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Article ; Online: Central Precocious Puberty - Management and Long-term Outcomes.

Léger, Juliane / Carel, Jean-Claude

European endocrinology

2015 Volume 11, Issue 1, Page(s) 45–46

Abstract: Central precocious puberty (CPP) results from premature re-activation of the gonadotropic axis. CPP ... precocious puberty is more likely to be linked to hypothalamic lesions (≈40%). Recent studies have implicated ... is much more common in girls than in boys and is idiopathic in most cases. In boys ...

Abstract	Central precocious puberty (CPP) results from premature re-activation of the gonadotropic axis. CPP is much more common in girls than in boys and is idiopathic in most cases. In boys, precocious puberty is more likely to be linked to hypothalamic lesions (≈40%). Recent studies have implicated the inactivation of
Language	English
Publishing date	2015-04-11
Publishing country	England
Document type	Editorial
ISSN	1758-3780
ISSN (online)	1758-3780
DOI	10.17925/EE.2015.11.01.45
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Article ; Online: Approach to the Patient: Central Precocious Puberty.

Kilberg, Marissa J / Vogiatzi, Maria G

The Journal of clinical endocrinology and metabolism

2023 Volume 108, Issue 8, Page(s) 2115–2123

Abstract: ... and a better understanding of the genetics that govern the onset of puberty. Additionally, management ... acting formulations. Emerging long-term outcomes of GnRHa administration with regards to obesity ... Central precocious puberty (CPP) classically refers to premature activation of the hypothalamic ...

Abstract	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.
MeSH term(s)	Female ; Male ; Humans ; Child ; Gonadotropin-Releasing Hormone ; Puberty, Precocious/diagnosis ; Puberty, Precocious/etiology ; Puberty, Precocious/therapy ; Sexual Development ; Fertility ; Heart Disease Risk Factors ; Follicle Stimulating Hormone
Chemical Substances	Gonadotropin-Releasing Hormone (33515-09-2) ; Follicle Stimulating Hormone (9002-68-0)
Language	English
Publishing date	2023-03-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgad081
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Article ; Online: Central precocious puberty: a review of diagnosis, treatment, and outcomes.

Zevin, Erika L / Eugster, Erica A

The Lancet. Child & adolescent health

2024 Volume 7, Issue 12, Page(s) 886–896

Abstract: Central precocious puberty (CPP) refers to early activation of the hypothalamic-pituitary-gonadal ... of secondary sexual characteristics to an age that is more commensurate with peers. Although long-term ... management of CPP. Concern for CPP should prompt referral to paediatric endocrinology where diagnosis is ...

Abstract	Central precocious puberty (CPP) refers to early activation of the hypothalamic-pituitary-gonadal (HPG) axis and is manifested by breast development in girls or testicular enlargement in boys before the normal physiological age ranges. CPP can be precipitated by intracranial pathology, exposure to high levels of sex steroids, or environmental risk factors, but most cases are idiopathic. Monogenic causes have also been identified. In this Review, we summarise pathophysiology, risk factors, diagnosis, and management of CPP. Concern for CPP should prompt referral to paediatric endocrinology where diagnosis is confirmed by clinical, biochemical, radiological, and genetic testing. CPP is treated with a gonadotropin-releasing hormone analogue, the primary aims of which are to increase adult height and postpone development of secondary sexual characteristics to an age that is more commensurate with peers. Although long-term outcomes of treatment with gonadotropin-releasing hormone analogues are reassuring, additional research on the psychological effect of CPP is needed.
MeSH term(s)	Adult ; Child ; Female ; Humans ; Male ; Gonadotropin-Releasing Hormone/therapeutic use ; Puberty, Precocious/diagnosis ; Puberty, Precocious/drug therapy
Chemical Substances	Gonadotropin-Releasing Hormone (33515-09-2)
Language	English
Publishing date	2024-03-19
Publishing country	England
Document type	Journal Article ; Review
ISSN	2352-4650
ISSN (online)	2352-4650
DOI	10.1016/S2352-4642(23)00237-7
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Article ; Online: Long-term health consequences of central precocious/early puberty (CPP) and treatment with Gn-RH analogue: a short update.

Soliman, Ashraf T / Alaaraj, Nada / De Sanctis, Vincenzo / Hamed, Noor / Alyafei, Fawzia / Ahmed, Shayma

Acta bio-medica : Atenei Parmensis

2023 Volume 94, Issue 6, Page(s) e2023222

Abstract: Background: The relationship between precocious or early puberty and its treatment has received ... and summarize research articles to elucidate the potential link between precocious or early pubertal ... the risk of coronary heart disease and ischemic strokes and (h) early pubertal timing increases the risk ...

Abstract	Background: The relationship between precocious or early puberty and its treatment has received significant research attention, yielding diverse outcomes. This short review aims to comprehensively analyze and summarize research articles to elucidate the potential link between precocious or early pubertal onset (CPP) and crucial health factors. Methods: We conducted a systematic review of studies published from -January 2000 to March 2023, sourced from databases of Medline, PubMed, Google Scholar and Web of Science. We assessed the relationship between CPP and final adult height (FHt), bone health, reproductive function, body mass index, metabolic and cardiovascular abnormalities, and increased cancer risk. Results: Upon reviewing and analyzing selected studies, the following key findings emerged: (a) treating CPP in girls before age 6-7 and in boys before age 9 improves FHt; (b) bone mineral density (BMD) decreases during GnRHa treatment but normalizes afterward, with no lasting effects on peak bone mass during puberty; (c) GnRH treatment does not negatively affect menstrual cycles; however, untreated CPP increases the risk of premature or early-onset menopause; (d) the incidence of PCOS/hyperandrogenemia may be slightly elevated in women with a history of CPP, but overall reproductive function remains largely unaffected; (e) earlier thelarche and menarche may enhance susceptibility to breast carcinogenesis; (f) CPP contributes to an increased risk of obesity and type 2 diabetes in both genders; (g) early menarche may slightly increase the risk of coronary heart disease and ischemic strokes and (h) early pubertal timing increases the risk of depression and anxiety disorders. Conclusion: Monitoring and early diagnosis of these conditions are of paramount importance for successful management.
MeSH term(s)	Female ; Humans ; Male ; Child ; Diabetes Mellitus, Type 2 ; Gonadotropin-Releasing Hormone ; Puberty, Precocious/drug therapy ; Puberty, Precocious/etiology ; Obesity ; Puberty
Chemical Substances	Gonadotropin-Releasing Hormone (33515-09-2)
Language	English
Publishing date	2023-12-05
Publishing country	Italy
Document type	Systematic Review ; Journal Article
ZDB-ID	2114240-3
ISSN	2531-6745 ; 0392-4203
ISSN (online)	2531-6745
ISSN	0392-4203
DOI	10.23750/abm.v94i6.15316
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Article ; Online: Central precocious puberty: From genetics to treatment.

Aguirre, Rebecca Schneider / Eugster, Erica A

Best practice & research. Clinical endocrinology & metabolism

2018 Volume 32, Issue 4, Page(s) 343–354

Abstract: ... into psychological effects and additional data regarding long-term outcomes, particularly in males, is needed. ... 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 ...

Abstract	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.
MeSH term(s)	Calcium-Binding Proteins ; Child ; Female ; Gonadotropin-Releasing Hormone/analogs & derivatives ; Humans ; Intercellular Signaling Peptides and Proteins/genetics ; Kisspeptins/genetics ; Male ; Membrane Proteins/genetics ; Mutation ; Puberty, Precocious/diagnosis ; Puberty, Precocious/drug therapy ; Puberty, Precocious/genetics ; Ribonucleoproteins/genetics
Chemical Substances	Calcium-Binding Proteins ; DLK1 protein, human ; Intercellular Signaling Peptides and Proteins ; KISS1 protein, human ; Kisspeptins ; Membrane Proteins ; Ribonucleoproteins ; Gonadotropin-Releasing Hormone (33515-09-2) ; MKRN3 protein, human (EC 2.3.2.27)
Language	English
Publishing date	2018-05-26
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2052339-7
ISSN	1878-1594 ; 1532-1908 ; 1521-690X
ISSN (online)	1878-1594 ; 1532-1908
ISSN	1521-690X
DOI	10.1016/j.beem.2018.05.008
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Article ; Online: Update on central precocious puberty: from etiologies to outcomes.

Cantas-Orsdemir, Sena / Eugster, Erica A

Expert review of endocrinology & metabolism

2019 Volume 14, Issue 2, Page(s) 123–130

Abstract: ... in the diagnosis and treatment of CPP remain. While long-term outcomes of patients treated for CPP are encouraging ... of central precocious puberty (CPP) and have an impressive record of safety and efficacy. However, ongoing ... refinements in diagnosis and management continue to lead to important advancements in clinical care.: Areas ...

Abstract	Introduction: Precocious puberty (PP) is one of the most common reasons for referral to pediatric endocrinologists. Gonadotropin-releasing hormone analogs (GnRHas) are the gold standard for the treatment of central precocious puberty (CPP) and have an impressive record of safety and efficacy. However, ongoing refinements in diagnosis and management continue to lead to important advancements in clinical care. Areas covered: The aim of this review is to cover current considerations and controversies regarding the diagnosis of CPP, as well as new findings in regards to etiology and treatment modalities. Expert commentary: There is emerging evidence of monogenic etiologies of CPP and significant progress in the expansion of newer formulations of GnRHas. Despite these exciting developments, areas of uncertainty in the diagnosis and treatment of CPP remain. While long-term outcomes of patients treated for CPP are encouraging, only short-term follow-up is available with respect to the newer extended release GnRHa preparations, and how they compare with historically used formulations is unknown. A particular shortage of information exists pertaining to CPP in boys and regarding the psychological implications of PP in girls, and more research is needed. Continued investigation will yield new insights into the underlying genetics and optimal treatment strategies for CPP.
MeSH term(s)	Gonadotropin-Releasing Hormone/administration & dosage ; Gonadotropin-Releasing Hormone/therapeutic use ; Humans ; Puberty, Precocious/diagnosis ; Puberty, Precocious/etiology ; Risk Factors ; Treatment Outcome
Chemical Substances	Gonadotropin-Releasing Hormone (33515-09-2)
Language	English
Publishing date	2019-02-12
Publishing country	England
Document type	Journal Article ; Review
ISSN	1744-8417
ISSN (online)	1744-8417
DOI	10.1080/17446651.2019.1575726
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Article ; Online: A novel heterozygous MKRN3 nonsense mutation in a Chinese girl with idiopathic central precocious puberty: A case report.

Liu, Meijuan / Fan, Lijun / Gong, Chun Xiu

Medicine

2020 Volume 99, Issue 38, Page(s) e22295

Abstract: ... of weight management and the long-term follow-up to monitor the adverse health outcomes, especially ... with a GnRH analog (3.75 mg every 4 wks) for 1 year and 5 months.: Outcomes: The puberty signs have ... Rationale: Central precocious puberty (CPP) is caused by the premature activation ...

Abstract	Rationale: Central precocious puberty (CPP) is caused by the premature activation of the hypothalamic-pituitary-gonadal axis. Recently, the makorin ring finger protein 3 (MKRN3) mutations represent the most common genetic defects associated with CPP. However, the MKRN3 mutation is relatively rare in Asian countries. Here, we identified a novel heterozygous MKRN3 nonsense mutation (p. Gln363) causing CPP in a Chinese girl. Patient concerns: The index case is a 7-year-old Chinese girl who presented rapidly progressive precocious puberty with the onset of menstrual period 2 months after breast development, the advanced bone age (11 years), and the accelerated growth velocity (10 cm/year). Her basal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, as well as the peak LH/FSH values after the gonadotropin-releasing hormone (GnRH) stimulation test were significantly elevated.Pelvic B ultrasound showed the presence of ovarian follicles with diameters ≥0.4 cm. Uterine length also indicated the onset of puberty. Contrast-enhanced magnetic resonance imaging (MRI) did not disclose any abnormality in the pituitary. Additionally, our present case was obese companies with impaired glucose tolerance (IGT) at the baseline assessment. Genetic analysis revealed a novel heterozygous nonsense mutation (c1087C>T; p. Gln363) in the maternally imprinted MKRN3, which inherited from the girl's father. Diagnosis: Combined with the symptoms, hormonal data, and the results of the pelvic B ultrasound, the girl was diagnosed as CPP. Interventions: The girl has been treated with a GnRH analog (3.75 mg every 4 wks) for 1 year and 5 months. Outcomes: The puberty signs have since not progressed during the follow-up period, which indicates that the GnRH analogs treatment is effective. Lessons: This case was obese companied with IGT at the baseline assessment and exhibited stronger LH/FSH response to GnRH stimulation test. Therefore, clinicians should highlight the importance of weight management and the long-term follow-up to monitor the adverse health outcomes, especially for the polycystic ovary syndrome in later life.
MeSH term(s)	Child ; Female ; Gonadotropin-Releasing Hormone/therapeutic use ; Humans ; Mutation ; Puberty, Precocious/diagnosis ; Puberty, Precocious/drug therapy ; Puberty, Precocious/genetics ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	Gonadotropin-Releasing Hormone (33515-09-2) ; MKRN3 protein, human (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2020-09-21
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000022295
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Article ; Online: MANAGEMENT OF ENDOCRINE DISEASE: Long-term outcomes of the treatment of central precocious puberty.

Guaraldi, Federica / Beccuti, Guglielmo / Gori, Davide / Ghizzoni, Lucia

European journal of endocrinology

2015 Volume 174, Issue 3, Page(s) R79–87

Abstract: ... of outcome. Because randomized controlled trials on the effectiveness and long-term outcomes of treatment are ... and GnRHa itself does not seem to have any long-term effect on BMI. Similarly, analogue treatment does ... GnRH analogues (GnRHa) are the treatment of choice for central precocious puberty (CPP ...

Abstract	GnRH analogues (GnRHa) are the treatment of choice for central precocious puberty (CPP), with the main objective to recover the height potential compromised by the premature fusion of growth cartilages. The aim of this review was to analyze long-term effects of GnRHa on height, body weight, reproductive function, and bone mineral density (BMD) in patients with CPP, as well as the potential predictors of outcome. Because randomized controlled trials on the effectiveness and long-term outcomes of treatment are not available, only qualified conclusions about the efficacy of interventions can be drawn. GnRHa treatment appears to improve adult height in girls with CPP, especially if diagnosed before the age of 6, whereas a real benefit in terms of adult height is still controversial in patients with the onset of puberty between 6 and 8 years of age. No height benefit was shown in patients treated after 8 years. Gonadal function is promptly restored in girls after cessation of treatment, and reproductive potential appears normal in young adulthood. Data are conflicting on the long-term risk of polycystic ovarian syndrome in both treated and untreated women. Fat mass is increased at the start of treatment but normalizes thereafter, and GnRHa itself does not seem to have any long-term effect on BMI. Similarly, analogue treatment does not appear to have a negative impact on BMD. Owing to the paucity of data available, no conclusions can be drawn on the repercussions of CPP and/or its treatment on the timing of menopause and on the health of the offspring.
MeSH term(s)	Body Height ; Body Weight ; Bone Density ; Child ; Child, Preschool ; Delayed-Action Preparations ; Female ; Gonadotropin-Releasing Hormone/analogs & derivatives ; Humans ; Leuprolide/therapeutic use ; Male ; Polycystic Ovary Syndrome/epidemiology ; Puberty, Precocious/drug therapy ; Reproductive Health ; Treatment Outcome ; Triptorelin Pamoate/therapeutic use
Chemical Substances	Delayed-Action Preparations ; Triptorelin Pamoate (08AN7WA2G0) ; Gonadotropin-Releasing Hormone (33515-09-2) ; Leuprolide (EFY6W0M8TG)
Language	English
Publishing date	2015-10-14
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1183856-5
ISSN	1479-683X ; 0804-4643
ISSN (online)	1479-683X
ISSN	0804-4643
DOI	10.1530/EJE-15-0590
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Article: Treatment of central precocious puberty by GnRH analogs: long-term outcome in men.

Bertelloni, Silvano / Mul, Dick

Asian journal of andrology

2008 Volume 10, Issue 4, Page(s) 525–534

Abstract: ... into the range of target height without significant adverse short-term and long-term effects, but longer follow ... In boys, central precocious puberty (CPP) is the appearance of secondary sex characteristics driven ... In the present paper, recent advances of CPP management with GnRH analogs in men are summarized. End results ...

Abstract	In boys, central precocious puberty (CPP) is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the treatment of CPP have been achieved. Because CPP is rare in boys, the majority of papers on this issue focus on girls and do not address specific features of male patients regarding end results and safety. In the present paper, recent advances of CPP management with GnRH analogs in men are summarized. End results in untreated and treated patients are also reviewed by an analysis of the recently published literature on treatment of CPP in men. The available data indicate that therapy with GnRH analogs can improve final height into the range of target height without significant adverse short-term and long-term effects, but longer follow-up of larger series of patients is still required to draw definitive conclusions.
MeSH term(s)	Adolescent ; Adult ; Body Height/drug effects ; Body Height/physiology ; Child ; Dose-Response Relationship, Drug ; Gonadotropin-Releasing Hormone/analogs & derivatives ; Gonadotropin-Releasing Hormone/therapeutic use ; Humans ; Male ; Puberty, Precocious/drug therapy ; Puberty, Precocious/physiopathology ; Sex Characteristics ; Treatment Outcome
Chemical Substances	Gonadotropin-Releasing Hormone (33515-09-2)
Language	English
Publishing date	2008-07
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2075824-8
ISSN	1745-7262 ; 1008-682X
ISSN (online)	1745-7262
ISSN	1008-682X
DOI	10.1111/j.1745-7262.2008.00409.x
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