title: Elevated phthalates' exposure in children with constitutional delay of growth and puberty.
abstract: BACKGROUND
  Phthalates have been proven to be antiandrogenic, which may interfere with the timing of puberty. Children with Constitutional Delay of Growth and Puberty (CDGP) typically display short stature and pubertal delay. This study investigated whether phthalate's exposure was associated with CDGP, and evaluated the potential mediator role of testosterone.
  
  
  METHODS
  In this case-control study, a total of 167 boys, including 57 boys with CDGP (cases) and 110 controls were enrolled. We measured six major phthalate metabolites in urine samples using high-performance liquid chromatography and tandem mass spectrometry (LC-MS/MS). The serum testosterone level was determined by radioimmunoassay.
  
  
  RESULTS
  Children in the CDGP group were determined to have significantly elevated urinary phthalates concentration compared with control subjects (total phthalates median: case, 107.00 ng/ml; control, 62.22 ng/ml, p = 0.001). After adjustment for BMI and other confounding factors: mono-n-butyl phthalate (MBP), monoethyl phthalate (MEP) and total phthalate concentrations were significantly negatively associated with serum testosterone level (MBP: β = -45.7, p = 0.017; MEP: β = -31.6, p = 0.022; total phthalates: β = -24.6, p = 0.011); MBP, MEP, mono (2-ethylhexyl) phthalate (MEHP) and total phthalates were significantly associated with CDGP (odds ratio: MBP: 8.30, p = 0.002; MEP: 5.43, p = 0.002; MEHP: 3.83, p = 0.017; total phthalates: 9.09, p = 0.001). Serum testosterone level acted as a mediator of the association between phthalates' exposure and CDGP (p = 0.002) (proportion mediated: 34.4%).
  
  
  CONCLUSIONS
  In this case-control study, elevated phthalates' level was detected in children with CDGP in Shanghai, China and phthalate level was associated with CDGP, which appeared to be mediated by circulating testosterone level.
authors.affiliation: Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Changming
authors.initials: C
authors.lastname: Xie
authors.affiliation: Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Lianlian
authors.initials: L
authors.lastname: Gao
authors.affiliation: Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Depei
authors.initials: D
authors.lastname: Cai
authors.affiliation: Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, China. Electronic address: yhzhang@shmu.edu.cn.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D001827:Body Height; D016022:Case-Control Studies; D002648:Child; D052244:Endocrine Disruptors / Q000652:urine*; D004785:Environmental Pollutants / Q000652:urine*; D006801:Humans; D008297:Male; D010795:Phthalic Acids / Q000652:urine*; D011627:Puberty; D011628:Puberty, Delayed / Q000097:blood / Q000503:physiopathology / Q000652:urine*; D012741:Sexual Maturation; D013739:Testosterone / Q000097:blood*
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D010795:Phthalic Acids; D013739:Testosterone
keywords: Constitutional Delay of Growth and Puberty; Mediating effects; Phthalate; Testosterone