Background/Aims: Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants and have shown endocrine disruption properties in experimental studies. The aim of this study was to investigate the association between the exposure to PBDEs and alterations of puberty in girls referred for idiopathic central precocious puberty (ICPP) and premature thelarche (PT). Methods: A case-control study was conducted in 124 girls: 37 girls with ICPP (mean age 7.4 ± 0.9 years), 56 with PT (mean age 5.7 ± 2.1 years) and 31 controls (mean age 5.4 ± 1.9 years). PBDE serum concentrations, hormone levels and anthropometry were assessed. PBDE concentrations were corrected for total serum lipid content. Individual exposure to PBDEs was evaluated through ad hoc questionnaires. Results: PBDE serum concentrations corrected for total lipid content were significantly higher in girls with PT (mean 1.49 ± 0.63 log ng/g) than in controls (mean 1.23 ± 0.54 log ng/g; p < 0.05). PT girls showed higher levels of PBDE than ICPP girls (1.49 ± 0.63 vs. 1.37 ± 0.49 log ng/g), though this was not significant. An analysis of the questionnaires revealed no significant differences in exposure between the three groups. Conclusion: Our findings suggest that higher concentrations of serum PBDEs are associated with PT in girls.

1.
Besis A, Samara C: Polybrominated diphenyl ethers (PBDEs) in the indoor and outdoor environments - a review on occurrence and human exposure. Environ Pollut 2012;169:217-229.
2.
Frederiksen M, Vorkamp K, Thomsen M, Knudsen LE: Human internal and external exposure to PBDEs - a review of levels and sources. Int J Hyg Environ Health 2009;212:109-134.
3.
Schecter A, Colacino J, Haffner D, Patel K, Opel M, Päpke O, Birnbaum L: Perfluorinated compounds, polychlorinated biphenyls, and organochlorine pesticide contamination in composite food samples from Dallas, Texas, USA. Environ Health Perspect 2010;118:796-802.
4.
Sjödin A, Jones RS, Focant JF, Lapeza C, Wang RY, McGahee EE, Zhang Y, Turner WE, Slazyk B, Needham LL, Patterson DG: Retrospective time-trend study of polybrominated diphenyl ether and polybrominated and polychlorinated biphenyl levels in human serum from the United States. Environ Health Perspect 2004;112:654-658.
5.
Wu XM, Bennett DH, Moran RE, Sjödin A, Jones RS, Tancredi DJ, Tulve NS, Clifton MS, Colón M, Weathers W, Hertz-Picciotto I: Polybrominated diphenyl ether serum concentrations in a Californian population of children, their parents, and older adults: an exposure assessment study. Environ Health 2015;14:23.
6.
Mazdai A, Dodder NG, Abernathy MP, Hites RA, Bigsby RM: Polybrominated diphenyl ethers in maternal and fetal blood samples. Environ Health Perspect 2003;111:1249-1252.
7.
Lorber M: Exposure of Americans to polybrominated diphenyl ethers. J Expo Sci Environ Epidemiol 2008;18:2-19.
8.
Hamers T, Kamstra JH, Sonneveld E, Murk AJ, Kester MH, Andersson PL, Legler J, Brouwer A: In vitro profiling of the endocrine-disrupting potency of brominated flame retardants. Toxicol Sci 2006;92:157-173.
9.
Hamers T, Kamstra JH, Sonneveld E, Murk AJ, Visser TJ, Van Velzen MJ, Brouwer A, Bergman A: Biotransformation of brominated flame retardants into potentially endocrine-disrupting metabolites, with special attention to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47). Mol Nutr Food Res 2008;52:284-298.
10.
Kester MH, Bulduk S, van Toor H, Tibboel D, Meinl W, Glatt H, Falany CN, Coughtrie MW, Schuur AG, Brouwer A, Visser TJ: Potent inhibition of estrogen sulfotransferase by hydroxylated metabolites of polyhalogenated aromatic hydrocarbons reveals alternative mechanism for estrogenic activity of endocrine disrupters. J Clin Endocrinol Metab 2002;87:1142-1150.
11.
Kojima H, Takeuchi S, Uramaru N, Sugihara K, Yoshida T, Kitamura S: Nuclear hormone receptor activity of polybrominated diphenyl ethers and their hydroxylated and methoxylated metabolites in transactivation assays using Chinese hamster ovary cells. Environ Health Perspect 2009;117:1210-1218.
12.
Kuriyama SN, Talsness CE, Grote K, Chahoud I: Developmental exposure to low dose PBDE 99: effects on male fertility and neurobehavior in rat offspring. Environ Health Perspect 2005;113:149-154.
13.
Lilienthal H, Hack A, Roth-Härer A, Grande SW, Talsness CE: Effects of developmental exposure to 2,2,4,4,5-pentabromodiphenyl ether (PBDE-99) on sex steroids, sexual development, and sexually dimorphic behavior in rats. Environ Health Perspect 2006;114:194-201.
14.
Talsness CE, Kuriyama SN, Sterner-Kock A, Schnitker P, Grande SW, Shakibaei M, Andrade A, Grote K, Chahoud I: In utero and lactational exposures to low doses of polybrominated diphenyl ether-47 alter the reproductive system and thyroid gland of female rat offspring. Environ Health Perspect 2008;116:308-314.
15.
Maranghi F, Tassinari R, Moracci G, Altieri I, Rasinger JD, Carroll TS, Hogstrand C, Lundebye AK, Mantovani A: Dietary exposure of juvenile female mice to polyhalogenated seafood contaminants (HBCD, BDE-47, PCB-153, TCDD): comparative assessment of effects in potential target tissues. Food Chem Toxicol 2013;56:443-449.
16.
Blanck HM, Marcus M, Tolbert PE, Rubin C, Henderson AK, Hertzberg VS, Zhang RH, Cameron L: Age at menarche and Tanner stage in girls exposed in utero and postnatally to polybrominated biphenyl. Epidemiology 2000;11:641-647.
17.
Vasiliu O, Muttineni J, Karmaus W: In utero exposure to organochlorines and age at menarche. Hum Reprod 2004;19:1506-1512.
18.
Chao HR, Wang SL, Lee WJ, Wang YF, Päpke O: Levels of polybrominated diphenyl ethers (PBDEs) in breast milk from central Taiwan and their relation to infant birth outcome and maternal menstruation effects. Environ Int 2007;33:239-245.
19.
Chao HR, Shy CG, Wang SL, Chen SC, Koh TW, Chen FA, Chang-Chien GP, Tsou TC: Impact of non-occupational exposure to polybrominated diphenyl ethers on menstruation characteristics of reproductive-age females. Environ Int 2010;36:728-735.
20.
Harley KG, Marks AR, Chevrier J, Bradman A, Sjödin A, Eskenazi B: PBDE concentrations in women's serum and fecundability. Environ Health Perspect 2010;118:699-704.
21.
Chen A, Chung E, DeFranco EA, Pinney SM, Dietrich KN: Serum PBDEs and age at menarche in adolescent girls: analysis of the National Health and Nutrition Examination Survey 2003-2004. Environ Res 2011;111:831-837.
22.
Marshall WA, Tanner JM: Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291-303.
23.
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:e752-e762.
24.
Chemaitilly W, Trivin C, Adan L, Gall V, Sainte-Rose C, Brauner R: Central precocious puberty: clinical and laboratory features. Clin Endocrinol (Oxf) 2001;54:289-294.
25.
Pedicelli S, Alessio P, Scirè G, Cappa M, Cianfarani S: Routine screening by brain magnetic resonance imaging is not indicated in every girl with onset of puberty between the ages of 6 and 8 years. J Clin Endocrinol Metab 2014;99:4455-4461.
26.
Herman-Giddens ME, Slora EJ, Wasserman RC, Bourdony CJ, Bhapkar MV, Koch GG, Hasemeier CM: Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings Network. Pediatrics 1997;99:505-512.
27.
Bizzarri C, Spadoni GL, Bottaro G, Montanari G, Giannone G, Cappa M, Cianfarani S: The response to gonadotropin releasing hormone (GnRH) stimulation test does not predict the progression to true precocious puberty in girls with onset of premature thelarche in the first three years of life. J Clin Endocrinol Metab 2014;99:433-439.
28.
Van Winter JT, Noller KL, Zimmerman D, Melton LJ: Natural history of premature thelarche in Olmsted County, Minnesota, 1940 to 1984. J Pediatr 1990;116:278-280.
29.
Neely EK, Hintz RL, Wilson DM, Lee PA, Gautier T, Argente J, Stene M: Normal ranges for immunochemiluminometric gonadotropin assays. J Pediatr 1995;127:40-46.
30.
Cacciari E, Milani S, Balsamo A, Spada E, Bona G, Cavallo L, Cerutti F, Gargantini L, Greggio N, Tonini G, Cicognani A: Italian cross-sectional growth charts for height, weight and BMI (2 to 20 years). J Endocrinol Invest 2006;29:581-593.
31.
Tanner JM, Whitehouse RH: Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 1976;51:170-179.
32.
Carel JC, Léger J: Clinical practice. Precocious puberty. N Engl J Med 2008;358:2366-2377.
33.
Buck Louis GM, Gray LE, Marcus M, Ojeda SR, Pescovitz OH, Witchel SF, Sippell W, Abbott DH, Soto A, Tyl RW, Bourguignon JP, Skakkebaek NE, Swan SH, Golub MS, Wabitsch M, Toppari J, Euling SY: Environmental factors and puberty timing: expert panel research needs. Pediatrics 2008;121(suppl 3):S192-S207.
34.
Ilicki A, Prager Lewin R, Kauli R, Kaufman H, Schachter A, Laron Z: Premature thelarche - natural history and sex hormone secretion in 68 girls. Acta Paediatr Scand 1984;73:756-762.
35.
Wang C, Zhong CQ, Leung A, Low LC: Serum bioactive follicle-stimulating hormone levels in girls with precocious sexual development. J Clin Endocrinol Metab 1990;70:615-619.
36.
Rosenfield RL: Normal and almost normal precocious variations in pubertal development premature pubarche and premature thelarche revisited. Horm Res 1994;41(suppl 2):7-13.
37.
Stanhope R, Abdulwahid NA, Adams J, Brook CG: Studies of gonadotrophin pulsatility and pelvic ultrasound examinations distinguish between isolated premature thelarche and central precocious puberty. Eur J Pediatr 1986;145:190-194.
38.
Dumic M, Tajic M, Mardesic D, Kalafatic Z: Premature thelarche: a possible adrenal disorder. Arch Dis Child 1982;57:200-203.
39.
Sáenz de Rodríguez CA, Bongiovanni AM, Conde de Borrego L: An epidemic of precocious development in Puerto Rican children. J Pediatr 1985;107:393-396.
40.
Pasquino AM, Tebaldi L, Cioschi L, Cives C, Finocchi G, Maciocci M, Mancuso G, Boscherini B: Premature thelarche: a follow up study of 40 girls. Natural history and endocrine findings. Arch Dis Child 1985;60:1180-1182.
41.
Ma HM, Du ML, Luo XP, Chen SK, Liu L, Chen RM, Zhu C, Xiong F, Li T, Wang W, Liu GL; Pubertal Study Group of the Society of Pediatric Endocrinology and Genetic Disease, Chinese Medical Association: Onset of breast and pubic hair development and menses in urban Chinese girls. Pediatrics 2009;124: e269-e277.
42.
Aksglaede L, Sørensen K, Petersen JH, Skakkebaek NE, Juul A: Recent decline in age at breast development: The Copenhagen Puberty Study. Pediatrics 2009;123:e932-e939.
43.
Mouritsen A, Aksglaede L, Sørensen K, Mogensen SS, Leffers H, Main KM, Frederiksen H, Andersson AM, Skakkebaek NE, Juul A: Hypothesis: exposure to endocrine-disrupting chemicals may interfere with timing of puberty. Int J Androl 2010;33:346-359.
44.
Euling SY, Selevan SG, Pescovitz OH, Skakkebaek NE: Role of environmental factors in the timing of puberty. Pediatrics 2008;121(suppl 3):S167-S171.
45.
Larriuz-Serrano MC, Pérez-Cardona CM, Ramos-Valencia G, Bourdony CJ: Natural history and incidence of premature thelarche in Puerto Rican girls aged 6 months to 8 years diagnosed between 1990 and 1995. PR Health Sci J 2001;20:13-18.
46.
Scaglioni S, Di Pietro C, Bigatello A, Chiumello G: Breast enlargement at an Italian school. Lancet 1978;1:551-552.
47.
Meerts IA, Letcher RJ, Hoving S, Marsh G, Bergman A, Lemmen JG, van der Burg B, Brouwer A: In vitro estrogenicity of polybrominated diphenyl ethers, hydroxylated PDBEs, and polybrominated bisphenol a compounds. Environ Health Perspect 2001;109:399-407.
48.
Mercado-Feliciano M, Bigsby RM: Hydroxylated metabolites of the polybrominated diphenyl ether mixture DE-71 are weak estrogen receptor-α ligands. Environ Health Perspect 2008;116:1315-1321.
49.
Mercado-Feliciano M, Bigsby RM: The polybrominated diphenyl ether mixture DE-71 is mildly estrogenic. Environ Health Perspect 2008;116:605-611.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.