{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T10:45:10Z","timestamp":1792320310447,"version":"4.4.0"},"reference-count":64,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>In recent decades, pubertal onset in girls has been considered to occur at an earlier age than previously. Exposure to endocrine-disrupting chemicals (EDCs) has been associated with alterations in pubertal timing, with several reports suggesting that EDCs may have a role in the secular trend in pubertal maturation, at least in girls. However, relevant studies give inconsistent results. On the other hand, the majority of girls with idiopathic precocious or early puberty present the growth pattern of constitutional advancement of growth (CAG), i.e., growth acceleration soon after birth. Herein, we show that the growth pattern of CAG is unrelated to exposure to endocrine-disrupting chemicals and is the major determinant of precocious or early puberty. Presented data suggest that EDCs, at most, have a minor effect on the timing of pubertal onset in girls.<\/jats:p>","DOI":"10.3390\/children8060492","type":"journal-article","created":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T03:48:08Z","timestamp":1623296888000},"page":"492","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Endocrine-Disrupting Chemicals and Early Puberty in Girls"],"prefix":"10.3390","volume":"8","author":[{"given":"Anastasios","family":"Papadimitriou","sequence":"first","affiliation":[{"name":"Pediatric Endocrinology Unit, Third Department of Pediatrics, National and Kapodistrian University of Athens, \u201cAttikon\u201d University Hospital, Haidari, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6083-3560","authenticated-orcid":false,"given":"Dimitrios","family":"Papadimitriou","sequence":"additional","affiliation":[{"name":"Pediatric\u2014Adolescent Endocrinology and Diabetes, Athens Medical Center, 15125 Marousi, Greece"},{"name":"Endocrine Unit, Aretaeion University Hospital, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1210\/er.2002-0019","article-title":"The timing of normal puberty and the age limits of sexual precocity: Variations around the world, secular trends, and changes after migration","volume":"24","author":"Parent","year":"2003","journal-title":"Endocr. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nature13545","article-title":"Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche","volume":"514","author":"Perry","year":"2014","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/nn.3319","article-title":"Epigenetic control of female puberty","volume":"16","author":"Lomniczi","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101260","DOI":"10.1016\/j.beem.2019.01.001","article-title":"IUGR: Genetic influences, metabolic problems, environmental associations\/triggers, current and future management","volume":"33","author":"Darendeliler","year":"2019","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1037\/bul0000270","article-title":"Biological aging in childhood and adolescence following experiences of threat and deprivation: A systematic review and meta-analysis","volume":"146","author":"Colich","year":"2020","journal-title":"Psychol. Bull."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Theodoropoulou, S., Papadopoulou, A., Karapanou, O., Priftis, K., Papaevangelou, V., and Papadimitriou, A. (2021). Study of Xbal and Pvull polymorphisms of estrogen receptor alpha (ER\u03b1) gene in girls with precocious\/early puberty. Endocrine.","DOI":"10.1007\/s12020-021-02695-0"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1542\/peds.99.4.505","article-title":"Secondary sexual characteristics and menses in young girls seen in office practice: A study from the Pediatric Research in Office Settings network","volume":"99","author":"Slora","year":"1997","journal-title":"Pediatrics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e2015665","DOI":"10.1001\/jamanetworkopen.2020.15665","article-title":"Trends in the Incidence of Central Precocious Puberty and Normal Variant Puberty Among Children in Denmark, 1998 to 2017","volume":"3","author":"Busch","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1093\/humrep\/16.5.1020","article-title":"Sexual precocity after immigration from developing countries to Belgium: Evidence of previous exposure to organochlorine pesticides","volume":"16","author":"Charlier","year":"2001","journal-title":"Hum. Reprod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4535","DOI":"10.1210\/jc.2010-0895","article-title":"Clinical review: Constitutional advancement of growth, a.k.a. early growth acceleration, predicts early puberty and childhood obesity","volume":"95","author":"Papadimitriou","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1210\/er.2009-0002","article-title":"Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement","volume":"30","author":"Bourguignon","year":"2009","journal-title":"Endocr. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4252","DOI":"10.1210\/endo.139.10.6216","article-title":"Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta","volume":"139","author":"Kuiper","year":"1998","journal-title":"Endocrinology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.envres.2008.08.007","article-title":"Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans","volume":"108","author":"Swan","year":"2008","journal-title":"Environ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.envint.2018.07.029","article-title":"Phthalate exposure and male reproductive outcomes: A systematic review of the human epidemiological evidence","volume":"121","author":"Radke","year":"2018","journal-title":"Environ. Int."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chebbi, M., Beltifa, A., Alibi, S., Di Bella, G., Loturco, V., Sire, O., Ben Mansour, H., and Le Tilly, V. (2020). Estrogenic hazards of short chain phthalates and bisphenols found in cosmetic products. Int. J. Environ. Health Res., 1\u201312.","DOI":"10.1080\/09603123.2020.1749573"},{"key":"ref_16","first-page":"895","article-title":"Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development","volume":"108","author":"Caro","year":"2000","journal-title":"Environ. Health Perspect."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/j.1365-2605.2012.01260.x","article-title":"High urinary phthalate concentration associated with delayed pubarche in girls","volume":"35","author":"Frederiksen","year":"2012","journal-title":"Int. J. Androl."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1093\/humrep\/deu081","article-title":"Phthalate exposure and pubertal development in a longitudinal study of US girls","volume":"29","author":"Wolff","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1515\/jpem-2017-0281","article-title":"Higher phthalate concentrations are associated with precocious puberty in normal weight Thai girls","volume":"30","author":"Srilanchakon","year":"2017","journal-title":"J. Pediatric Endocrinol. Metab. JPEM"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1039\/C9EM00512A","article-title":"Association of phthalate exposure with precocious and delayed pubertal timing in girls and boys: A systematic review and meta-analysis","volume":"22","author":"Golestanzadeh","year":"2020","journal-title":"Environ. Sci. Process. Impacts"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jpeds.2009.09.047","article-title":"Phthalate Exposure and Precocious Puberty in Females","volume":"156","author":"Lomenick","year":"2010","journal-title":"J. Pediatrics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.mce.2015.03.006","article-title":"Elevated phthalates' exposure in children with constitutional delay of growth and puberty","volume":"407","author":"Xie","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Jung, M.K., Choi, H.S., Suh, J., Kwon, A., Chae, H.W., Lee, W.J., Yoo, E.-G., and Kim, H.-S. (2019). The analysis of endocrine disruptors in patients with central precocious puberty. BMC Pediatrics, 19.","DOI":"10.1186\/s12887-019-1703-4"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/44517","article-title":"Exposure to bisphenol A advances puberty","volume":"401","author":"Howdeshell","year":"1999","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1093\/toxsci\/kfp266","article-title":"In utero and lactational exposure to bisphenol A, in contrast to ethinyl estradiol, does not alter sexually dimorphic behavior, puberty, fertility, and anatomy of female LE rats","volume":"114","author":"Ryan","year":"2010","journal-title":"Toxicol. Sci. Off. J. Soc. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1289\/ehp.0901690","article-title":"Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls","volume":"118","author":"Wolff","year":"2010","journal-title":"Environ. Health Perspect."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"16","DOI":"10.4274\/Jcrpe.1220","article-title":"Urinary bisphenol a levels in girls with idiopathic central precocious puberty","volume":"6","author":"Durmaz","year":"2014","journal-title":"J. Clin. Res. Pediatric Endocrinol."},{"key":"ref_28","first-page":"1233","article-title":"Increased levels of bisphenol A (BPA) in Thai girls with precocious puberty","volume":"29","author":"Supornsilchai","year":"2016","journal-title":"J. Pediatric Endocrinol. Metab. JPEM"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.envres.2014.08.010","article-title":"In utero and peripubertal exposure to phthalates and BPA in relation to female sexual maturation","volume":"134","author":"Watkins","year":"2014","journal-title":"Environ. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.1365-2605.2011.01244.x","article-title":"Early breast development in girls after prenatal exposure to non-persistent pesticides","volume":"35","author":"Andersen","year":"2012","journal-title":"Int. J. Androl."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1093\/humrep\/deh292","article-title":"In utero exposure to organochlorines and age at menarche","volume":"19","author":"Vasiliu","year":"2004","journal-title":"Hum. Reprod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e127","DOI":"10.1542\/peds.2004-1161","article-title":"Relationship of lead, mercury, mirex, dichlorodiphenyldichloroethylene, hexachlorobenzene, and polychlorinated biphenyls to timing of menarche among Akwesasne Mohawk girls","volume":"115","author":"Denham","year":"2005","journal-title":"Pediatrics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.envres.2008.03.006","article-title":"Environmental exposures and puberty in inner-city girls","volume":"107","author":"Wolff","year":"2008","journal-title":"Environ. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1289\/ehp.7287","article-title":"Prenatal DDT exposure in relation to anthropometric and pubertal measures in adolescent males","volume":"112","author":"Gladen","year":"2004","journal-title":"Environ. Health Perspect."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1289\/ehp.1408778","article-title":"Brominated flame retardants and other persistent organohalogenated compounds in relation to timing of puberty in a longitudinal study of girls","volume":"123","author":"Windham","year":"2015","journal-title":"Environ. Health Perspect."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.envint.2017.01.003","article-title":"Association of prenatal and childhood PBDE exposure with timing of puberty in boys and girls","volume":"100","author":"Harley","year":"2017","journal-title":"Environ. Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1515\/jpem-2015-0116","article-title":"Pilot study on the dietary habits and lifestyles of girls with idiopathic precocious puberty from the city of Rome: Potential impact of exposure to flame retardant polybrominated diphenyl ethers","volume":"28","author":"Tassinari","year":"2015","journal-title":"J. Pediatric Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1111\/j.1365-2605.2005.00561.x","article-title":"Endocrine disrupters and human puberty","volume":"29","author":"Schoeters","year":"2006","journal-title":"Int. J. Androl."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jpeds.2006.02.005","article-title":"Early growth acceleration in girls with idiopathic precocious puberty","volume":"149","author":"Papadimitriou","year":"2006","journal-title":"J. Pediatr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1159\/000330005","article-title":"Constitutional advancement of growth is associated with early puberty in girls","volume":"76","author":"Papadimitriou","year":"2011","journal-title":"Horm. Res. Paediatr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.jnutbio.2015.09.008","article-title":"Mono-2-ethylhexyl phthalate (MEHP) alters histiotrophic nutrition pathways and epigenetic processes in the developing conceptus","volume":"27","author":"Sant","year":"2016","journal-title":"J. Nutr. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.envpol.2013.03.023","article-title":"Associations of prenatal exposure to phenols with birth outcomes","volume":"178","author":"Tang","year":"2013","journal-title":"Environ. Pollut."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.taap.2013.01.020","article-title":"Mono-2-ethylhexyl phthalate induces oxidative stress responses in human placental cells in vitro","volume":"268","author":"Tetz","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1289\/ehp.11007","article-title":"Prenatal phenol and phthalate exposures and birth outcomes","volume":"116","author":"Wolff","year":"2008","journal-title":"Environ. Health Perspect."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S65","DOI":"10.1097\/01.ede.0000276629.94631.94","article-title":"Prenatal phthalate and phenol exposures in relation to birth outcomes in a NYC birth cohort","volume":"18","author":"Wolff","year":"2007","journal-title":"Epidemiology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5422","DOI":"10.1038\/s41598-019-41134-z","article-title":"Early pregnancy exposure to endocrine disrupting chemical mixtures are associated with inflammatory changes in maternal and neonatal circulation","volume":"9","author":"Kelley","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"79","DOI":"10.4103\/jrms.JRMS_919_19","article-title":"The association between maternal exposure to organophosphate pesticides and neonatal anthropometric measures: A systematic review and meta-analysis","volume":"25","author":"Khoshhali","year":"2020","journal-title":"J. Res. Med. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.envint.2016.06.013","article-title":"Urinary phthalate metabolite and bisphenol A associations with ultrasound and delivery indices of fetal growth","volume":"94","author":"Ferguson","year":"2016","journal-title":"Environ. Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.envres.2015.06.023","article-title":"Perinatal exposure to chlordecone and infant growth","volume":"142","author":"Costet","year":"2015","journal-title":"Environ. Res."},{"key":"ref_50","unstructured":"Cameron, N., and Bogin, B. (2012). Human Growth and Development, Academic Press. [2nd ed.]."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1203\/00006450-199508000-00022","article-title":"Children born small for gestational age: Do they catch up?","volume":"38","author":"Lemmen","year":"1995","journal-title":"Pediatric Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1210\/jcem-68-1-232","article-title":"Functional hypersomatotropism in small for gestational age (SGA) newborn infants","volume":"68","author":"Deiber","year":"1989","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_53","first-page":"2021","article-title":"Small as fetus and short as child: From endogenous to exogenous growth hormone1","volume":"82","author":"Zegher","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1046\/j.1365-3016.2003.00494.x","article-title":"Growth velocity during the first postnatal week of life is linked to a spurt of IGF-I effect","volume":"17","author":"Skalkidou","year":"2003","journal-title":"Paediatr. Perinat. Epidemiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/ijpo.12053","article-title":"The sequence of prenatal growth restraint and post-natal catch-up growth leads to a thicker intima-media and more pre-peritoneal and hepatic fat by age 3\u20136 years","volume":"11","author":"Sebastiani","year":"2016","journal-title":"Pediatric Obes."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3109\/14767058.2013.832870","article-title":"SGA children: Auxological and metabolic outcomes\u2014The role of GH treatment","volume":"26","author":"Saggese","year":"2013","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Deng, H.Z., Deng, H., Cen, C.Q., Chen, K.Y., and Du, M.L. (2014). Post-receptor crosstalk between growth hormone and insulin signal in rats born small for gestational age with catch-up growth. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100459"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"E786","DOI":"10.1210\/jc.2011-3261","article-title":"Higher levels of IGF-I and adrenal androgens at age 8 years are associated with earlier age at menarche in girls","volume":"97","author":"Thankamony","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.tem.2005.11.006","article-title":"Evolution, development and timing of puberty","volume":"17","author":"Gluckman","year":"2006","journal-title":"Trends Endocrinol. Metab TEM"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.jpag.2015.12.002","article-title":"The Evolution of the Age at Menarche from Prehistorical to Modern Times","volume":"29","author":"Papadimitriou","year":"2016","journal-title":"J. Pediatric Adolesc. Gynecol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/nrendo.2015.163","article-title":"Endocrine disruptors and obesity","volume":"11","author":"Heindel","year":"2015","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1210\/jc.2015-1841","article-title":"DDT Exposure in utero and breast cancer","volume":"100","author":"Cohn","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1097\/MED.0b013e32830ce95c","article-title":"Putative environmental-endocrine disruptors and obesity: A review","volume":"15","author":"Elobeid","year":"2008","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/S2352-4642(18)30306-7","article-title":"Is there a causal relationship between obesity and puberty?","volume":"3","author":"Reinehr","year":"2019","journal-title":"Lancet Child Adolesc. Health"}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/8\/6\/492\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:12:43Z","timestamp":1760163163000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/8\/6\/492"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,10]]},"references-count":64,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["children8060492"],"URL":"https:\/\/doi.org\/10.3390\/children8060492","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,10]]}}}