Short Adult Height After Rapid-tempo Puberty: When is it too Late to Treat?

A rarely reported phenomenon of rapid-tempo puberty in which the physical changes of puberty and testosterone levels increase very rapidly has not been reported outside apart from in two reviews. The resulting rapid advancement of skeletal age causes early completion of growth with shorter adult stature than expected. This appears to be genetic given its occurrence in the present report in two families, one with three brothers, one with two. We also describe potential treatments and found for the youngest that early initiation of standard therapy preserved or reclaimed adult height (AH) potential. The foreshortened AH in this situation involves rapidly advancing puberty resulting from high circulating testosterone levels leading to rapid advance in skeletal age. This was recognized earlier among younger brothers and treatment with gonadotropin-releasing analogues, growth hormone (GH) and/or aromatase inhibitor therapy (AIT) was tried. Two brothers in family A and family B were treated. Case 5 started treatment early enough so his AH was within target height (mid-parental height) range. Cases 2, 3, 4 were tried on GH and/or AIT with outcomes suggesting benefit. The prevalence and mechanism of rapid-tempo puberty requires further study. Furthermore, as illustrated by two of the current cases, this phenomenon may have a heightened prevalence, or at least may occur, in children previously diagnosed with constitutional delay of growth, underscoring the need to be cautious in assurance of a normal AH outcomes in this population, based on data from a single assessment.

A pediatric case of two Nicolau syndrome lesions following leuprolide injection in the upper extremity.

ABSTRACT: Nicolau syndrome (NS) is a rare and unpredictable adverse reaction that can occur after the administration of certain medications. A 9-year-old girl, accompanied by her father, visited the outpatient dermatology clinic with complaints of wounds on both upper arms. Upon reviewing her medical history, it was discovered that she had been receiving leuprolide for precocious puberty, and the symptoms began after the last two injections. The patient experienced pain during the leuprolide injection, and redness and swelling were noticed in the injection area on the same day. A few days later, the redness turned into ulcers. The fact that the development of NS cannot be detected in advance and the risk of rapid progression of tissue necrosis make disease management difficult. The prognosis of NS significantly depends on the patient, and when a developing lesion is noticed early, it is crucial to minimize the risk of complications.

Effectiveness of leuprolide acetate administered monthly compared to three-monthly in the treatment of central precocious puberty: evaluation at the end of treatment.

Introduction: Gonadotropin-releasing hormone (GnRH) analogs are the standard treatment for central precocious puberty (CPP). Although there are numerous varieties of GnRH agonists, the effectiveness of 1-monthly compared with 3-monthly Leuprolide acetate is still restricted. The objective of this study was to evaluate the outcomes of CPP treatment with Leuprolide acetate at a 1-monthly dosage of 3.75 mg, in comparison to a dosage of 11.25 mg administered every 3 months. Method: This retrospective cohort study involved 143 girls diagnosed with CPP with 72 of them receiving the monthly treatment regimen and 71 receiving the 3-monthly treatment regimen. Anthropometric measurements were compared at the start and end of the therapy. The rates and level of LH suppression were assessed six months after therapy. Results: The regimen administered every 3 months showed more significant suppression of LH. The 3-monthly group showed lower actual height and degree of bone age advancement at the end of therapy. However, the predicted adult height (PAH) remained comparable in both groups. Conclusion: The 3-monthly treatment showed greater hormonal and growth suppression effects, but there was no significant difference in PAH between the two groups.

Anastrozole monotherapy further improves near-adult height after the initial combined treatment with leuprorelin and anastrozole in early-maturing girls with compromised growth prediction: results from the second phase of the GAIL study.

Background: The first phase of the GAIL study ("Girls treated with an Aromatase Inhibitor and Leuprorelin," ISRCTN11469487) has shown that the combination of anastrozole and leuprorelin for 24 months is safe and effective in improving the predicted adult height (PAH) in girls with early puberty and compromised growth prediction by +1.21 standard deviation score (SDS; +7.51 cm) compared to inhibition of puberty alone, +0.31 SDS (+1.92 cm). Objectives and hypotheses: In the second phase of the GAIL study, we assessed the adult height (AH)/near-adult height (NAH) at the end of the first phase and, in addition, the efficacy of anastrozole monotherapy thereafter in further improving NAH. Methods: We measured the AH (age 16.5 years)/NAH [bone age (BA), 15 years] of the 40 girls included, divided into two matched groups: group A (20 girls on anastrozole + leuprorelin) and group B (20 girls on leuprorelin alone). Group A was further randomized into two subgroups: A1 and A2. Group A1 (n = 10), after completion of the combined therapy, received anastrozole 1 mg/day as monotherapy until BA 14 years, with a 6-month follow-up. Group A2 (n = 10) and group B (n = 20), who received only the combined treatment and leuprorelin alone, respectively, were recalled for evaluation of AH/NAH. Results: AH or NAH exceeded the PAH at the completion of the 2-year initial phase of the GAIL study in all groups, but the results were statistically significant only in group A1: NAH-PAH group A1, +3.85 cm (+0.62 SDS, p = 0.01); group A2, +1.6 cm (+0.26 SDS, p = 0.26); and group B, +1.7 cm (+0.3 SDS, p = 0.08). The gain in group A1 was significantly greater than that in group A2 (p = 0.04) and in group B (p = 0.03). Anastrozole was determined to be safe even as monotherapy in Group A1. Conclusions: In early-maturing girls with compromised growth potential, the combined treatment with leuprorelin and anastrozole for 2 years or until the age of 11 years resulted in a total gain in height of +9.7 cm when continuing anastrozole monotherapy until the attainment of NAH, as opposed to +7.4 cm if they do not continue with the anastrozole monotherapy and +3.6 cm when treated with leuprorelin alone. Thus, the combined intervention ends at the shortest distance from the target height if continued with anastrozole monotherapy until BA 14 years.

Timing of onset of menses after GnRH agonist treatment for central precocious puberty.

OBJECTIVES: To understand possible predictors of the onset of menses after gonadotropin-releasing hormone agonist treatment cessation in girls with central precocious puberty (CPP). METHODS: This exploratory post hoc analysis of a phase 3 and 4 trial of girls with CPP treated with once-monthly intramuscular leuprolide acetate examined onset of menses after treatment completion using a time-to-event analysis. Pretreatment and end-of-treatment chronologic age (CA), bone age (BA)/CA ratio, and Tanner breast stage; pretreatment menses status; and end-of-treatment BA and body mass index (BMI) were studied as potential factors influencing the onset of menses. RESULTS: Median time to first menses after stopping treatment was 18.3 months among 35 girls (mean age at onset of treatment, 6.8 years) examined. Of 26 girls experiencing menses, 11 (42 %) menstruated at 16-21 months after stopping treatment. Most girls with pretreatment BA/CA≥1.4 started menstruating very close to 18 months after stopping treatment; those with less advanced BA/CA experienced menses at 9-18 months. End-of-treatment BA/CA≥1.2 was associated with a quicker onset of menses (14.5 vs. 18.5 months for BA/CA<1.2, p=0.006). End-of-treatment BA≥12 years predicted longer time to menses. No relationship with time to menses was observed for pretreatment menarche status, pretreatment or end-of-treatment Tanner breast stage (<3/≥3) or CA (<6/≥6 or ≤11/>11), or end-of-treatment BMI percentiles (<85.6/≥85.6 and <92.6/≥92.6). CONCLUSIONS: Pretreatment menarche status or CA do not appear to predict onset of menses, but pre- and end-of-treatment BA/CA may be helpful in anticipating time to first menses after stopping treatment.

Diagnosis, Treatment, and Outcomes of Males with Central Precocious Puberty.

Central precocious puberty (CPP) among males is less frequent than among females but more likely to have an underlying pathologic cause. Diagnosis of CPP is often straightforward among males because increased testicular volume, the first sign of puberty, can be verified although careful central nervous system (CNS) assessment is generally necessary. Treatment with gonadotropin-releasing hormone agonist (GnRHa) is indicated, given in conjunction with any therapy needed for CNS lesions. Monitoring of treatment usually can consist of evaluating growth and physical puberty and with testosterone levels as the only lab data. Short-term and long-term outcome data indicate efficacy and safety, although data are limited. Such data need to be reported.

Congenital adrenal hyperplasia complicated by gonadotropin-dependent precocious puberty.

Precocious puberty, characterised by the early appearance of secondary sexual characteristics, poses challenges in diagnosis and management. Here, we describe a case of precocious puberty diagnosed in a boy in middle childhood, who presented with progressive phallus enlargement, pubic hair development and increased aggressive behaviour. Hormonal evaluation confirmed the diagnosis of congenital adrenal hyperplasia (CAH), complicated by gonadotropin-dependent precocious puberty. The case highlights the importance of assessment of testicular volume in a patient presenting with precocious puberty. Symmetrical testicular enlargement in a patient with CAH suggests premature activation of the hypothalamic-pituitary-gonadal axis. The patient received glucocorticoid therapy to suppress androgen production related to CAH and gonadotropin-releasing hormone analogue therapy to control premature activation of the hypothalamic-pituitary-gonadal axis. Follow-up visits showed regression of secondary sexual characteristics and improved growth velocity.

Network pharmacology combined with lipidomics to reveal the regulatory effects and mechanisms of Kangzao granules in the hypothalamus of rats with central precocious puberty.

Central precocious puberty (CPP) is a prevalent endocrine disorder that primarily affects children, specifically females, and is associated with various physical and psychological complications. Although Kangzao granules (KZG) are efficacious in managing CPP, the underlying mechanisms remain unclear. Therefore, this study aimed to elucidate the therapeutic mechanisms of KZG using network pharmacology, molecular docking, pharmacodynamics, and pathway validation. A putative compound-target-pathway network was constructed using Cytoscape, before KEGG and Gene Ontology enrichment analyses were conducted. Moreover, molecular docking was performed using AutoDockTools. Quality control of the 10 key components of KZG was carried out using UHPLC-ESI/LTQ-Orbitrap-MS/MS, and hypothalamic lipids were analyzed using UHPLC-Q-Exactive Orbitrap MS/MS. In total, 87 bioactive compounds that targeting 110 core proteins to alleviate CPP were identified in KZG. Lipidomic analysis revealed 18 differential lipids among the CPP, KZG, and control groups, wherein fatty acids were significantly reduced in the model group; however, these changes were effectively counteracted by KZG treatment. Molecular docking analysis revealed a strong binding affinity between flavonoids and RAC-alpha serine/threonine-protein kinase (AKT) when docked into the crystal structure. Moreover, a substantial disruption in lipid metabolism was observed in the model group; however, treatment with KZG efficiently reversed these alterations. Furthermore, the phosphoinositide 3-kinase/AKT signaling pathway was identified as a pivotal regulator of hypothalamic lipid metabolism regulator. Overall, this study highlights the effectiveness of a multidisciplinary approach that combines network pharmacology, lipidomics, molecular docking, and experimental validation in the elucidation of the therapeutic mechanisms of KZG in CPP treatment.

The effect of GnRH analog treatment on BMI in children treated for precocious puberty: a systematic review and meta-analysis.

INTRODUCTION: The purpose of the present meta-analysis was to systematically evaluate the effect of GnRHa treatment on the BMI of children with precocious puberty after GnRHa treatment as compared to before, and to analyze the effect of GnRHa treatment on the body composition of children with precocious puberty at different BMIs by classifying into normal body mass, overweight, and obese groups according to BMI at the time of initial diagnosis. CONTENT: A meta-analysis was performed using Stata 12.0 software by searching PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), and Wan fang database for relevant literature on standard deviation score of body mass index (BMI-SDS) after GnRHa treatment as compared to before in children with precocious puberty. SUMMARY: A total of eight studies were included with a total sample size of 715 cases, and the results of meta-analysis showed that BMI-SDS increased in children with precocious puberty after GnRHa treatment as compared to before starting [(weighted mean difference (WMD)=0.23, 95 % CI: 0.14-0.33, p=0.000)] and also increased in children with normal body mass [(WMD=0.37, 95 % CI: 0.28-0.46, p=0.000)], and there was no significant change in BMI-SDS in children in the overweight or obese group [(WMD=0.01, 95 % CI: -0.08-0.10, p=0.775)]. OUTLOOK: Overall, there was an observed increase in BMI-SDS at the conclusion of GnRHa treatment in children with precocious puberty. Additionally, it was found that the effect of GnRHa treatment on body composition varied among children with different BMI status. Clinicians should emphasize the promotion of a healthy lifestyle and personalized dietary management for children.

The effect of gonadoliberin analog treatment in precocious puberty on polycystic ovarian syndrome prevalence in adulthood.

Precocious puberty is diagnosed when pubertal characteristics appear before the age of 8 years in females. The most common form is gonadotropin-dependent, called axial. The primary method of treatment is administration of gonadotrophin-releasing hormone analogues (GnRHa). The aim of the study was to verify hypothesis that GnRHa therapy in the childhood may be of additive risk factor for polycystic ovary syndrome (PCOS) in adulthood. Material and Methods: The study group consists of 24 women (median age 22 88 years, median BMI 23.5) treated with GnRHa for central precocious puberty in childhood. The control group includes 40 women (median age 23 years, median BMI 25.6) diagnosed with isolated premature thelarche and not using GnRHa in the childhood. Anthropometric measurements, ultrasound examination of minor pelvis and hormonal profile were performed. PCOS diagnosis was based on Rotterdam criteria. Results: The study confirmed a higher prevalence of PCOS in the study group (50%) than in the control group (10%); p=0.0006. Significant, linear correlation between free testosterone levels and ovarian size was found in the study group (R=0.45 p= 0.03). Conclusions: GnRHa therapy during childhood may have a potential influence on incidence of PCOS in the adulthood. Therefore, in this group of patients long-term follow-up focused on screening for PCOS would seem beneficial.

The effect of gonadotropin-releasing hormone analog treatment on the endocrine system in central precocious puberty patients: a meta-analysis.

OBJECTIVES: Gonadotropin-releasing hormone (GnRHa) is the first choice for the treatment of patients with central precocious puberty (CPP). However, the effects of GnRHa on the endocrine system of CPP patients, including insulin sensitivity, lipid level, thyroid function, bone mineral density (BMD), and testosterone (T) level, are currently contradictory. Therefore, the long-term safety of GnRHa therapy remains controversial. CONTENT: A systematic literature search was performed using PubMed, Embase, Cochrane Library, and CNKI databases. The changes in HOMA-IR, TG, LDL-C, HDL-C, TSH, FT3, FT4, T, and BMD in CPP patients before and after GnRHa treatment were compared by meta-analysis. As the heterogeneity between studies, we estimated standard deviation mean differences (SMDs) and 95 % confidence intervals (CIs) using a random-effects model. Egger's test was used to assess publication bias. SUMMARY: A total of 22 studies were included in our meta-analysis. Compared with before GnRHa treatment, there were no statistically significant differences in endocrine indicators including HOMA-IR, TG, LDL-C, HDL-C, TSH, FT4, FT3, T, and BMD of CPP patients treated with GnRHa. OUTLOOK: Treatment with GnRHa for central precocious puberty will not increase the adverse effect on the endocrine system.

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With the changes in various factors such as genetics and the environment, the incidence of childhood precocious puberty has been gradually increasing. Improving height is one of the key issues in the clinical management of precocious puberty. Currently, gonadotropin-releasing hormone analogs (GnRHa) remain the preferred treatment for precocious puberty, but their effect on height improvement is influenced by multiple factors, which may result in lower-than-expected height benefits. Combining recombinant human growth hormone (rhGH) therapy with GnRHa treatment is an alternative strategy to enhance the efficacy of GnRHa, but there is still no clear recommendation regarding the timing of their combination. Considering the current status of precocious puberty treatment, it is crucial to reevaluate the effects of GnRHa monotherapy and combination therapy with rhGH on height improvement. This article discusses strategies such as combination therapy indications to guide clinical medication and help children with precocious puberty achieve optimal height benefits.

Efficacy and safety of leuprorelin 3-month depot (11.25 mg) for idiopathic central precocious puberty treatment of Chinese girls: a single-center retrospective study.

OBJECTIVES: This study aimed to evaluate the efficacy and safety of 3-month leuprorelin acetate (3-month LA, 11.25 mg) for the treatment of idiopathic central precocious puberty (ICPP) in Chinese girls. METHODS: We conducted a single-center retrospective study in China on 28 girls with ICPP who received at least one year of 3-month LA treatment. Data from anthropometry, biochemistry, bone age (BA), and pelvic ultrasonography were assessed before and every 6 months during medication. RESULTS: At CPP diagnosis, the mean chronological age (CA) was 7.8±0.8 years, with bone age advancement (BA-CA) of 1.5±0.8 years. After treatment initiation, growth velocity decreased significantly from 8.5±1.6 cm/year to 5.8±1.1 cm/year at month 12 (p<0.001). GnRH-stimulated peak LH ≤3IU/L, the primary efficacy criterion, was observed in 27 out of 28 (96.4 %) children at month 3. Basal estradiol <20 pg/mL was achieved by all 28 girls (100 %) at month 6 and remained stable at month 12. Basal follicle-stimulating hormone (FSH) decreased from 4.1±3.5 to 1.7±0.9 (p<0.001), and basal LH was also significantly reduced from 3.3±6.5 to 0.7±0.8 (p=0.035) at month 12. The mean predicted adult height (PAH) at treatment initiation was 152.7±5.8 cm, it increased significantly to 157.5±5.5 cm (p=0.007) after one-year treatment. Pubertal development was slowed in most patients, and in some cases, it was even reversed. Only one patient (3.6 %) reported local intolerance. CONCLUSIONS: Three-month leuprorelin acetate is a safe and effective treatment for suppressing the pituitary-gonadal axis and restoring impaired adult height in Chinese girls.

Prevalence of Polycystic Ovarian Syndrome in Girls with a History of Idiopathic Central Precocious Puberty.

INTRODUCTION: The prevalence of polycystic ovarian syndrome (PCOS) in adolescent girls is between 1 and 4.3%. It remains controversial whether women with a history of idiopathic central precocious puberty (ICPP) are at increased risk for PCOS. Our objective was to assess the prevalence of PCOS in adolescents with a history of ICPP compared with healthy adolescents and the prevalence of PCOS among ICPP girls who have received or not gonadotropin-releasing hormone analogue (GnRHa) treatment. METHODS: We assessed post-menarcheal girls with a history of ICPP. Girls were evaluated at gynecological age ≥2.5 years. Data collected were age at menarche, menstrual cycle characteristics, BMI, clinical hyperandrogenism (HA), total and free testosterone levels. PCOS diagnosis was defined by criteria for adolescents. Subjects were also analyzed regarding whether or not they had received GnRHa treatment. RESULTS: Ninety-four subjects were assessed, and 63 had been treated with GnRHa. Menstrual disorders were found in 29%, clinical HA in 36%, and biochemical HA in 23%. Twelve percent met the diagnostic criteria for PCOS. There was no difference in BMI or in the incidence of menstrual dysfunction or hyperandrogenemia between treated and untreated patients. A higher proportion of clinical HA was found in untreated patients when compared to treated girls. The relative risk (RR) of developing PCOS in ICPP girls was 2.5 compared to a population of healthy adolescents. This RR was not higher in patients who received treatment with GnRHa than in those who did not. CONCLUSION: Adolescent girls with a history of ICPP have an increased risk of PCOS. This risk seems not to be related to GnRHa treatment.

Longitudinal assessment of auxological parameters, adult height outcome and its determinants in leuprolide-treated Indian girls with idiopathic central precocious puberty.

OBJECTIVES: To assess auxological parameters, adult height outcome and its determinants in Indian girls with idiopathic central precocious puberty (iCPP) treated with gonadotropin-releasing hormone analogues (GnRHa). METHODS: Retrospective study. Inclusion: data on girls with iCPP from initiation to stopping GnRHa (n=179). Exclusion: boys, peripheral, organic central precocity. RESULTS: Mean age of starting GnRHa: 8.2± 1.1 years, duration: 2.8± 1.2 years. 11.7 % had attained menarche at first presentation. The difference between bone (BA) and chronological (CA) ages reduced significantly from 2.6± 0.9 years (onset) to 1.6± 0.8 years (cessation). Weight, BMI Z-scores increased (p<0.01), height Z-scores decreased (0.8 vs. 0.6; p<0.01), predicted adult height (PAH) and Z-scores improved by 3.5 cm, 0.5 SDS following treatment (p<0.01). Overweight/obese girls (vs. normal BMI) were taller, with more advanced BA at starting (height Z-score: 0.7 vs. 1.0, BA-CA: 2.2 vs. 2.9 years), stopping (height Z-score: 0.5 vs. 0.9, BA-CA: 1.4 vs. 1.9 years) treatment, but showed no difference in PAH at starting, stopping treatment. Adult height data (n=58) revealed 1.9 cm gain above target height. Adult height Z-scores significantly exceeded target height Z-scores (p<0.01). Mean adult height (157.1± 5.8 cm) crossed PAH at starting treatment (155.9± 6.4 cm) but remained 1.6 cm lesser than PAH at cessation. Adult weight, BMI Z-scores (-0.2± 1.3, -0.1± 1.2) were significantly lower (p<0.01) than those at stopping GnRHa. Height gain adjusted for age at starting GnRHa correlated negatively with height, weight, BMI, Tanner-staging, BA, FSH, Estradiol at treatment onset, BA at cessation, and correlated positively with treatment duration. CONCLUSIONS: GnRHa treatment in Indian girls with iCPP resulted in improved PAH, decelerated bone age advancement and growth velocity. Most girls achieved adult height within target range, surpassing PAH at treatment initiation. Lesser anthropometric, sexual, skeletal maturity, lower baseline FSH, estradiol, longer treatment duration, less advanced BA at stopping GnRHa may translate into better adult height outcomes.

Therapeutic effects of melatonin in female mice with central precocious puberty by regulating the hypothalamic Kiss-1/Kiss1R system.

In recent years, central precocious puberty (CPP) in children is becoming more common, which seriously affects their physical and psychological health and requires finding a safe and effective treatment method. The aim of this study was to investigate the therapeutic effect of melatonin on CPP. A CPP model was established by subcutaneous injection of 300 micrograms of danazol into 5-day-old female mice, followed by treatment with melatonin and leuprolide. The vaginal opening was checked daily. Mice were weighed, gonads were weighed, gonadal index was calculated, and gonadal development was observed by hematoxylin and eosin (HE) staining. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) levels were measured by ELISA. By using RT-PCR and Western blotting, the mRNA and protein expression of the hypothalamus Kiss-1, Kiss-1 receptor (Kiss1R), gonadotropin-releasing hormone (GnRH), and pituitary GnRH receptor (GnRHR) were identified. The results showed that melatonin delayed vaginal opening time and reduced body weight, gonadal weight and indices in female CPP mice. Melatonin treatment prevents uterine wall thickening and ovarian luteinization in female CPP mice. Melatonin treatment reduces serum concentrations of FSH, LH, and E2 in female CPP mice. Melatonin suppressed the expressions of Kiss-1, Kiss1R and GnRH in the hypothalamus, and the expression of GnRHR in the pituitary of the female CPP mice. Our results suggest that melatonin can inhibit the hypothalamic-pituitary-gonadal (HPG) axis by down-regulating the Kiss-1/Kiss1R system, thereby treating CPP in female mice.

Gonadotropin-releasing hormone analogs treatment in girls with central precocious puberty and early fast puberty.

BACKGROUND: Gonadotropin-releasing hormone analog (GnRHa) is the standard treatment for children with central precocious puberty (CPP). We assessed efficacy and safety of GnRHa treatment in girls with CPP and early fast puberty (EFP). METHODS: This retrospective observational study included anthropometric, clinical and laboratory data retrieved from medical files of girls with CPP or EFP, treated with GnRHa and followed at a tertiary endocrine clinic during 2007-2021. RESULTS: For both CPP (n = 144) and EFP (n = 231) groups, mean height-SDS at GnRHa initiation and termination and at the last follow-up visit was greater than mid-parental height-SDS (P < 0.001). Only among girls with EFP, mean BMI-SDS was higher at treatment termination than initiation (P = 0.025). Median ages at menarche of the CPP and EFP groups were 11.8 and 12.0 years. Menstrual irregularities were reported in 20.3% of girls with CPP and in 18.7% of those with EFP. Adverse effects to treatment were reported in 3.5% and 3.9% of girls with CPP and EFP, respectively. CONCLUSIONS: In this large cohort, GnRHa treatment in girls with EFP was effective without significant adverse effects as in those with CPP. A randomized controlled trial is required to examine the psychological impact of GnRHa treatment of variant early puberty. IMPACT STATEMENT: Gonadotropin-releasing hormone analog (GnRHa) is the standard treatment for central precocious puberty (CPP). We assessed efficacy and safety of GnRHa treatment in girls with early fast puberty (EFP), characterized by pubertal signs between ages 8-9 years with fast pubertal signs advancement and accelerated growth and bone maturation and in girls with CPP. We found in this large cohort that GnRHa treatment in girls with EFP was effective and safe as in those with CPP. A prospective randomized controlled trial is required to examine the psychological impact of GnRHa treatment of variant early puberty.

Considerations on the improvement of height benefit in children with central precocious puberty / 中国当代儿科杂志

With the changes in various factors such as genetics and the environment, the incidence of childhood precocious puberty has been gradually increasing. Improving height is one of the key issues in the clinical management of precocious puberty. Currently, gonadotropin-releasing hormone analogs (GnRHa) remain the preferred treatment for precocious puberty, but their effect on height improvement is influenced by multiple factors, which may result in lower-than-expected height benefits. Combining recombinant human growth hormone (rhGH) therapy with GnRHa treatment is an alternative strategy to enhance the efficacy of GnRHa, but there is still no clear recommendation regarding the timing of their combination. Considering the current status of precocious puberty treatment, it is crucial to reevaluate the effects of GnRHa monotherapy and combination therapy with rhGH on height improvement. This article discusses strategies such as combination therapy indications to guide clinical medication and help children with precocious puberty achieve optimal height benefits.

Correlation between serum vitamin D level and uterine volume in girls with idiopathic central precocious puberty.

OBJECTIVES: Investigate serum vitamin D (vit D) levels' relation to uterine volume in idiopathic central precocious puberty (ICPP) girls and compare findings with normal peers. METHODS: Analyzed 278 ICPP cases from January 2017 to September 2022 alongside 239 normally developing girls. Collected clinical data and lab markers and performed subgroup analysis based on vit D levels. Correlation and regression analyses were conducted. RESULTS: The ICPP group exhibited elevated uterine volume and lower serum vit D compared to controls (p<0.05). A weak negative correlation was noted between vit D and uterine volume in ICPP (r=-0.193, p=0.004), and no such correlation in controls (r=-0.073, p=0.319). The ICPP vit D deficiency subgroup displayed higher uterine volume than the insufficiency and sufficiency subgroups (p<0.05). Uterine volume in the insufficiency subgroup exceeded the sufficiency subgroup (p<0.05). After adjusting for confounders, lower vit D is linked to increased ICPP uterine volume (non-standardized regression coefficient ß=-25.55, 95 % CI= -46.23, -4.87, p=0.016). A Limited correlation between vit D and uterine volume was seen in girls with normal pubertal timing. CONCLUSIONS: We demonstrated a correlation between vit D and uterine volume in ICPP girls, absent in normal peers. ICPP girls often exhibit lower vit D levels and increased uterine volume. Further research is vital for understanding vit D's role in ICPP pathogenesis and guiding prevention and treatment strategies.

Long-term health consequences of central precocious/early puberty (CPP) and treatment with Gn-RH analogue: a short update.

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.