title: Could exposure to phthalates speed up or delay pubertal onset and development? A 1.5-year follow-up of a school-based population.
abstract: OBJECTIVE
  Phthalates may interfere with the timing of pubertal development in adolescence and existing studies have shown inconsistent results. This study aims to assess the associations of pubertal onset and progression with urinary concentrations of phthalate metabolites in school-aged boys and girls.
  
  
  METHODS
  Using isotope-dilution liquid chromatography tandem mass spectrometry, we analyzed 6 phthalate metabolites in urine samples of 430 children (222 boys and 208 girls) aged 9.7 ± 2.2 years (age range 6.1 to 13.8 years) at baseline and 18 months of follow-up. The associations of exposures to phthalates with pubertal development such as the testis, breast and pubic hair were evaluated using ordered logistic regression models, adjusting for baseline development stage, current chronological age, current body fat composition, and parental education.
  
  
  RESULTS
  Urinary mono-n-butyl phthalate (MnBP) was associated with a 39% increase in the odds of presenting lower pubic hair development stages in boys, and mono (2-ethylhexyl) phthalate (MEHP) (p < 0.10), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) were associated with 54%-65% increase in the odds of presenting higher breast development stages in girls (p < 0.05), while MEHHP and MEOHP were also associated with a 70% increase in the odds of menarche onset (p < 0.05). After adjusting for potential confounding variables, the associations of girls' pubertal onset with MnBP, MMP, MEP and MEHP were significant. The odds of girls' breast onset were 4 to 10 times higher in high MnBP, MMP, MEP or MEHP exposure group than in low exposure group.
  
  
  CONCLUSIONS
  Our findings suggest subtle effects of phthalate metabolites associated with pubertal onset and progression. MnBP exposure may be associated with delayed pubic hair development in boys, while MnBP, MMP, MEP, and MEHP exposures may be associated with breast onset, and MEHP metabolites associated with speedup in breast development progression and earlier menarche onset in girls.
authors.affiliation: School of Public Health, Key Laboratory of Public Health Safety, Fudan University, Shanghai 200032, China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Unit of Biostatistics, Division of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm 17177, Sweden.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: School of Public Health, Key Laboratory of Public Health Safety, Fudan University, Shanghai 200032, China. Electronic address: hjshi@fudan.edu.cn.
authors.forename: Huijing
authors.initials: H
authors.lastname: Shi
authors.affiliation: School of Public Health, Key Laboratory of Public Health Safety, Fudan University, Shanghai 200032, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Jiang
authors.affiliation: School of Public Health, Key Laboratory of Public Health Safety, Fudan University, Shanghai 200032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Unit of Biostatistics, Division of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm 17177, Sweden.
authors.forename: Xin
authors.initials: X
authors.lastname: Fang
authors.affiliation: School of Public Health, Key Laboratory of Public Health Safety, Fudan University, Shanghai 200032, China.
authors.forename: Changming
authors.initials: C
authors.lastname: Xie
mesh_terms: D000293:Adolescent; D002648:Child; D002681:China; D002853:Chromatography, Liquid; D003430:Cross-Sectional Studies; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000652:urine*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D010795:Phthalic Acids / Q000652:urine*; D011446:Prospective Studies; D011627:Puberty / Q000187:drug effects*; D012727:Sex Characteristics; D053719:Tandem Mass Spectrometry
chemical_list: D004785:Environmental Pollutants; D010795:Phthalic Acids
keywords: Antiandrogenic effect; Environmental endocrine disruptors; Phthalates; Pubertal timing; Sexual maturation