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European Journal of Endocrinology Mar 2024Recent studies suggest that boys enter puberty at a younger age, and the incidence of male central precocious puberty (CPP) is increasing. In this study, we explore the...
OBJECTIVE
Recent studies suggest that boys enter puberty at a younger age, and the incidence of male central precocious puberty (CPP) is increasing. In this study, we explore the incidence of male CPP and identify key clinical and auxological indicators for organic CPP (OCPP).
DESIGN
A retrospective registry-based study.
METHODS
The medical records of 43 boys treated with CPP at the Helsinki University Hospital between 1985 and 2014 were reviewed. Clinical, auxological, and endocrine data of the CPP patients were included in the analyses.
RESULTS
Based on brain MRI, 26% of patients had OCPP. Between 2010 and 2014, the CPP incidence in boys was 0.34 per 10 000 (95% CI 0.20-0.60). Between 1990 and 2014, the male CPP incidence increased (incidence rate ratio [IRR] 1.10, P = .001). This increase was driven by rising idiopathic CPP (ICPP) incidence (IRR 1.11, 95% CI 1.05-1.19, P < .001), while OCPP incidence remained stable (P = .41). Compared with the patients with ICPP, the patients with OCPP were younger (P = .006), were shorter (P = .003), and had higher basal serum testosterone levels (P = .038). Combining 2 to 4 of these readily available clinical cues resulted in good to excellent (all, area under the curve 0.84-0.97, P < .001) overall performance, differentiating organic etiology from idiopathic.
CONCLUSIONS
The estimated incidence of CPP in boys was 0.34 per 10 000, with 26% of cases associated with intracranial pathology. The increase in CPP incidence was driven by rising ICPP rates. Patients with OCPP were characterized by shorter stature, younger age, and higher basal testosterone levels, providing valuable cues for differentiation in addition to brain MRI. Utilizing multiple cues could guide diagnostic decision-making.
Topics: Humans; Male; Luteinizing Hormone; Puberty, Precocious; Follicle Stimulating Hormone; Retrospective Studies; Testosterone; Gonadotropin-Releasing Hormone
PubMed: 38523472
DOI: 10.1093/ejendo/lvae021 -
Expert Review of Endocrinology &... Mar 2019Precocious puberty (PP) is one of the most common reasons for referral to pediatric endocrinologists. Gonadotropin-releasing hormone analogs (GnRHas) are the gold... (Review)
Review
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.
Topics: Gonadotropin-Releasing Hormone; Humans; Puberty, Precocious; Risk Factors; Treatment Outcome
PubMed: 30763521
DOI: 10.1080/17446651.2019.1575726 -
Molecular Genetics & Genomic Medicine Dec 2022Central precocious puberty (CPP) is a precocious puberty due to premature activation of the hypothalamic-pituitary-gonadal axis (HPG). MKRN3 defects are well-known... (Review)
Review
BACKGROUND
Central precocious puberty (CPP) is a precocious puberty due to premature activation of the hypothalamic-pituitary-gonadal axis (HPG). MKRN3 defects are well-known causes of CPP, while DLK1 mutations were recently identified in a few patients with CPP.
METHODS
The study was approved by the Institutional Review and the scientific committee of the hospital. The clinical data were collected. Whole-exome sequencing (WES) was performed to detect causative variants. Key words 'DLK1', 'MKRN3', and "central precocious puberty" were used for literature search in PubMed, Google Scholar, HGMD, and OMIM databases.
RESULTS
The patient, a male, whose puberty began before age nine, had significant metabolic abnormalities including overweight, hyperlipidemia, and hyperuricemia. WES detected a recurrent frame-shift mutation, NM_003836.5:c.479delC(p.P160fs*50) in DLK1 in the patient and his father.
CONCLUSION
The familial DLK1-CPP was identified in China for the first time, which supported that short stature is predicted in patients with CPP without GnRHa treatment. Therefore, we recommend that children with DLK1-CPP should be treated as early as possible to improve adult height. The patient in this study had persistent hyperuricemia, further suggests that this antiadipogenic factor represents a link between reproduction and metabolism.
Topics: Child; Adult; Humans; Male; Puberty, Precocious; Hyperuricemia; East Asian People; Mutation; Puberty; Calcium-Binding Proteins; Membrane Proteins; Ubiquitin-Protein Ligases
PubMed: 36353763
DOI: 10.1002/mgg3.2087 -
Frontiers in Endocrinology 2022As the worldwide secular trends are toward earlier puberty, identification of contributing factors for precocious puberty is critical. We aimed to identify and optimize...
BACKGROUND AND OBJECTIVES
As the worldwide secular trends are toward earlier puberty, identification of contributing factors for precocious puberty is critical. We aimed to identify and optimize contributing factors responsible for onset of precocious puberty machine learning/deep learning algorithms in girls.
METHODS
A cross-sectional study was performed among girls aged 6-16 years from 26 schools in Beijing based on a cluster sampling method. Information was gleaned online questionnaires. Machine/deep learning algorithms were performed using Python language (v3.7.6) on PyCharm platform.
RESULTS
Of 11308 students enrolled, there are 5527 girls, and 408 of them had experienced precocious puberty. Training 13 machine learning algorithms revealed that gradient boosting machine (GBM) performed best in predicting precocious puberty. By comparison, six top factors including maternal age at menarche, paternal body mass index (BMI), waist-to-height ratio, maternal BMI, screen time, and physical activity were sufficient in prediction performance, with accuracy of 0.9530, precision of 0.9818, and area under the receiver operating characteristic curve (AUROC) of 0.7861. The performance of the top six factors was further validated by deep learning sequential model, with accuracy reaching 92.9%.
CONCLUSIONS
We identified six important factors from both parents and girls that can help predict the onset of precocious puberty among Chinese girls.
Topics: China; Cross-Sectional Studies; Deep Learning; Female; Humans; Language; Puberty, Precocious
PubMed: 35846287
DOI: 10.3389/fendo.2022.892005 -
Journal of Clinical Research in... Aug 2022Early puberty is development of secondary sex characteristics earlier than the expected normal age range. We subjectively observed an increased frequency of early...
OBJECTIVE
Early puberty is development of secondary sex characteristics earlier than the expected normal age range. We subjectively observed an increased frequency of early puberty during the Coronavirus disease-2019 (COVID-19) lockdown and aimed to show the clinical, demographic characteristics of the cases and the change in its incidence.
METHODS
Female patients with central precocious puberty (CPP, n=28) and rapidly progressive early puberty (RPEP, n=61), presenting to our clinic before (January 2019-March 2020) and during the COVID-19 pandemic (April 2020-June 2021) were included.
RESULTS
Among 28 CPP cases, six (21%) presented before the pandemic lockdown, whereas 22 (79%) were diagnosed during the COVID-19 pandemic lockdown. While RPEP was seen in 16 (26%) patients before the pandemic, 45 (74%) patients were diagnosed during the lockdown period. Presentation with menarche was seen in 15 RPEP patients; two (13%) were in the prepandemic period and 13 (87%) were in the lockdown period. Chronological age, bone age, bone age to chronological age ratio, height, weight, and body mass index standard deviation scores of patients with RPEP and CPP were similar between the prepandemic and pandemic period.
CONCLUSION
In this cohort, the frequency of CPP and RPP cases were significantly (p<0.001) increased during the COVID-19 pandemic, possibly due to environmental changes.
Topics: COVID-19; Communicable Disease Control; Female; Gonadotropin-Releasing Hormone; Humans; Menarche; Pandemics; Puberty, Precocious
PubMed: 35633642
DOI: 10.4274/jcrpe.galenos.2022.2022-12-11 -
Frontiers in Endocrinology 2023(-)-Epigallocatechin-3-gallate (EGCG) has preventive effects on obesity-related precocious puberty, but its underlying mechanism remains unclear. The aim of this study... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
(-)-Epigallocatechin-3-gallate (EGCG) has preventive effects on obesity-related precocious puberty, but its underlying mechanism remains unclear. The aim of this study was to integrate metabolomics and network pharmacology to reveal the mechanism of EGCG in the prevention of obesity-related precocious puberty.
MATERIALS AND METHODS
A high-performance liquid chromatography-electrospray ionization ion-trap tandem mass spectrometry (LC-ESI-MS/MS) was used to analyze the impact of EGCG on serum metabolomics and associated metabolic pathways in a randomized controlled trial. Twelve weeks of EGCG capsules were given to obese girls in this trail. Additionally, the targets and pathways of EGCG in preventing obesity-related precocious puberty network pharmacology were predicted using network pharmacology. Finally, the mechanism of EGCG prevention of obesity-related precocious puberty was elucidated through integrated metabolomics and network pharmacology.
RESULTS
Serum metabolomics screened 234 endogenous differential metabolites, and network pharmacology identified a total of 153 common targets. These metabolites and targets mainly enrichment pathways involving endocrine-related pathways (estrogen signaling pathway, insulin resistance, and insulin secretion), and signal transduction (PI3K-Akt, MAPK, and Jak-STAT signaling pathways). The integrated metabolomics and network pharmacology indicated that AKT1, EGFR, ESR1, STAT3, IGF1, and MAPK1 may be key targets for EGCG in preventing obesity-related precocious puberty.
CONCLUSION
EGCG may contribute to preventing obesity-related precocious puberty through targets such as AKT1, EGFR, ESR1, STAT3, IGF1, and MAPK1 and multiple signaling pathways, including the estrogen, PI3K-Akt, MAPK, and Jak-STAT pathways. This study provided a theoretical foundation for future research.
Topics: Humans; Female; Network Pharmacology; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Puberty, Precocious; Tandem Mass Spectrometry; Metabolomics; Estrogens; ErbB Receptors
PubMed: 37334310
DOI: 10.3389/fendo.2023.1159657 -
Current Opinion in Pediatrics Aug 2021In this review, we outline the usage and formulations of gonadotropin-releasing hormone analogs (GnRHas) in central precocious puberty (CPP), short stature, and gender... (Review)
Review
PURPOSE OF REVIEW
In this review, we outline the usage and formulations of gonadotropin-releasing hormone analogs (GnRHas) in central precocious puberty (CPP), short stature, and gender diverse individuals, as well as adverse effects, long-term outcomes, and monitoring of therapy. There is a particular focus on citing references published within the last 24 months.
RECENT FINDINGS
Long-acting formulations of GnRHa now include Federal Drug Administration approval for subcutaneous injections. Significant adverse events continue to be rarely reported; extremely rare events include arterial hypertension and pseudotumor cerebri. There continue to be no significant long-term consequences including the impact upon body mass index and bone mineral density, which appear to be transient. GnRHas have been used in differences of sexual development (DSD) and increasingly in the treatment of adolescent transgender individuals.
SUMMARY
GnRHas remain as the only fully efficacious therapy for CPP and effectively suppress pubertal hormones in other situations. The use of GnRHa therapy in gender incongruent individuals has proven beneficial and has become a standard of care, whereas use in those with DSDs should still be considered experimental.
VIDEO ABSTRACT
http://links.lww.com/MOP/A62.
Topics: Adolescent; Body Height; Bone Density; Child; Dwarfism; Gonadotropin-Releasing Hormone; Humans; Puberty, Precocious
PubMed: 34001716
DOI: 10.1097/MOP.0000000000001026 -
Journal of Pediatric Endocrinology &... Dec 2022Use of complementary and alternative medicine (CAM) is widespread. This study aimed to investigate the use of CAM in children with central precocious puberty (PP) who...
OBJECTIVES
Use of complementary and alternative medicine (CAM) is widespread. This study aimed to investigate the use of CAM in children with central precocious puberty (PP) who used gonadotropin-releasing hormone analog (GnRHa) treatment.
METHODS
Parents of 108 patients who were diagnosed as having PP were involved in the study. A questionnaire was administered to the parents during follow-ups. The patients were divided into two groups according to the use of CAM.
RESULTS
Forty (37%) patients had used CAM. Parents who graduated from primary school tended not to use CAM (χ =10.463; p0.015). There was no other statistically significant difference between the sociodemographic features (p0.05) The most common information source was physicians (40%). Seventy-five percentage of CAM users and 44.1% of non-CAM users knew/heard about herbal medicine (χ =8.517 p0.004) and herbal medicine was the most common type of CAM used. 80% of parents in the CAM group and 54.4% of parents in the non-CAM group knew at least one biologically based therapy that had estrogenic activity (χ =6.082 p0.014). Seventy-one percentage of parents in the CAM group and 29% of parents in the non-CAM group stated that they would consider using CAM in the future (χ 16.979 p<0.001).
CONCLUSIONS
The use of CAM among patients with PP is high. Although most CAM therapies are harmless, there may be adverse effects or drug interactions with current conventional treatment in children. Health professionals should be aware and inquire about the use and type of CAM, considering the medical history at every patient encounter.
Topics: Child; Humans; Puberty, Precocious; Complementary Therapies; Surveys and Questionnaires; Parents; Mind-Body Therapies
PubMed: 36288430
DOI: 10.1515/jpem-2022-0305 -
Clinical Obstetrics and Gynecology Sep 2020Onset of puberty, as defined by breast stage 2, appears to be starting at younger ages since the 1940s. There is an ongoing controversy regarding what is normative, as... (Review)
Review
Onset of puberty, as defined by breast stage 2, appears to be starting at younger ages since the 1940s. There is an ongoing controversy regarding what is normative, as well as what is normal, and the evaluation that is deemed necessary for girls maturing before 8 years of age. There are potential implications of earlier pubertal timing, including psychosocial consequences during adolescence, as well as longer term risks, such as breast cancer and cardiometabolic risks. There are additional consequences derived from slower pubertal tempo, for age of menarche has not decreased as much as age of breast development; these include longer interval between sexual initiation and intentional childbearing, as well as a broadened window of susceptibility to endocrine-related cancers.
Topics: Adolescent; Adolescent Development; Body Mass Index; Breast; Breast Neoplasms; Cardiometabolic Risk Factors; Child; Female; Humans; Menarche; Psychology; Puberty; Puberty, Precocious; Sexual Maturation
PubMed: 32482957
DOI: 10.1097/GRF.0000000000000537 -
European Journal of Endocrinology Jul 2015Puberty is a remarkable developmental process with the activation of the hypothalamic-pituitary-gonadal axis culminating in reproductive capacity. It is accompanied by... (Review)
Review
Puberty is a remarkable developmental process with the activation of the hypothalamic-pituitary-gonadal axis culminating in reproductive capacity. It is accompanied by cognitive, psychological, emotional, and sociocultural changes. There is wide variation in the timing of pubertal onset, and this process is affected by genetic and environmental influences. Disrupted puberty (delayed or absent) leading to hypogonadism may be caused by congenital or acquired etiologies and can have significant impact on both physical and psychosocial well-being. While adolescence is a time of growing autonomy and independence, it is also a time of vulnerability and thus, the impact of hypogonadism can have lasting effects. This review highlights the various forms of hypogonadism in adolescence and the clinical challenges in differentiating normal variants of puberty from pathological states. In addition, hormonal treatment, concerns regarding fertility, emotional support, and effective transition to adult care are discussed.
Topics: Adolescent; Female; Humans; Hypogonadism; Male; Puberty, Delayed; Puberty, Precocious
PubMed: 25653257
DOI: 10.1530/EJE-14-0947