Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Mericq, Veronica / Toppari, Jorma

IMPACT FACTOR 2018: 1.239

CiteScore 2018: 1.22

SCImago Journal Rank (SJR) 2018: 0.507
Source Normalized Impact per Paper (SNIP) 2018: 0.562

See all formats and pricing
More options …
Volume 29, Issue 3


The relation of urinary bisphenol A with kisspeptin in girls diagnosed with central precocious puberty and premature thelarche

İlker Tolga Özgen
  • Division of Pediatric Endocrinology, Bezmialem Vakif University Medical Faculty, Department of Pediatrics, Istanbul, Turkey
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Emel Torun
  • Corresponding author
  • Division of Pediatric Endocrinology, Bezmialem Vakif University Medical Faculty, Department of Pediatrics, Istanbul, Turkey
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Bilge Bayraktar-Tanyeri / Erdem Durmaz
  • Division of Pediatric Endocrinology, Isifa University Bornova Health and Department of Pediatrics, Izmir, Turkey
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Elif Kılıç
  • Bezmialem Vakif University Medical Faculty, Department of Clinical Biochemistry, Istanbul, Turkey
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Yaşar Cesur
  • Division of Pediatric Endocrinology, Bezmialem Vakif University Medical Faculty, Department of Pediatrics, Istanbul, Turkey
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2015-11-13 | DOI: https://doi.org/10.1515/jpem-2015-0235


Background: Bisphenol A (BPA) is known as an endocrine disruptor and it is supposed to have a role on the development of central precocious puberty (CPP). Kisspeptin, a hypothalamic peptide, is a neuromodulator of gonadotropin releasing hormone and it has an important role on regulation of the onset of puberty. The BPA levels in girls with CPP and premature thelarche (PT) and its relation with kisspeptin levels were investigated.

Methods: Twenty-eight girls with CPP, 28 girls with PT and 22 prepubertal girls as a control group were enrolled to the study. Urinary BPA and serum kisspeptin levels were compared in the groups. Bivariate correlations were performed to evaluate the relations of BPA with kisspeptin and estradiol.

Results: There was no statistical difference between groups regarding BPA levels. Serum kisspeptin levels were higher in CPP group than controls [306.56 (interquartile range (IQR), 175.63–504.66) vs. 157.62 (IQR, 55.61–285.00) p: 0.008]. There were no correlations between BPA and kisspeptin levels (r: 0.088, p: 0.391) and between BPA and estradiol (r: –0.171, p: 0.144).

Conclusions: The BPA levels did not differentiate between groups and it seems that the exposed amount of BPA in daily life did not affect kisspeptin levels in girls with CPP and PT.

Keywords: bisphenol A; kisspeptin; precocious puberty; premature thelarche


  • 1.

    Ma HM, Du ML, Luo XP, Chen SK, Liu L, et al. Onset of breast and pubic hair development and menses in urban chinese girls. Pediatrics 2009;124:269–77.Web of ScienceCrossrefGoogle Scholar

  • 2.

    Aksglaede L, Sørensen K, Petersen JH, Skakkebaek NE, Juul A, et al. Recent decline in age at breast development: the Copenhagen Puberty Study. Pediatrics 2009;123:932–9.CrossrefWeb of ScienceGoogle Scholar

  • 3.

    Curfman AL, Reljanovic SM, McNelis KM, Dong TT, Lewis SA, et al. Premature thelarche in infants and toddlers: prevalence, natural history and environmental determinants. J Pediatr Adolesc Gynecol 2011;24:338–41.Web of ScienceCrossrefGoogle Scholar

  • 4.

    Yang O, Kim HL, Weon JI, Seo YR. Endocrine-disrupting Chemicals: review of toxicological mechanisms using molecular pathway analysis. J Cancer Prev 2015;20:12–24.CrossrefGoogle Scholar

  • 5.

    Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, et al. Endocrine-disrupting chemicals: an endocrine society scientific statement. Endocr Rev 2009;30:293–342.Web of ScienceCrossrefGoogle Scholar

  • 6.

    Careghini A, Mastorgio AF, Saponaro S, Sezenna E. Bisphenol A, nonylphenols, benzophenones, and benzotriazoles in soils, groundwater, surface water, sediments, and food: a review. Environ Sci Pollut Res Int 2015;22:5711–41.Web of ScienceCrossrefGoogle Scholar

  • 7.

    Terasawa E, Fernandez DL. Neurobiological mechanisms of the onset of puberty in primates. Endocr Rev 2001;22:111–51.Google Scholar

  • 8.

    Hrabovszky E, Steinhauser A, Barabas K, Shughrue PJ, Petersen SL, et al. Estrogen receptor-beta immunoreactivity in luteinizing hormone-releasing hormone neurones of the rat brain. Endocrinology 2001;142:3261–4.Google Scholar

  • 9.

    Krege JH, Hodgin JB, Couse JF, Enmark E, Warner M, et al. Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Proc Natl Acad Sci 1998;95:15677–82.CrossrefGoogle Scholar

  • 10.

    Millar RP, Babwah AV. KISS1R: Hallmarks of an Effective Regulator of the Neuroendocrine Axis. Neuroendocrinology 2015;101:193–210.CrossrefWeb of ScienceGoogle Scholar

  • 11.

    Seminara SB. Mechanisms of disease: the first kiss – a crucial role for kisspeptin-1 and its receptor, G-protein-coupled receptor 54, in puberty and reproduction. Nat Clin Pract Endocrinol Metab 2006;2:328–34.CrossrefGoogle Scholar

  • 12.

    Lee HS, Park EJ, Oh JH, Moon G, Hwang MS, et al. Bisphenol A exerts estrogenic effects by modulating CDK1/2 and p38 MAP kinase activity. Biosci Biotechnol Biochem 2014;78:1371–5.Web of ScienceGoogle Scholar

  • 13.

    Greulich WW, Pyle SI. Radiographic atlas of skeletal development of the hand and wrist, 2nd ed. Stanford, CA: Stanford University Press, 1959:1–255.Google Scholar

  • 14.

    Cole TJ. The LMS method for constructing normalized growth standards. Eur J Clin Nutr 1990;44:45–60.Google Scholar

  • 15.

    Tanner JM. Growth and maturation during adolescence. Nutr Rev 1981;39:43–55.CrossrefGoogle Scholar

  • 16.

    Battal D, Cok I, Unlusayin I, Tunctan B. Development and validation of an LC-MS/MS method for simultaneous quantitative analysis of free and conjugated bisphenol A in human urine. Biomed Chromatogr 2014;28:686–93.CrossrefGoogle Scholar

  • 17.

    Kendig EL, Buesing DR, Christie SM, Cookman CJ, Gear RB, et al. Estrogen-like disruptive effects of dietary exposure to bisphenol A or 17α-ethinyl estradiol in CD1 mice. Int J Toxicol 2012;31:537–50.Web of ScienceCrossrefGoogle Scholar

  • 18.

    Li Y, Zhang W, Liu J, Wang W, Li H, et al. Prepubertal bisphenol A exposure interferes with ovarian follicle development and its relevant gene expression. Reprod Toxicol 2014;44:33–40.CrossrefWeb of ScienceGoogle Scholar

  • 19.

    McGuinn LA, Ghazarian AA, Joseph Su L, Ellison GL. Urinary bisphenol A and age at menarche among adolescent girls: evidence from NHANES 2003-2010. Environ Res 2015;136:381–6.Web of ScienceGoogle Scholar

  • 20.

    Mueller JK, Heger S. Endocrine disrupting chemicals affect the gonadotropin releasing hormone neuronal network. Reprod Toxicol 2014;44:73–84.CrossrefGoogle Scholar

  • 21.

    Ceccarelli I, Della Seta D, Fiorenzani P, Farabollini F, Aloisi AM. Estrogenic chemicals at puberty change ERalpha in the hypothalamus of male and female rats. Neurotoxicol Teratol 2007;29:108–15.CrossrefWeb of ScienceGoogle Scholar

  • 22.

    Nah WH, Park MJ, Gye MC. Effects of early prepubertal exposure to bisphenol A on the onset of puberty, ovarian weights, and estrous cycle in female mice. Clin Exp Reprod Med 2011;38: 75–81.CrossrefGoogle Scholar

  • 23.

    Durmaz E, Aşçı A, Erkekoğlu P, Akçurin S, Gümüşel BK, et al. Urinary bisphenol a levels in girls with idiopathic central precocious puberty. J Clin Res Pediatr Endocrinol 2014;6:16–21.CrossrefWeb of ScienceGoogle Scholar

  • 24.

    Qiao L, Zheng L, Cai D. Study on the levels of the bisphenol A, octylphenol, 4-nonylphenol in serum of precocious girls. Wei Sheng Yan Jiu 2010;39:9–12.Google Scholar

  • 25.

    Yum T, Lee S, Kim Y. Association between precocious puberty and some endocrine disruptors in human plasma. J Environ Sci Health A Tox Hazard Subst Environ Eng 2013;48:912–7.CrossrefGoogle Scholar

  • 26.

    Topaloglu AK, Tello JA, Kotan LD, Ozbek MN, Yilmaz MB, et al. Inactivating KISS1 mutation and hypogonadotropic hypogonadism. N Engl J Med 2012;366:629–35.Google Scholar

  • 27.

    Teles MG, Bianco SD, Brito VN, Trarbach EB, Kuohung W, et al. A GPR54-activating mutation in a patient with central precocious puberty. N Engl J Med 2008;358:709–15.Google Scholar

  • 28.

    Silveira LG, Noel SD, Silveira-Neto AP, Abreu AP, Brito VN, et al. Mutations of the KISS1 gene in disorders of puberty. J Clin Endocrinol Metab 2010;95:2276–80.Web of ScienceGoogle Scholar

  • 29.

    Bianco SD, Vandepas L, Correa-Medina M, Gereben B, Mukherjee A, et al. KISS1R intracellular trafficking and degradation: effect of the Arg386Pro disease-associated mutation. Endocrinology 2011;152:1616–26.Web of ScienceGoogle Scholar

  • 30.

    Abacı A, Çatlı G, Anık A, Küme T, Çalan ÖG, et al. Significance of serum neurokinin B and kisspeptin levels in the differential diagnosis of premature thelarche and idiopathic central precocious puberty. Peptides 2015;64:29–33.CrossrefWeb of ScienceGoogle Scholar

  • 31.

    Wang X, Chang F, Bai Y, Chen F, Zhang J, et al. Bisphenol A enhances kisspeptin neurons in anteroventral periventricular nucleus of female mice. J Endocrinol 2014;221:201–13.Web of ScienceCrossrefGoogle Scholar

  • 32.

    Kurian JR, Keen KL, Kenealy BP, Garcia JP, Hedman CJ, et al. Acute influences of Bisphenol A exposure on hypothalamic release of gonadotropin releasing hormone and kisspeptin in female rhesus monkeys. Endocrinology 2015;156:2563–70.CrossrefWeb of ScienceGoogle Scholar

  • 33.

    Lee CT, Tung YC, Tsai WY. Premature thelarche in Taiwanese girls. J Pediatr Endocrinol Metab 2010;23:879–84.Web of ScienceCrossrefGoogle Scholar

  • 34.

    de Vries L, Guz-Mark A, Lazar L, Reches A, Phillip M. Premature thelarche: age at presentation affects clinical course but not clinical characteristics or risk to progress to precocious puberty. J Pediatr 2010;156:466–71.CrossrefGoogle Scholar

  • 35.

    Berberoğlu M. Precocious puberty and normal variant puberty: definition, etiology, diagnosis and current management. J Clin Res Pediatr Endocrinol 2009;1:164–74.Google Scholar

  • 36.

    Akinci A, Cetin D, Ilhan N. Plasma kisspeptin levels in girls with premature thelarche. J Clin Res Pediatr Endocrinol 2012;4:61–5.CrossrefGoogle Scholar

  • 37.

    Atay Z, Turan S, Guran T, Furman A, Bereket A. The prevalence and risk factors of premature thelarche and pubarche in 4- to 8-year-old girls. Acta Paediatr 2012;101:71–5.CrossrefWeb of ScienceGoogle Scholar

  • 38.

    White AM, Singh R, Rais T, Coffey BJ. Premature thelarche in an 8-year-old girl following prolonged use of risperidone. J Child Adolesc Psychopharmacol 2014;24:228–30.Web of ScienceCrossrefGoogle Scholar

  • 39.

    Dundar B, Pirgon O, Sangun O, Doguc DK. Elevated leptin levels in nonobese girls with premature thelarche. J Invest Med 2013;61:984–8.Google Scholar

  • 40.

    Paris F, Gaspari L, Servant N, Philibert P, Sultan C. Increased serum estrogenic bioactivity in girls with premature thelarche: a marker of environmental pollutant exposure? Gynecol Endocrinol 2013;29:788–92.Web of ScienceCrossrefGoogle Scholar

  • 41.

    Fortes EM, Malerba MI, Luchini PD, Sugawara EK, Sumodjo L, et al. High intake of phytoestrogens and precocious thelarche: case report with a possible correlation. Arq Bras Endocrinol Metabol 2007;51:500–3.CrossrefWeb of ScienceGoogle Scholar

  • 42.

    Chen LH, Shi JR, Fang YL, Liang L, Chen WQ, et al. Serum bisphenol A concentration and premature thelarche in female infants aged 4-month to 2-year. Indian J Pediatr 2015;82:221–4.Web of ScienceGoogle Scholar

About the article

Corresponding author: Emel Torun, Division of Pediatric Endocrinology, Bezmialem Vakif University Medical Faculty, Department of Pediatrics, Vatan Street, Fatih, Istanbul, Turkey, Mobile: +905324652836, E-mail:

Received: 2015-06-12

Accepted: 2015-09-30

Published Online: 2015-11-13

Published in Print: 2016-03-01

Citation Information: Journal of Pediatric Endocrinology and Metabolism, Volume 29, Issue 3, Pages 337–341, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2015-0235.

Export Citation

©2016 by De Gruyter.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Yao Chen, Yingcan Wang, Guodong Ding, Ying Tian, Zhijun Zhou, Xiumin Wang, Lixiao Shen, and Hong Huang
Environment International, 2018
Alberto Leonardi, Marta Cofini, Donato Rigante, Laura Lucchetti, Clelia Cipolla, Laura Penta, and Susanna Esposito
International Journal of Environmental Research and Public Health, 2017, Volume 14, Number 9, Page 1044

Comments (0)

Please log in or register to comment.
Log in