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      Body mass index in girls with idiopathic central precocious puberty during and after treatment with GnRH analogues

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          Abstract

          Background

          In girls with Idiopathic Central Precocious Puberty (ICPP) concern has been raised by the potential impact of GnRH-analogues (GnRHa) treatment on body weight. We evaluated the effect of GnRHa on Body Mass Index (BMI) in girls with ICPP according to weight status at diagnosis.

          Methods

          One hundred seventeen ICPP girls were divided according to pretreatment weight status in: normal weight (NW), overweight (OW) and obese (OB). BMI at one and two years of treatment was assessed. BMI-SDS of 60 patients who reached adult height (AH) was compared to that of 33 ICPP untreated girls.

          Results

          NW girls significantly increased their baseline BMI-SDS at 1 and 2 years of treatment. OW girls only had a significant increment at one year of treatment while OB girls showed no BMI-SDS change. Patients evaluated at AH (at least four years after GnRHa withdrawal) showed a significant decrease on BMI compared to baseline and a significantly lower BMI than the untreated group.

          Conclusion

          In ICPP girls the BMI increase under GnRHa was inversely related to the pretreatment weight status. In the long term follow-up, no detrimental effect of GnRHa on body weight was observed. BMI-SDS was lower in treated than in untreated girls.

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          Most cited references21

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          The efficacy and safety of gonadotropin-releasing hormone analog treatment in childhood and adolescence: a single center, long-term follow-up study.

          The objective of the study was to evaluate the long-term effect of GnRH analog (GnRHa) treatment on final height (FH), body mass index (BMI), body composition, bone mineral density (BMD), and ovarian function. Ninety-two females, evaluated in adulthood, were categorized as follows: group A, 47 girls with idiopathic central precocious puberty (33 GnRHa treated and 14 nontreated); group B, 24 girls with isolated GH deficiency (15 GnRHa and GH treated and nine GH treated); group C, 21 girls with idiopathic short stature (seven GnRHa and GH treated, seven GnRHa treated, and seven nontreated). FH, BMD, and percent fat mass of GnRHa-treated patients in all three groups were comparable with those of the respective nontreated subjects. BMI values of GnRHa-treated and nontreated subjects in groups A and C were comparable, whereas in group B, a higher BMI was found in subjects treated only with GH. Nontreated patients with ICPP had greater maximal ovarian volumes, higher LH and LH to FSH ratio, and more severe hirsutism than GnRHa-treated ones. Menstrual cycle characteristics were not different between treated and nontreated subjects. The prevalence of polycystic ovary syndrome in treated and untreated girls with ICPP was comparable, whereas in the entire cohort, it was 11.1% in GnRHa treated and 32.1% in the untreated (P = 0.02). Girls treated in childhood with GnRHa have normal BMI, BMD, body composition, and ovarian function in early adulthood. FH is not increased in girls with ICPP in whom GnRHa was initiated at about 8 yr. There is no evidence that GnRHa treatment predisposes to polycystic ovary syndrome or menstrual irregularities.
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            Gonadotropin-suppressive therapy in girls with early and fast puberty affects the pace of puberty but not total pubertal growth or final height.

            Early and fast puberty (EFP) in girls, defined as pubertal onset at age 8-9 yr, with an accelerated course, may cause compromised final height (FHt) and psychosocial distress. Treatment with a gonadotropin-suppressive agent is controversial, because the improvement in FHt is equivocal and there may be risk of obesity. We analyzed the data of 126 girls with EFP: 63 treated with GnRH analog (GnRHA) since Tanner stage 3, for 2-4 yr; and 63 untreated. Age at onset of puberty; accelerated time of transition from Tanner stage 2 to 3 (<1.3 yr); and clinical, hormonal and sonographic findings were similar in the 2 groups. The girls given GnRHA treatment had a significantly prolonged pubertal course, compared with the accelerated course in the untreated girls (4.7 +/- 0.4 vs. 2.45 +/- 0.4 yr, P < 0.001). After therapy, they reached Tanner stages 4 and 5 and FHt at a significantly older age than the untreated group (P < 0.001), and their menarche was delayed (12.8 +/- 0.6 vs. 10.8 +/- 0.5 yr, P < 0.001). However, the different pace of puberty in the 2 groups did not change the total pubertal growth and the bone maturation rate. The Ht gain from Tanner stage 3 to 4 (10.4 +/- 2.7 vs. 11.2 +/- 3.1 cm) and from Tanner stage 4 to FHt (8.2 +/- 2.7 vs. 8.8 +/- 3.6 cm) was similar in the treated and untreated girls, as were absolute Ht and bone age at each pubertal stage. The weight gain of the treated girls was more pronounced during treatment (P = 0.0016), but it was arrested after discontinuation of therapy; and by the time FHt was reached, the body mass index was similar in the 2 groups. The treated and untreated girls achieved a similar mean FHt, which was not significantly different from their respective mean target Ht (THt). Individual analysis revealed that 70% of the treated girls and 67% of the untreated girls attained their THt range (THt +/- 0.5 SD) or surpassed it. In conclusion, treatment with GnRHA affected only the pace of EFP. The similar Ht gain and bone maturation rate at each pubertal stage in the treated and untreated girls may suggest that the total pubertal growth is not dependent on pubertal duration and pace and is probably determined already at the onset of the normal pubertal development. The treatment did not compromise the FHt and did not cause long-lasting obesity. Therefore, GnRHA therapy may be suggested for use in girls who have psychosocial difficulties in coping with EFP.
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              Longitudinal follow-up of bone density and body composition in children with precocious or early puberty before, during and after cessation of GnRH agonist therapy.

              We studied bone mineral density (BMD), bone metabolism, and body composition in 47 children with central precocious puberty (n = 36) or early puberty (n = 11) before, during, and after cessation of GnRH agonist. Bone density and body composition were measured with dual energy x-ray absorptiometry and expressed as SD scores. Bone age and biochemical parameters of bone turnover were assessed. Measurements were performed at baseline, after 6 months, and on a yearly basis thereafter. Mean lumbar spine BMD SD scores for chronological age were significantly higher than zero at baseline and decreased during treatment. Lumbar spine bone mineral apparent density and total body BMD did not differ from normal at baseline and showed no significant changes during treatment. In contrast, BMD SD scores for bone age were significantly lower than zero at baseline and at cessation of therapy. Two years after therapy, bone mineral apparent density and BMD SD scores for bone age and chronological age did not differ from normal. Markers of bone turnover decreased during treatment, mainly in the first 6 months. Patients had increased percentage of fat and lean body mass at baseline. After an initial increase of percentage body fat during treatment, percentage body fat decreased and normalized within 1 yr after cessation of treatment. Our longitudinal analysis suggests that peak bone mass or body composition will not be impaired in patients with precocious or early puberty after GnRH agonist therapy.
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                Author and article information

                Contributors
                (+54-11) 4963-5931 , aarcari@cedie.org.ar , ajarcari@hotmail.com
                mgryngarten@cedie.org.ar
                freireav@yahoo.com.ar
                mgballerini@cedie.org.ar
                gropelato@cedie.org.ar
                ibergada@cedie.org.ar
                meugeniaescobar@cedie.org.ar
                Journal
                Int J Pediatr Endocrinol
                Int J Pediatr Endocrinol
                International Journal of Pediatric Endocrinology
                BioMed Central (London )
                1687-9848
                1687-9856
                5 August 2016
                5 August 2016
                2016
                : 2016
                : 15
                Affiliations
                Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET – FEI – División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Gallo 1330, C1425EFD Buenos Aires, Argentina
                Article
                33
                10.1186/s13633-016-0033-7
                4974749
                27499763
                65ed518e-4e5b-4f64-bfd0-ed8f54d19c8a
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 18 May 2016
                : 26 July 2016
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Pediatrics
                central precocious puberty,bmi,gnrh analogues
                Pediatrics
                central precocious puberty, bmi, gnrh analogues

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