The Side Effects of Gonadotropin Releasing Hormone Analog (Diphereline) in Treatment of Idiopathic Central Precocious Puberty
Treatment of central precocious puberty (CPP) is the administration of GnRH analogs. Metabolic syndrome comprised metabolic disturbances that confer increased risk of (CVD) diabetes mellitus (DM) and cardiovascular disease. This study is a longitudinal prospective study in pediatric endocrinology clinic. 30 non-obese children with idiopathic CPP were involved. Total body weight, height, blood pressure, BMI and waist circumference of the patients along with their triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), fasting plasma sugar (FPS) were evaluated at the beginning and during 3 and 6 months GnRH analog therapy. All of the patients involved in this study were female with age 9.5±1.02 years. Waist circumference, weight and BMI were 69.3 cm, 37.21 kg, and 19.13 kg/cm2 before therapy and 72.25 cm, 40.11 kg, and 19.54 kg/m2 6 months after therapy respectively. Mean systolic and diastolic blood pressure of the patients before therapy was 96.83 mmHg, 66mmHg and after 6 months therapy was 98.66 mmHg, 89.63 mmHg respectively. Mean TG, LDL, HDL and FPS were 90.06 mg/dl, 91.6 mg/dl, 43.7 mg/dl and 89.6 mg/dl before therapy and 96.4 mg/dl, 93.1 mg/dl, 44.7 mg/dl and 91.36 after 6 months therapy respectively. GnRH analog therapy doesn't cause metabolic syndrome after 3 and 6 month therapy but it may cause hyperlipidemia and central obesity.
Mul D, Hughes IA. The use of GnRH agonists in precocious puberty. Eur J Endocrinol 2008;159(Suppl1):S3-8.
Bramswig J, Dubbers A. Disorders of pubertal development. Dtsch Arztebl Int 2009;106(17):295-303.
Prete G, Couto-Sliva AC, Trivin C, Brauner R. Idiopathic central precocious puberty I girls: presentation factors. BMC Pediatr 2008;8:27.
Carel JC, Leger J. Clinical practice. Precocious puberty. NEngl J Med 2008;358:2366-77.
Kaplowitz P. Clinical characteristics of 104 children referred for evaluation of precocious puberty. J Clin Endocrinol Metab 2004;89:3644-50.
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(12):4583-90.
Carel JC, Lahlou N, Roger M, Chaussain JL. Precocious puberty and statural growth. Hum Reprod Update 2004;10(2):135-47.
van der Sluis IM, Boot AM, Krening EP, Drop SL, de Muinck KS. 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(2):506-12.
Partsch JC, Heger S, Sippell WG. Management and outcome of central precocious puberty. Clin Endocrinol 2002;56:129-48
Magiakou MA, Manousaki D, Papadaki M, Hadjidakis D, Levidou G, Vakaki M, Papaefstathiou A, Lalioti N, Kanaka-Gantenbein C, Piaditis G, Chrousos GP, Dacou- Voutetakis C. The efficacy and safety of gonadotropinreleasing hormone analog treatment in childhood and adolescence: a single center, long-term follow-up study. J Clin Endocrinol Metab 2010;95(1):109-17.
Tung YC, Lee JS, Tsai WY, Hsiao PH. The effects of gonadotropin releasing hormone analogue therapy on girls with gonadotropin-dependent precocious puberty. J Forms Med Assoc 2007;106(10):826-31.
Giab E, Barg E, Wikiera B, Grabowski M, Noczynska A. Influence of GnRH analog therapy on body mass in central precocious puberty. Pediatr Endocrinol Diabetes Metab 2009;15(1):7-11.
Carel JC, Eugster EA, Rogol A, Ghizzoni L, Palmert MR. ESPE-LWPES GnRH Analogs Consensus Conference Group, Antoniazzi F, Berenbaum S, Bourguignon JP, Chrousos GP, Coste J, Deal S, de Vries L, Foster C, Heger S, Holland J, Jahnukainen K, Juul A, Kaplowitz P, Lahlou N, Lee MM, Lee P, Merke DP, Neely EK, Oostdijk W, Phillip M, Rosenfield RL, Shulman D, Styne D, Tauber M, Wit JM. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics 2009;123(4):e752-62.
Chiocca E, Dati E, Baroncelli GI, Mora S, Parrini D, Erba P, Bertelloni S. 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. Neuroendocriology 2009;89(4):441-7.
Arrigo T, De Luca F, Antoniazzi F, Galluzzi F, Segni M, Rosano M, Messina MF, Lombardo F. Reduction of baseline body mass index under gonadotropin-suppressive therapy in girls with idiopathic precocious puberty. Eur J Endocrinol 2004;150(4):533-7.
Oostdijk W, Rikken B, Schreuder S, Otten B, Odink R, Rouwé C, Jansen M, Gerver WJ, Waelkens J, Drop S. Final height in central precocious puberty after long term treatment with a slow release GnRH agonist. Arch Dis Child 1996;75(4):292-7.
Paul D, Conte FA, Grumbach MM, Kaplan SL. Long term effect of goadotropin-releasing hormone agonist therapy on final and near-final height in 26 children with true precocious puberty treated at a median age of less than 5 years. J Clin Endocrinol Metabol 1995;80(2):546-51.
Boot AM, de Muinck KS, 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 puberty and early puberty. J Clin Endocrinol Metab 1998;83(2):370-3.
Feuillan PP, Jones JV, Barnes K, Oerter KK, Cutler GB. Reproductive axis after discontinuation of gonadotropinreleasing 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 Metabol 1999;84(1):44-9.
Palmert MR, Mansfield MJ, Crowley WF, Crigler JF, Crawford JD, Boepple PA. Is obesity and 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(12):4480-8.
Kronenberg HM, Melmed Sh, Polonsky KS, Larsen PR. Williams textbook of endocrinology. 11th ed Saunders; 2008.
de Ferranti SD, Gauvreau K, Ludwig DS, Neufeld EJ, Newburger JW, Rifai N. Prevalence of the metabolic syndrome in American adolescents. Findings from the Third National Health and Nutrition Examination Survey. Circulation 2004;110(16):2494-7.
Tascilar ME, Bilir P, Akinci A, Kose K, Akoca D, Inceoglu D, Fitoz SO. The effect of Gonadotropin- Releasing Hormone Analog treatment (leuprolide) on body fat Distribution in idiopathic central precocious puberty. Tur J Pediatr 2011;53(1):27-33.
Johansson T, Ritzen EM. Very long-term follow-up of girls with early and late menarche. Endocr Dev 2005;8:126-36.
Pasquino Am, Pucarelli I, Accardo F, Demiraj V, Segni M, Di Nardo R. Long-term observation of 87 girls with idiopathic central precocious puberty treated with gonadotropin-releasing hormone analogs: Impact on adult height, body mass index, bone mineral content, and reproductive function. J Clin Endocrinol Metab 2008;93(1):190-5
Smith MR, Lee H, MC Govern F, Fallon MA. Metabolic changes during gonadotropin-releasing hormone agonist therapy for prostate cancer: differences from the classic metabolic syndrome. Cancer. 2008;112(10): 2188-94.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.