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      The Effect of GnRHa Treatment on Body Mass Index in Central Precocious Puberty: A Systematic Review and Meta-Analysis

      , , , , ,
      Hormone Research in Paediatrics
      S. Karger AG

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          Abstract

          <b><i>Background:</i></b> Recently, numerous studies have addressed the long-term effects of treatment with gonadotropin-releasing hormone analog (GnRHa) in patients with central precocious puberty (CPP). However, the effects of GnRHa treatment on body mass index (BMI) in patients with CPP remain controversial. <b><i>Objective:</i></b> This systematic review and meta-analysis aimed to evaluate the association between GnRHa treatment and BMI in patients with CPP. <b><i>Methods:</i></b> A systematic search of databases, PubMed, EMBASE, and Web of Science published before August 2021 identified relevant studies. The overall effect analysis was performed using STATA version statistical software 15.0. <b><i>Results:</i></b> The study included a total of 28 studies. At the end of GnRHa treatment, the BMI-standard deviation score (BMI-SDS) was greater than baseline BMI-SDS (weighted mean difference (WMD) = 0.14, 95% CI: 0.04–0.23; <i>p</i> = 0.004), especially in girls with CPP (WMD = 0.15, 95% CI: 0.05–0.25; <i>p</i> = 0.005) and in patients with normal weight (WMD = 0.34, 95% CI: 0.19–0.48, <i>p</i> &lt; 0.001). After reaching adult height, BMI-SDS returned to baseline, suggesting that the effect of GnRHa treatment on BMI would disappear as the child grew (WMD = −0.03, 95% CI: −0.39 to 0.32; <i>p</i> = 0.815). <b><i>Conclusion:</i></b> For patients with CPP, while treatment with GnRHa may increase the BMI in the short term after treatment, the BMI is likely to return to normal when the patients reach adult height.

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          Causes, diagnosis, and treatment of central precocious puberty.

          Central precocious puberty results from the premature activation of the hypothalamic-pituitary-gonadal axis. It mimics physiological pubertal development, although at an inappropriate chronological age (before 8 years in girls and 9 years in boys). It can be attributable to cerebral congenital malformations or acquired insults, but the cause in most cases in girls remains unknown. MKRN3 gene defects have been identified in familial disease, with important basic and clinical results. Indeed, genetic analysis of this gene should be included in the routine clinical investigation of familial and idiopathic cases of central precocious puberty. Gonadotropin-releasing hormone agonists are the gold-standard treatment. The assessment and management of this disease remain challenging for paediatric endocrinologists. In this Series paper, we describe current challenges involving the precise diagnosis and adequate treatment of this disorder.
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            Consensus statement on the use of gonadotropin-releasing hormone analogs in children.

            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. 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. 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. 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. 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.
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              Worldwide Secular Trends in Age at Pubertal Onset Assessed by Breast Development Among Girls: A Systematic Review and Meta-analysis

              Has the age at onset of thelarche in girls changed within the past 4 decades? This systematic review and meta-analysis found that age at pubertal onset, with thelarche assessed by physical or clinical examination of the breast, decreased by a mean of almost 3 months per decade from 1977 to 2013. In most textbooks, thelarche among girls younger than 8 years is considered pathologic and warrants further investigations; therefore, a younger age at thelarche in girls in the general population will change current diagnostic decision-making in girls suspected to have puberty disorders. The initial clinical sign of pubertal onset in girls is breast gland development (thelarche). Although numerous studies have used recalled age at menarche (first menstruation) to assess secular trends of pubertal timing, no systematic review has been conducted of secular trends of thelarche. To systematically evaluate published data on pubertal timing based on age at thelarche and evaluate the change in pubertal onset in healthy girls around the world. A systematic literature search was performed in PubMed and Embase of all original peer-reviewed articles published in English before June 20, 2019. Included studies used clinical assessment of breast development in healthy girls and used adequate statistical methods, including the reporting of SEs or CIs. The quality of the articles was evaluated by assessing study design, potential sources of bias, main characteristics of the study population, and methods of statistical analysis. In accordance with PRISMA guidelines, all articles were assessed for eligibility independently by 2 authors. Weighted regression analysis was performed using a random-effects model. Studies examining age at thelarche (development of Tanner breast stage 2) in healthy girls. The literature search resulted in a total of 3602 studies, of which 30 studies fulfilled the eligibility criteria. There was a secular trend in ages at thelarche according to race/ethnicity and geography. Overall, the age at thelarche decreased 0.24 years (95% CI, −0.44 to −0.04) (almost 3 months) per decade from 1977 to 2013 ( P  = .02). The age at thelarche has decreased a mean of almost 3 months per decade from 1977 to 2013. A younger age at pubertal onset may change current diagnostic decision-making. The medical community needs current and relevant data to redefine “precocious puberty,” because the traditional definition may be outdated, at least in some regions of the world. This systematic review and meta-analysis evaluates published data on pubertal timing based on age at thelarche and evaluates the change in pubertal onset in healthy girls around the world.
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                Author and article information

                Journal
                Hormone Research in Paediatrics
                Horm Res Paediatr
                S. Karger AG
                1663-2818
                1663-2826
                January 5 2024
                : 1-14
                Article
                10.1159/000535132
                89c8959b-5f2a-4aec-9c43-50ce15625f9a
                © 2024

                https://creativecommons.org/licenses/by-nc/4.0/

                https://creativecommons.org/licenses/by-nc/4.0/

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