title: Ultrasensitive estrogen levels at 7 years of age predict earlier thelarche: evidence from girls of the growth and obesity Chilean cohort.
abstract: OBJECTIVE
  Prepubertal estradiol equivalents have been inconsistently linked to age at thelarche; elucidating this relationship becomes relevant given the worldwide decline in the age of puberty onset. Thus, our aim is to assess whether prepubertal girls with higher serum levels of estradiol equivalents at age 7 have a greater risk of presenting early thelarche (ET).
  
  
  METHODS
  Nested case-control study within the Growth and Obesity Cohort Study of 1196 low-middle income children (∼50% girls) from Santiago, Chile. Girls were defined as cases (ET; n=61) if breast bud appeared prior to 8 years of age; controls (n=91) had thelarche >8 years.
  
  
  METHODS
  At 6.7 years, weight, height and waist circumference were measured and a fasting blood sample was obtained for measuring estrogen equivalent (ultrasensitive recombinant cell bioassay), DHEAS, leptin, insulin and IGF1. Beginning at 7 years old, Tanner staging was assessed prospectively twice a year and the appearance of breast bud was assessed by palpation.
  
  
  RESULTS
  Mean serum estradiol-equivalent at 6.7 years was 3.9±3.6 pg/ml for cases and 3.6±2.3 pg/ml for controls. Girls with ET had a higher risk of presenting elevated estradiol-equivalent (≥5 pg/ml) at 7 years (OR=2.05, 95% CI: 0.96-4.36) than controls that was borderline significant. However, after adjusting by BMI, insulin and IGF1 at age 7, the association between estradiol-equivalent and ET was significant (OR=2.29 (95% CI: 1.05-5.01)).
  
  
  CONCLUSIONS
  Chilean girls from low to middle socioeconomic status with ET exhibited double the risk of having high levels of estradiol-equivalent at 7 years than girls with a later age of thelarche. Whole-body adiposity and increased adrenal activity did not explain the observed prepubertal estrogen increase.
authors.affiliation: Institute of Nutrition and Food TechnologyUniversity of Chile, Avenida El Líbano 5524, Macul, Santiago, ChileDepartment of NeonatologyFaculty of Medicine, Catholic University of Chile, Santiago, ChileDepartment of PediatricsUniversity of California, San Diego, California, USAInstitute of Maternal and Child ResearchFaculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Ana
authors.initials: A
authors.lastname: Pereira
authors.affiliation: Institute of Nutrition and Food TechnologyUniversity of Chile, Avenida El Líbano 5524, Macul, Santiago, ChileDepartment of NeonatologyFaculty of Medicine, Catholic University of Chile, Santiago, ChileDepartment of PediatricsUniversity of California, San Diego, California, USAInstitute of Maternal and Child ResearchFaculty of Medicine, University of Chile, Santiago, Chile ccorvalan@inta.uchile.cl ccorval@gmail.com.
authors.forename: Camila
authors.initials: C
authors.lastname: Corvalán
authors.affiliation: Institute of Nutrition and Food TechnologyUniversity of Chile, Avenida El Líbano 5524, Macul, Santiago, ChileDepartment of NeonatologyFaculty of Medicine, Catholic University of Chile, Santiago, ChileDepartment of PediatricsUniversity of California, San Diego, California, USAInstitute of Maternal and Child ResearchFaculty of Medicine, University of Chile, Santiago, Chile Institute of Nutrition and Food TechnologyUniversity of Chile, Avenida El Líbano 5524, Macul, Santiago, ChileDepartment of NeonatologyFaculty of Medicine, Catholic University of Chile, Santiago, ChileDepartment of PediatricsUniversity of California, San Diego, California, USAInstitute of Maternal and Child ResearchFaculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Uauy
authors.affiliation: Institute of Nutrition and Food TechnologyUniversity of Chile, Avenida El Líbano 5524, Macul, Santiago, ChileDepartment of NeonatologyFaculty of Medicine, Catholic University of Chile, Santiago, ChileDepartment of PediatricsUniversity of California, San Diego, California, USAInstitute of Maternal and Child ResearchFaculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Karen O
authors.initials: KO
authors.lastname: Klein
authors.affiliation: Institute of Nutrition and Food TechnologyUniversity of Chile, Avenida El Líbano 5524, Macul, Santiago, ChileDepartment of NeonatologyFaculty of Medicine, Catholic University of Chile, Santiago, ChileDepartment of PediatricsUniversity of California, San Diego, California, USAInstitute of Maternal and Child ResearchFaculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Verónica
authors.initials: V
authors.lastname: Mericq
mesh_terms: D050154:Adiposity; D001940:Breast / Q000254:growth & development*; D016022:Case-Control Studies; D002648:Child; D002677:Chile; D015331:Cohort Studies; D004958:Estradiol / Q000097:blood*; D005260:Female; D006801:Humans; D011627:Puberty; D011629:Puberty, Precocious / Q000097:blood*
chemical_list: D004958:Estradiol