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The Journal of Clinical Endocrinology... Jul 2023Central precocious puberty (CPP) classically refers to premature activation of the hypothalamic-pituitary-gonadal axis with onset of sexual development before the age of...
Central precocious puberty (CPP) classically refers to premature activation of the hypothalamic-pituitary-gonadal axis with onset of sexual development before the age of 8 years in girls and 9 years in boys. A decrease in the age of thelarche has been reported over the past several decades; however, the tempo of pubertal progression can be slower and adult height may not be adversely affected in many of the girls who experience thelarche at 6-8 years. Outside of this secular trend in the development itself, the past several decades have also brought about advances in diagnosis and management. This includes the widespread use of an ultrasensitive luteinizing hormone assay, decreasing the need for stimulation testing and a better understanding of the genetics that govern the onset of puberty. Additionally, management of CPP using gonadotropin-releasing hormone analogs (GnRHas) has changed with the advent of new longer-acting formulations. Emerging long-term outcomes of GnRHa administration with regards to obesity, cardiovascular risk factors and fertility are reassuring. Despite these advancements, clinical care in CPP is hampered by the lack of well-designed controlled studies, and management decisions are frequently not supported by clear practice guidelines. Data in boys with CPP are limited and this article focuses on the diagnosis and management of CPP in girls, particularly, in those who present with thelarche at the age of 6-8 years.
Topics: Female; Male; Humans; Child; Gonadotropin-Releasing Hormone; Puberty, Precocious; Sexual Development; Fertility; Heart Disease Risk Factors; Follicle Stimulating Hormone
PubMed: 36916130
DOI: 10.1210/clinem/dgad081 -
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 -
Advances in Endocrinology and Metabolism 1995The past decade has seen tremendous advances in both the diagnosis and treatment options for children with precocious puberty. Although the precise cause of CPP is still... (Review)
Review
The past decade has seen tremendous advances in both the diagnosis and treatment options for children with precocious puberty. Although the precise cause of CPP is still not known, long-acting GnRH analogues provide a safe and effective form of therapy. Treatment slows the progression of secondary sexual characteristics and rates of linear growth and bone maturation. Although the final verdict on how beneficial GnRH analogue therapy is in preserving the final adult height in children with precocious puberty is still not in, achieved heights are generally greater than pretreatment predicted heights. However, treatment may not be appropriate for all children with GDPP. Some children progress through puberty slowly and may not have significant compromise in final height. Furthermore, some children who come from tall families who may be subject to the same deterioration from target height as children who come from short families may not require therapy because their expected final heights may still fall within an acceptable range even if they are shorter than their siblings. Therapy offers the greatest advantage for those children in whom the onset of puberty is at a very early age, those who demonstrate rapidly accelerating bone age, or those with lower genetic height potential. In the past 3 years, the molecular mechanisms by which precocious puberty develops in children with MAS and FMPP have been elucidated. The molecular defects characterized explain the clinical manifestations. Future challenges will include the development of an effective, targeted form of therapy for gonadotropin-independent forms of precocious puberty.
Topics: Child; Female; Glucocorticoids; Gonadotropin-Releasing Hormone; Growth; Humans; Male; Mineralocorticoids; Puberty, Precocious
PubMed: 7671102
DOI: No ID Found -
Best Practice & Research. Clinical... Jun 2019Precocious puberty is defined as the appearance of secondary sex characteristics before 8 years of age in girls and before 9 years of age in boys. Central precocious... (Review)
Review
Precocious puberty is defined as the appearance of secondary sex characteristics before 8 years of age in girls and before 9 years of age in boys. Central precocious puberty (CPP) is diagnosed when activation of the hypothalamic-pituitary axis is identified. It is a rare disease with a clear female predominance. A background of international adoption increases its risk, with other environmental factors such as endocrine disruptors also being associated with CPP. The causes of CPP are heterogeneous, with alterations of the CNS being of special interest. Physical injuries of the CNS are more frequent in boys, while idiopathic etiology is more prevalent among girls. However, in the last decade the number of idiopathic cases has diminished thanks to the discovery of mutations in different genes, including KISS1, KISS1R, MKRN3, and DLK1 that cause CPP. For the diagnosis of CPP, hormone studies are needed in addition to the clinical data regarding signs of pubertal onset. For this purpose, the GnRH test continues to be the gold standard. Imaging analyses, such as bone age and brain MRI, are also very useful. Furthermore, genetic testing must be incorporated in the diagnosis of CPP, especially in familial cases. Early puberty has been related to various consequences in the medium and long term such as behavioral problems, breast cancer, obesity, and metabolic comorbidities. However, there are few studies that have exclusively analyzed patients with CPP. GnRH analogs are the most frequent treatment election with the main objective being to improve adult height. Currently, there are new formulations that are being investigated.
Topics: Child; Female; Gonadotropin-Releasing Hormone; Humans; Male; Neoplasms; Puberty, Precocious
PubMed: 30733078
DOI: 10.1016/j.beem.2019.01.003 -
Advances in Pediatrics Aug 2020
Review
Topics: Body Height; Child; Disease Management; Gonadotropin-Releasing Hormone; Humans; Puberty, Precocious
PubMed: 32591066
DOI: 10.1016/j.yapd.2020.04.003 -
Biomedicine & Pharmacotherapy =... Dec 2022Precocious puberty in children is one of the common endocrine diseases in paediatrics. Epidemiological surveys have shown that the number of children with precocious... (Review)
Review
Precocious puberty in children is one of the common endocrine diseases in paediatrics. Epidemiological surveys have shown that the number of children with precocious puberty has significantly increased globally. Precocious puberty negatively affects the physical and mental health of children and may increase the risk of hypertension, diabetes, obesity and infertility in adulthood. Therefore, the initiating factors of adolescence have become core issues in the study of sexual development in children. Owing to developments in molecular genetics, many studies have been able to show that precocious puberty is mostly resulted in autosomal inheritance. For instance, makorin ring finger protein 3 gene (MKRN3) may be implicated in familial CPP. Gonadotropin-releasing hormone agonist (GnRHa) is the gold standard for treatment, but its safety still requires long-term evaluation and management. Traditional medicinal plants have been used in clinical treatments and in exploring novel treatment methods. From the collected datas, in Asia, traditional Chinese medicine treatment is based on the principles of nourishing Yin, lowering fire and draining fire from the liver to help precocious children and alleviate or delay the onset of precocious puberty by medicinal plants such as Anemarrhena asphodeloides Bge., Phellodendron amurense Rupr., Rehmannia glutinosa and Poria cocos Wolf. They play an important role in exploring the pharmacological mechanisms of precocious puberty treatment effects and drug development. Therefore, by elucidating the occurrence and development of precocious puberty, this review provides novel and valuable insights of paediatric endocrine therapy accessing the published researches on the effectiveness of traditional herbal medicine in the treatment of precocious puberty and its therapeutic mechanisms.
Topics: Child; Humans; Puberty, Precocious; Plants, Medicinal; Gonadotropin-Releasing Hormone; Medicine, Traditional; Ubiquitin-Protein Ligases
PubMed: 36411607
DOI: 10.1016/j.biopha.2022.113907 -
European Journal of Pediatrics Oct 2021The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in... (Review)
Review
The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in boys. It is classified as central precocious puberty when premature maturation of the hypothalamic-pituitary-gonadal axis occurs, and as peripheral precocious puberty when there is excessive secretion of sex hormones, independent of gonadotropin secretion. Precocious sexual maturation is more common in girls, generally central precocious puberty of idiopathic origin. In boys, it tends to be linked to central nervous system abnormalities. Clinical evaluation should include a detailed history and physical examination, including anthropometric measurements, calculation of growth velocity, and evaluation of secondary sexual characteristics. The main sign to suspect the onset of puberty is breast tissue development (thelarche) in girls and testicular enlargement (≥4 mL) in boys. Hormonal assessment and imaging are required for diagnosis and identification of the etiology. Genetic testing should be considered if there is a family history of precocious puberty or other clinical features suggestive of a genetic syndrome. Long-acting gonadotropin-releasing hormone analogs are the standard of care for central precocious puberty management, while peripheral precocious puberty management depends on the etiology.Conclusion: The aim of this review is to address the epidemiology, etiology, clinical assessment, and management of precocious sexual maturation. What is Known: • The main sign to suspect the onset of puberty is breast tissue development (thelarche) in girls and testicular enlargement (≥4 mL) in boys. The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in boys. • Long-acting gonadotropin-releasing hormone agonist (GnRHa) is the standard of care for CPP management, and adequate hormone suppression results in the stabilization of pubertal progression, a decline in growth velocity, and a decrease in bone age advancement. What is New: • Most cases of precocious sexual maturation are gonadotropin-dependent and currently assumed to be idiopathic, but mutations in genes involved in pubertal development have been identified, such as MKRN3 and DLK1. • A different preparation of long-acting GnRHa is now available: 6-month subcutaneous injection.
Topics: Child; Female; Gonadotropin-Releasing Hormone; Humans; Male; Puberty; Puberty, Precocious; Sexual Maturation; Ubiquitin-Protein Ligases
PubMed: 33745030
DOI: 10.1007/s00431-021-04022-1 -
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 -
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 -
Best Practice & Research. Clinical... Jun 2019Peripheral precocious puberty results from peripheral production of sex steroids independent of activation of the hypothalamic-pituitary gonadal axis. It is much less... (Review)
Review
Peripheral precocious puberty results from peripheral production of sex steroids independent of activation of the hypothalamic-pituitary gonadal axis. It is much less common than central precocious puberty. Causes are variable and can be congenital or acquired. In this review, we will discuss the diagnosis and management of the most common etiologies including congenital adrenal hyperplasia, McCune Albright syndrome, familial male-limited precocious puberty, and adrenal and gonadal tumors.
Topics: Adrenal Gland Neoplasms; Adrenal Hyperplasia, Congenital; Female; Fibrous Dysplasia, Polyostotic; Humans; Male; Puberty, Precocious
PubMed: 31027974
DOI: 10.1016/j.beem.2019.04.007