Short-term effects of gonadotropin-releasing hormone analogue treatment on leptin, ghrelin and peptide YY in girls with central precocious puberty
-
Piyathida Wijarn
Abstract
Objectives
To determine appetite-regulating hormone levels in girls with central precocious puberty (CPP) before and after 20 weeks of gonadotropin-releasing hormone analogue (GnRH-A) treatment.
Methods
Eighteen newly diagnosed CPP girls were enrolled. Body composition measured by bioelectrical impedance analysis and GnRH-A test were performed with fasting serum leptin, ghrelin and peptide YY (PYY) measurements at baseline (before) and after 20 weeks of GnRH-A treatment.
Results
Following GnRH-A treatment, all patients had prepubertal gonadotropin and estradiol levels. Mean (SD) fat mass index (FMI) was significantly increased from 4.5 (1.7) to 5.0 (1.8) kg/m2 after treatment. Also, median (IQR) serum leptin level was significantly increased from 6.9 (4.2–8.6) to 7.4 (5.3–13.1) ng/mL. FMI had a positive correlation with serum leptin level (r=0.64, p=0.004). In contrast, no significant changes of serum ghrelin and PYY levels were observed.
Conclusions
Decreased estrogen following short-term GnRH-A treatment in CPP girls may cause an increase in appetite and consequently an elevation of FMI. Increased serum leptin may be a result of having increased FMI secondary to an increase in appetite.
Funding source: Mahidol University
Award Identifier / Grant number: Unassigned
Acknowledgment
This study was supported by a research grant from the Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. The authors have no competing interests.
Research funding: This study was supported by a research grant from The Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Author contributions: Concept: Piyathida Wijarn, Preamrudee Poomthavorn, Pat Mahachoklertwattana. Design: Piyathida Wijarn, Preamrudee Poomthavorn, Pat Mahachoklertwattana. Data Collection and Processing: Piyathida Wijarn, Patcharin Khlairit, Sarunyu Pongratanakul, Laor Chailurkit, Pat Mahachoklertwattana. Analysis and Interpretation: Piyathida Wijarn, Preamrudee Poomthavorn, Pat Mahachoklertwattana. Literature Search: Piyathida Wijarn, Preamrudee Poomthavorn, Pat Mahachoklertwattana. Writing: Piyathida Wijarn, Preamrudee Poomthavorn, Pat Mahachoklertwattana.
Competing interests: Authors state no conflict of interest.
Informed consent: A written informed consent was obtained from all patients and their legal guardians before the enrollment.
Ethical approval: Faculty of Medicine Ramathibodi Hospital, Mahidol University; Date: 21 Jan 2015, Number: MURA2015/15.
Peer-review: Internally peer-reviewed by all authors.
References
1. Grumbach, MM. The neuroendocrinology of human puberty revisited. Horm Res 2002;57(Suppl 2):2–14. https://doi.org/10.1159/000058094.Search in Google Scholar
2. Carel, JC, Leger, J. Clinical practice: precocious puberty. N Engl J Med 2008;358:2366–77. https://doi.org/10.1056/nejmcp0800459.Search in Google Scholar
3. Carel, JC, Eugster, EA, Rogol, A, Ghizzoni, L, Palmert, MR. ESPE-LWPES GnRH Analogs Consensus Conference Group. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics 2009;123:e752–62. https://doi.org/10.1542/peds.2008-1783.Search in Google Scholar
4. 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. https://doi.org/10.1210/jcem.87.2.8202.Search in Google Scholar
5. Wolters, B, Lass, N, Reinehr, T. Treatment with gonadotropin-releasing hormone analogues: different impact on body weight in normal-weight and overweight children. Horm Res Paediatr 2012;78:304–11. https://doi.org/10.1159/000346145.Search in Google Scholar
6. Su, PH, Wang, SL, Lin, CY, Chen, JY, Changlai, CP, Jian, SH, et al.. Leptin changes in Taiwanese girls with central precocious puberty before and during the GnRH agonist treatment. Acta Paediatr Taiwan 2005;46:278–83.Search in Google Scholar
7. Maffeis, C, Franceschi, R, Moghetti, P, Camilot, M, Lauriola, S, Tato, L. Circulating ghrelin levels in girls with central precocious puberty are reduced during treatment with LHRH analog. Eur J Endocrinol 2007;156:99–103. https://doi.org/10.1530/eje.1.02320.Search in Google Scholar
8. 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. https://doi.org/10.1210/jcem.84.12.6203.Search in Google Scholar
9. Palmert, MR, Mansfield, MJ, Crowley, WFJr, Crigler, JFJr, Crawford, JD, Boepple, PA. 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. https://doi.org/10.1210/jcem.84.12.6204.Search in Google Scholar
10. 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;93:190–5. https://doi.org/10.1210/jc.2007-1216.Search in Google Scholar
11. Gillis, D, Karavani, G, Hirsch, HJ, Strich, D. Time to menarche and final height after histrelin implant treatment for central precocious puberty. J Pediatr 2013;163:532–6. https://doi.org/10.1016/j.jpeds.2013.01.021.Search in Google Scholar
12. Lazar, L, Lebenthal, Y, Yackobovitch-Gavan, M, Shalitin, S, de Vries, L, Phillip, M, et al.. Treated and untreated women with idiopathic precocious puberty: BMI evolution, metabolic outcome, and general health between third and fifth decades. J Clin Endocrinol Metab 2015;100:1445–51. https://doi.org/10.1210/jc.2014-3748.Search in Google Scholar
13. 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. https://doi.org/10.1186/1687-9856-2014-5.Search in Google Scholar
14. Liang, Y, Wei, H, Li, J, Hou, L, Zhang, J, Wu, W, et al.. Effect of GnRHa 3.75 mg subcutaneously every 6 weeks on adult height in girls with idiopathic central precocious puberty. J Pediatr Endocrinol Metab 2015;28:839–46. https://doi.org/10.1515/jpem-2014-0305.Search in Google Scholar
15. Faienza, MF, Brunetti, G, Acquafredda, A, Delvecchio, M, Lonero, A, GaetaA, et al.. Metabolic outcome, bone health, and risk of polycystic ovary syndrome in girls with idiopathic central precocious puberty treated with gonadotropin-releasing hormone analogues. Horm Res Paediatr 2017;87:162–9. https://doi.org/10.1159/000456546.Search in Google Scholar
16. Hirschberg, AL. Sex hormones, appetite and eating behaviour in women. Maturitas 2012;71:248–56. https://doi.org/10.1016/j.maturitas.2011.12.016.Search in Google Scholar
17. Suzuki, K, Jayasena, CN, Bloom, SR. Obesity and appetite control. Exp Diabetes Res 2012;2012:824305. https://doi.org/10.1155/2012/824305.Search in Google Scholar
18. Comninos, AN, Jayasena, CN, Dhillo, WS. The relationship between gut and adipose hormones and reproduction. Hum Reprod Update 2014;20:153–74. https://doi.org/10.1093/humupd/dmt033.Search in Google Scholar
19. Garcia-Mayor, RV, Andrade, MA, Rios, M, Lage, M, Dieguez, C, Casanueva, FF. Serum leptin levels in normal children: relationship to age, gender, body mass index, pituitary-gonadal hormones, and pubertal stage. J Clin Endocrinol Metab 1997;82:2849–55. https://doi.org/10.1210/jcem.82.9.4235.Search in Google Scholar
20. Blum, WF, Englaro, P, Hanitsch, S, Juul, A, Hertel, NT, Muller, J, et al.. Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone. J Clin Endocrinol Metab 1997;82:2904–10. https://doi.org/10.1210/jcem.82.9.4251.Search in Google Scholar
21. Hassink, SG, Sheslow, DV, deLancey, E, Opentanova, I, Considine, RV, Caro, JF. Serum leptin in children with obesity: relationship to gender and development. Pediatrics 1996;98:201–3.10.1542/peds.98.2.201Search in Google Scholar
22. Soriano-Guillen, L, Barrios, V, Campos-Barros, A, Argente, J. Ghrelin levels in obesity and anorexia nervosa: effect of weight reduction or recuperation. J Pediatr 2004;144:36–42. https://doi.org/10.1016/j.jpeds.2003.10.036.Search in Google Scholar
23. Soriano-Guillen, L, Barrios, V, Chowen, JA, Sanchez, I, Vila, S, Quero, J, et al.. Ghrelin levels from fetal life through early adulthood: relationship with endocrine and metabolic and anthropometric measures. J Pediatr 2004;144:30–5. https://doi.org/10.1016/j.jpeds.2003.08.050.Search in Google Scholar
24. Roth, CL, Enriori, PJ, Harz, K, Woelfle, J, Cowley, MA, Reinehr, T. Peptide YY is a regulator of energy homeostasis in obese children before and after weight loss. J Clin Endocrinol Metab 2005;90:6386–91. https://doi.org/10.1210/jc.2005-1357.Search in Google Scholar
25. Lloyd, B, Ravi, P, Mendes, N, Klibanski, A, Misra, M. Peptide YY levels across pubertal stages and associations with growth hormone. J Clin Endocrinol Metab 2010;95:2957–62. https://doi.org/10.1210/jc.2009-2496.Search in Google Scholar
26. Lopez, M, Tena-Sempere, M. Estrogens and the control of energy homeostasis: a brain perspective. Trends Endocrinol Metab 2015;26:411–21. https://doi.org/10.1016/j.tem.2015.06.003.Search in Google Scholar
27. Brown, LM, Clegg, DJ. Central effects of estradiol in the regulation of food intake, body weight, and adiposity. J Steroid Biochem Mol Biol 2010;122:65–73. https://doi.org/10.1016/j.jsbmb.2009.12.005.Search in Google Scholar
28. Geary, N, Asarian, L. Cyclic estradiol treatment normalizes body weight and test meal size in ovariectomized rats. Physiol Behav 1999;67:141–7. https://doi.org/10.1016/s0031-9384(99)00060-8.Search in Google Scholar
29. Butera, PC. Estradiol and the control of food intake. Physiol Behav 2010;99:175–80. https://doi.org/10.1016/j.physbeh.2009.06.010.Search in Google Scholar
30. Poomthavorn, P, Khlairit, P, Mahachoklertwattana, P. Subcutaneous gonadotropin-releasing hormone agonist (triptorelin) test for diagnosing precocious puberty. Horm Res 2009;72:114–9. https://doi.org/10.1159/000232164.Search in Google Scholar
31. Department of Health, Ministry of Public Health. Reference for weight, height and nutritional indices in Thais aged 1 day to 19 years. Bangkok, Thailand: Department of Health, Ministry of Public Health; 2000.Search in Google Scholar
32. Marshall, WA, Tanner, JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291–303. https://doi.org/10.1136/adc.44.235.291.Search in Google Scholar
33. Greulich, WW, Pyle, SI. Radiographic atlas of skeletal development of the hand and wrist, 2nd ed. Standford, CA: Standford University Press; 1959.10.1097/00000441-195909000-00030Search in Google Scholar
34. WHO Growth reference data for 5-19 years. WHO reference 2007. Electronic citation. http://www.who.int/growthref/en/ [Accessed Dec 2018].Search in Google Scholar
35. Tascilar, ME, Bilir, P, Akinci, A, Kose, K, Akcora, D, Inceoglu, 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.Search in Google Scholar
36. Weber, DR, Moore, RH, Leonard, MB, Zemel, BS. Fat and lean BMI reference curves in children and adolescents and their utility in identifying excess adiposity compared with BMI and percentage body fat. Am J Clin Nutr 2013;98:49–56. https://doi.org/10.3945/ajcn.112.053611.Search in Google Scholar
37. Palmert, MR, Radovick, S, Boepple, PA. Leptin levels in children with central precocious puberty. J Clin Endocrinol Metab 1998;83:2260–5. https://doi.org/10.1210/jc.83.7.2260.Search in Google Scholar
38. Soni, AC, Conroy, MB, Mackey, RH, Kuller, LH. Ghrelin, leptin, adiponectin, and insulin levels and concurrent and future weight change in overweight, postmenopausal women. Menopause 2011;18:296–301. https://doi.org/10.1097/gme.0b013e3181f2e611.Search in Google Scholar
39. Karim, R, Stanczyk, FZ, Brinton, RD, Rettberg, J, Hodis, HN, Mack, WJ. Association of endogenous sex hormones with adipokines and ghrelin in postmenopausal women. J Clin Endocrinol Metab 2015;100:508–15. https://doi.org/10.1210/jc.2014-1839.Search in Google Scholar
40. Weickert, MO, Reimann, M, Otto, B, Hall, WL, Vafeiadou, K, Hallund, J, et al.. Soy isoflavones increase preprandial peptide YY (PYY), but have no effect on ghrelin and body weight in healthy postmenopausal women. J Negat Results Biomed 2006;14:5–11.10.1186/1477-5751-5-11Search in Google Scholar PubMed PubMed Central
41. Leeners, B, Geary, N, Tobler, PN, Asarian, L. Ovarian hormones and obesity. Hum Reprod Update 2017;23:300–21. https://doi.org/10.1093/humupd/dmw045.Search in Google Scholar
42. Ainslie, DA, Morris, MJ, Wittert, G, Turnbull, H, Proietto, J, Thorburn, AW. Estrogen deficiency causes central leptin insensitivity and increased hypothalamic neuropeptide Y. Int J Obes Relat Metab Disord 2001;25:1680–8. https://doi.org/10.1038/sj.ijo.0801806.Search in Google Scholar
© 2021 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Original Articles
- The utility of next-generation sequencing technologies in diagnosis of Mendelian mitochondrial diseases and reflections on clinical spectrum
- PATRO children, a multi-center, non-interventional study of the safety and effectiveness of Omnitrope® (somatropin) treatment in children: update on the United States cohort
- Effect of vitamin K2 and vitamin D3 on bone mineral density in children with acute lymphoblastic leukemia: a prospective cohort study
- Diagnostic utility of fine needle aspiration cytology in pediatric thyroid nodules based on Bethesda Classification
- Ultrasonographic determination of thyroid volume in infants and children from Aegean region of Turkey and comparison with national and international references
- Association of thyroid autoimmunity and the response to recombinant human growth hormone in Turner syndrome
- Evaluating transition in Turner syndrome in the West of Scotland
- Short-term effects of gonadotropin-releasing hormone analogue treatment on leptin, ghrelin and peptide YY in girls with central precocious puberty
- Metabolic syndrome and risk factors after hematopoietic stem cell transplantation in children and adolescents
- Urinary bisphenol A levels in prepubertal children with exogenous obesity according to presence of metabolic syndrome
- Associations of insulin-induced lipodystrophy in children, adolescents, and young adults with type 1 diabetes mellitus using recombinant human insulin: a cross-sectional study
- Incidence of diabetes in children and adolescents in Dhaka, Bangladesh
- Case Reports
- False-positive very long-chain fatty acids in a case of autoimmune adrenal insufficiency
- Prepubescent unilateral gynecomastia secondary to excessive soy consumption
- Detection of hepatocyte nuclear factor 4A(HNF4A) gene variant as the cause for congenital hyperinsulinism leads to revision of the diagnosis of the mother
- Coexistence of dyschondrosteosis associated to SHOX deficiency, pseudohypoparathyroidism 1B, and chronic autoimmune thyroiditis: a case report
Articles in the same Issue
- Frontmatter
- Original Articles
- The utility of next-generation sequencing technologies in diagnosis of Mendelian mitochondrial diseases and reflections on clinical spectrum
- PATRO children, a multi-center, non-interventional study of the safety and effectiveness of Omnitrope® (somatropin) treatment in children: update on the United States cohort
- Effect of vitamin K2 and vitamin D3 on bone mineral density in children with acute lymphoblastic leukemia: a prospective cohort study
- Diagnostic utility of fine needle aspiration cytology in pediatric thyroid nodules based on Bethesda Classification
- Ultrasonographic determination of thyroid volume in infants and children from Aegean region of Turkey and comparison with national and international references
- Association of thyroid autoimmunity and the response to recombinant human growth hormone in Turner syndrome
- Evaluating transition in Turner syndrome in the West of Scotland
- Short-term effects of gonadotropin-releasing hormone analogue treatment on leptin, ghrelin and peptide YY in girls with central precocious puberty
- Metabolic syndrome and risk factors after hematopoietic stem cell transplantation in children and adolescents
- Urinary bisphenol A levels in prepubertal children with exogenous obesity according to presence of metabolic syndrome
- Associations of insulin-induced lipodystrophy in children, adolescents, and young adults with type 1 diabetes mellitus using recombinant human insulin: a cross-sectional study
- Incidence of diabetes in children and adolescents in Dhaka, Bangladesh
- Case Reports
- False-positive very long-chain fatty acids in a case of autoimmune adrenal insufficiency
- Prepubescent unilateral gynecomastia secondary to excessive soy consumption
- Detection of hepatocyte nuclear factor 4A(HNF4A) gene variant as the cause for congenital hyperinsulinism leads to revision of the diagnosis of the mother
- Coexistence of dyschondrosteosis associated to SHOX deficiency, pseudohypoparathyroidism 1B, and chronic autoimmune thyroiditis: a case report
