTS
Overweight and obesity were significantly associated with increased odds of CPP among girls, even after adjusting for birth weight, exclusive breastfeeding for 6 month, household income, maternal overweight, paternal overweight, and maternal menarche age (overweight: the adjusted odds ratio (aOR) (95%CI): 1.92 (1.16, 3.24), p = 0.02; obesity: aOR (95%CI): 1.78 (1.13, 3.48), p = 0.03). Furthermore, the effects of overweight and obesity were significant when ongoing for 1 to 2 years, 2 to 3 years, and greater than 3 years, but not at less than 1 year. For boys, association between obesity and increased odds of CPP was observed (aOR (95%CI): 1.68 (1.09, 3.75), p = 0.03). The effects of overweight and/or obesity were only significant when ongoing for greater than 2 years.
CONCLUSIONS
Prolonged overweight and obesity in early childhood may be risk factors for CPP, especially in girls. Weight loss might be an important approach for the prevention of precocious puberty in children.
Topics: Case-Control Studies; Child; Child, Preschool; Female; Humans; Male; Pediatric Obesity; Puberty, Precocious; Retrospective Studies; Risk Factors
PubMed: 34784914
DOI: 10.1186/s12887-021-02936-1 -
International Journal of Molecular... May 2023McCune-Albright syndrome (MAS) is a rare sporadic condition defined by the classic triad of fibrous dysplasia of bone, café au lait skin macules, and hyperfunctioning... (Review)
Review
McCune-Albright syndrome (MAS) is a rare sporadic condition defined by the classic triad of fibrous dysplasia of bone, café au lait skin macules, and hyperfunctioning endocrinopathies. The molecular basis of MAS has been ascribed to the post-zygotic somatic gain-of-function mutations in the gene, which encodes the alpha subunit of G proteins, leading to constitutive activation of several G Protein-Coupled Receptors (GPCRs). The co-occurrence of two of the above-mentioned cardinal clinical manifestations sets the diagnosis at the clinical level. In this case report, we describe a 27-month-old girl who presented with gonadotropin-independent precocious puberty secondary to an estrogen-secreting ovarian cyst, a café au lait skin macule and growth hormone, and prolactin excess, and we provide an updated review of the scientific literature on the clinical features, diagnostic work-up, and therapeutic management of MAS.
Topics: Female; Humans; Child, Preschool; Fibrous Dysplasia, Polyostotic; Puberty, Precocious; Endocrine System Diseases; Human Growth Hormone; Cafe-au-Lait Spots
PubMed: 37239810
DOI: 10.3390/ijms24108464 -
Archivos Argentinos de Pediatria Jun 2023
Topics: Humans; Puberty, Precocious; COVID-19; Argentina
PubMed: 36893338
DOI: 10.5546/aap.2023-03028.eng -
Endocrinology and Metabolism Clinics of... Dec 2020Delayed puberty may signify a common variation of normal development, or indicate the presence of a pathologic process. Constitutional delay of growth and puberty is a... (Review)
Review
Delayed puberty may signify a common variation of normal development, or indicate the presence of a pathologic process. Constitutional delay of growth and puberty is a strongly familial type of developmental pattern and accounts for the vast majority of children who are "late bloomers." Individuals with sex chromosomal abnormalities frequently have hypergonadotropic hypogonadism. There are currently 4 known monogenic causes of central precocious puberty. The primary treatment goal in children with hypogonadism is to mimic normal pubertal progression, while the primary aims for the management of precocious puberty are preservation of height potential and prevention of further pubertal development.
Topics: Adolescent; Child; Humans; Hypogonadism; Puberty, Delayed; Puberty, Precocious
PubMed: 33153677
DOI: 10.1016/j.ecl.2020.08.002