One-year treatment with gonadotropin-releasing hormone analogues does not affect body mass index, insulin sensitivity or lipid profile in girls with central precocious puberty

Andrea J. Arcari 1 , Analía V. Freire 1 , María E. Escobar 1 , María G. Ballerini 1 , María G. Ropelato 1 , Ignacio Bergadá 1  and Mirta G. Gryngarten 1
  • 1 Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET – FEI – División de Endocrinología, Hospital de Niños Dr. Ricardo Gutiérrez, Gallo, Buenos Aires, Argentina
Andrea J. Arcari
  • Corresponding author
  • Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET – FEI – División de Endocrinología, Hospital de Niños Dr. Ricardo Gutiérrez, Gallo, Buenos Aires, Argentina
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, Analía V. Freire
  • Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET – FEI – División de Endocrinología, Hospital de Niños Dr. Ricardo Gutiérrez, Gallo, Buenos Aires, Argentina
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, María E. Escobar
  • Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET – FEI – División de Endocrinología, Hospital de Niños Dr. Ricardo Gutiérrez, Gallo, Buenos Aires, Argentina
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, María G. Ballerini
  • Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET – FEI – División de Endocrinología, Hospital de Niños Dr. Ricardo Gutiérrez, Gallo, Buenos Aires, Argentina
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, María G. Ropelato
  • Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET – FEI – División de Endocrinología, Hospital de Niños Dr. Ricardo Gutiérrez, Gallo, Buenos Aires, Argentina
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, Ignacio Bergadá
  • Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET – FEI – División de Endocrinología, Hospital de Niños Dr. Ricardo Gutiérrez, Gallo, Buenos Aires, Argentina
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and Mirta G. Gryngarten
  • Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET – FEI – División de Endocrinología, Hospital de Niños Dr. Ricardo Gutiérrez, Gallo, Buenos Aires, Argentina
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Abstract

Background

Puberty is associated with a physiological decline in insulin sensitivity (IS). Overweight (OW) and obesity (OB) are common among girls with central precocious puberty (CPP). CPP is considered a risk factor for metabolic diseases. The aim of this study was to assess surrogate measures of IS, body mass index (BMI) and other metabolic parameters in CPP girls at diagnosis and during treatment with gonadotropin-releasing hormone analogues (GnRHa).

Methods

We present a prospective longitudinal study of CPP girls. The standard oral glucose tolerance test, homeostatic model assessment of insulin resistance (HOMA-IR), whole-body IS index (ISI) and fasting lipid profiles were evaluated at diagnosis, and at 6 and 12 months of treatment.

Results

Nineteen CPP girls were included; 17 were evaluable. At baseline, seven patients had normal weight (NW), five were OW and five were OB. During GnRHa treatment no significant changes were observed in BMI, HOMA-IR or ISI when considering the whole group. Whereas, when we analyzed patients according to BMI status, in NW patients, BMI increased significantly with no changes in HOMA-IR or ISI along treatment. In the OW/OB group, no significant differences were observed in BMI, HOMA-IR or ISI.

Conclusions

Girls with CPP showed a high frequency of OW/OB and a high prevalence of IR. GnRHa did not affect BMI, IS or the lipid profile when considering the whole cohort of patients. However, there was an increase in BMI in NW girls but not in OW/OB patients.

  • 1.

    Parent AS, Franssen D, Fudvoye J, Gérard A, Bourguignon JP. Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: revision of human observations and mechanistic insight from rodents. Front Neuroendocrinol 2015;38:12–36.

    • Crossref
    • PubMed
    • Export Citation
  • 2.

    Goran MI, Gower BA. Longitudinal study on pubertal insulin resistance. Diabetes 2001;50:2444–50.

    • Crossref
    • PubMed
    • Export Citation
  • 3.

    Palmert MR, Mansfield MJ, Crowley Jr WF, Crigler Jr JF, Crawford JD, et al. Is obesity an outcome of gonadotropin-releasing hormone agonist administration? Analysis of growth and body composition in 110 patients with central precocious puberty. J Clin Endocrinol Metab 1999;84:4480–8.

    • PubMed
    • Export Citation
  • 4.

    Paterson WF, McNeill E, Young D, Donaldson MD. Auxological outcome and time to menarche following long-acting goserelin therapy in girls with central precocious or early puberty. Clin Endocrinol (Oxf) 2004;61:626–34.

    • Crossref
    • PubMed
    • Export Citation
  • 5.

    Traggiai C, Perucchin PP, Zerbini K, Gastaldi R, De Biasio P, et al. Outcome after depot gonadotrophin-releasing hormone agonist treatment for central precocious puberty: effects on body mass index and final height. Eur J Endocrinol 2005;153:463–4.

    • Crossref
    • PubMed
    • Export Citation
  • 6.

    Tascilar ME, Bilir P, Akinci A, Kose K, Akcora D, et al. The effect of gonadotropin-releasing hormone analog treatment (leuprolide) on body fat distribution in idiopathic central precocious puberty. Turk J Pediatr 2011;53:27–33.

    • PubMed
    • Export Citation
  • 7.

    Arcari AJ, Gryngarten MG, Freire AV, Ballerini MG, Ropelato MG, et al. Body mass index in girls with idiopathic central precocious puberty during and after treatment with GnRH analogues. J Pediatr Endocrinol 2016;15:1–7.

  • 8.

    Garn SM, LaVelle M, Rosenberg KR, Hawthorne VM. Maturational timing as a factor in female fatness and obesity. Am J Clin Nutr 1986;43:879–83.

    • Crossref
    • PubMed
    • Export Citation
  • 9.

    Lakshman R, Forouhi N, Luben R, Bingham S, Khaw K, et al. Association between age at menarche and risk of diabetes in adults: results from the EPIC-Norfolk cohort study. Diabetology 2008;51:781–6.

    • Crossref
    • Export Citation
  • 10.

    Lakshman R, Forouhi NG, Sharp SJ, Luben R, Bingham SA, et al. Early age at menarche associated with cardiovascular disease and mortality. J Clin Endocrinol Metab 2009;94:4953–60.

    • Crossref
    • PubMed
    • Export Citation
  • 11.

    Golub MS, Collman GW, Foster PM, Kimmel CA, Rajpert-De Meyts E, et al. Public health implications of altered puberty timing. Pediatrics 2008;121(Suppl 3):S218–30.

    • Crossref
    • PubMed
    • Export Citation
  • 12.

    Remsberg KE, Demerath EW, Schubert CM, Chumlea WC, Sun SS, et al. Early menarche and the development of cardiovascular disease risk factors in adolescent girls: the Fels Longitudinal Study. J Clin Endocrinol Metab 2005;90:2718–2724.

    • Crossref
    • PubMed
    • Export Citation
  • 13.

    Raitakari OT, Porkka KV, Rönnemaa T, Knip M, Uhari M, et al. The role of insulin in clustering of serum lipids and blood pressure in children and adolescents. The Cardiovascular Risk in Young Finns Study. Diabetologia 1995;38:1042–1050.

    • Crossref
    • PubMed
    • Export Citation
  • 14.

    Boot AM, De Muinck K-SS, Pols HA, Krenning EP, Drop SL. Bone mineral density and body composition before and during treatment with gonadotropin-releasing hormone agonist in children with central precocious and early puberty. J Clin Endocrinol Metab 1998;83:370–3.

    • PubMed
    • Export Citation
  • 15.

    Feuillan P, Jones J, Barnes K, Oerter-Klein K, Cutler Jr G. Reproductive axis after discontinuation of gonadotropin-releasing hormone analog treatment of girls with precocious puberty: long term follow-up comparing girls with hypothalamic hamartoma to those with idiopathic precocious puberty. J Clin Endocrinol Metab 1999;84:44–9.

    • Crossref
    • PubMed
    • Export Citation
  • 16.

    Chiumello G, Brambilla P, Guarneri MP, Russo G, Manzoni P, et al. Precocious puberty and body composition: effects of GnRH analog treatment. J Pediatr Endocrinol Metab 2000;13(Suppl 1):791–4.

    • PubMed
    • Export Citation
  • 17.

    Chiocca E, Dati E, Baroncelli GI, Mora S, Parrini D, et al. Body mass index and body composition in adolescents treated with gonadotropin-releasing hormone analogue triptorelin depot for central precocious puberty: data at near final height. Neuroendocrinology 2009;89:441–7. DOI: 10.1159/000197862. Epub 2009 Jan 29.

    • Crossref
    • PubMed
    • Export Citation
  • 18.

    Anık A, Çatlı G, Abacı A, Böber E. Effect of gonadotropin-releasing hormone agonist therapy on body mass index and growth in girls with idiopathic central precocious puberty. Indian J Endocrinol Metab 2015;19:267–71.

    • Crossref
    • PubMed
    • Export Citation
  • 19.

    Heger S, Partsch CJ, Sippell WG. Long-term outcome after depot gonadotropin releasing hormone agonist treatment of central precocious puberty: final height, body proportions, body composition, bone mineral density, and reproductive function. J Clin Endocrinol Metab 1999;84:4583–90.

    • PubMed
    • Export Citation
  • 20.

    Lazar L, Kauli R, Pertzelan A, Phillip M. Gonadotropin-suppressive therapy in girls with early and fast puberty affects the pace of puberty but not total pubertal growth or final height. J Clin Endocrinol Metab 2002;87:2090–4.

    • Crossref
    • PubMed
    • Export Citation
  • 21.

    Glab E, Barg E, Wikiera B, Grabowski M, Noczyńska A. Influence of GnRH analog therapy on body mass in central precocious puberty. Pediatr Endocrinol Diabetes Metab 2009;15:7–11.

    • PubMed
    • Export Citation
  • 22.

    Ko JH, Lee HS, Lim JS, Kim SM, Hwang JS. Changes in bone mineral density and body composition in children with central precocious puberty and early puberty before and after one year of treatment with GnRH agonist. Horm Res Paediatr 2011;75:174–9.

    • Crossref
    • PubMed
    • Export Citation
  • 23.

    van der Sluis IM, Boot AM, Krenning EP, Drop SL, de Muinck Keizer-Schrama SM. 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. J Clin Endocrinol Metab 2002;87:506–12.

    • Crossref
    • PubMed
    • Export Citation
  • 24.

    Arrigo T, De Luca F, Antoniazzi F, Galluzzi F, Segni M, et al. Reduction of baseline body mass index under gonadotropin-suppressive therapy in girls with idiopathic precocious puberty. Eur J Endocrinol 2004;150:533–7.

    • PubMed
    • Export Citation
  • 25.

    Poomthavorn P, Suphasit R, Mahachoklertwattana P. Adult height, body mass index and time of menarche of girls with idiopathic central precocious puberty after gonadotropin-releasing hormone analogue treatment. Gynecol Endocrinol 2011;27:524–8.

    • Crossref
    • PubMed
    • Export Citation
  • 26.

    Sorensen K, Mouritsen A, Mogensen SS, Aksglaede L, Juul A. IS and lipid profiles in girls with central precocious puberty before and during gonadal suppression. J Clin Endocrinol Metab 2010;95:3736–3744.

    • Crossref
    • PubMed
    • Export Citation
  • 27.

    Colmenares A, Gunczler P, Lanes R. Higher prevalence of obesity and overweight without an adverse metabolic profile in girls with central precocious puberty compared to girls with early puberty, regardless of GnRH analogue treatment. Int J Pediatr Endocrinol 2014;2014:5. DOI: 10.1186/1687-9856-2014–5.

    • Crossref
    • PubMed
    • Export Citation
  • 28.

    Park J, Kim JH. Change in body mass index and insulin resistance after 1-year treatment with gonadotropin-releasing hormone agonists in girls with central precocious puberty. Ann Pediatr Endocrinol Metab 2017;22:27–35.

    • Crossref
    • PubMed
    • Export Citation
  • 29.

    Freire AV, Gryngarten MG, Ballerini MG, Arcari AJ, Escobar ME, et al. Assessment of estradiol response after depot triptorelin administration in girls with central precocious puberty. Horm Res Paediatr 2016;85:58–64.

    • Crossref
    • PubMed
    • Export Citation
  • 30.

    Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in girls. Arch Dis Child 1969;44:291–303.

    • Crossref
    • PubMed
    • Export Citation
  • 31.

    Greulich WW, Pyle SI. Radiographic atlas of skeletal development of the hand and wrist, 2nd ed. Palo Alto, CA: Stanford University Press; 1959.

  • 32.

    Cole TJ, Bellizi MC, Fiegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: international survey. Br Med J 2000;320:1240–3.

    • Crossref
    • Export Citation
  • 33.

    Browning L, Hsieh S, Ashwell M. A systematic review of waist-to-height ratio as a screening tool for the prediction of cardiovascular disease and diabetes: 0.5 could be a suitable global boundary value. Nutr Res Rev 2010; 23:247–69.

    • Crossref
    • PubMed
    • Export Citation
  • 34.

    Ballerini MG, Bergadá I, Rodríguez ME, Keselman A, Bengolea VS, et al. Insulin level and IS indices among healthy children and adolescents. Arch Argent Pediatr 2016;114:329–36.

    • PubMed
    • Export Citation
  • 35.

    Matsuda M, DeFronzo RA. IS indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999;22:1462–70.

    • Crossref
    • PubMed
    • Export Citation
  • 36.

    Arancibia C, Galgani J, Valderas JP, Morales M, Santos JL, et al. Evaluation of serum insulin levels after an oral glucose load for the diagnosis of insulin resistance Rev Med Chile 2014;142:1106–12.

  • 37.

    Araujo MB, Casavalle P, Tonietti M, Ozuna B, Andres ME, et al. Comité de nutrición: Consensus on management of dyslipidemia in pediatrics. Arch Argent Pediatr 2015;13:177–86.

  • 38.

    Stumvoll M, Mitrakou A, Pimenta W, Jenssen T, Yki-Järvinen H, et al. Use of the oral glucose tolerance test to assess insulin release and IS. Diabetes Care 2000;23:295–301.

    • Crossref
    • PubMed
    • Export Citation
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The Journal of Pediatric Endocrinology and Metabolism (JPEM) is the only international journal dedicated exclusively to endocrinology in the neonatal, pediatric and adolescent age groups, and publishes the results of clinical investigations in pediatric endocrinology and basic research. JPEM publishes Review Articles, Original Research, Case Reports, Short Communications and Letters to the Editor.

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