title: Exogenous estrogen as mediator of racial differences in bioactive insulin-like growth factor-I levels among postmenopausal women.
abstract: BACKGROUND
  The role of exogenous estrogen use in racial differences in insulin-like growth factor-I (IGF-I) levels which affect cancer risk is unclear. We investigated whether the relationship between race and circulating bioactive IGF-I proteins was mediated by exogenous estrogen and the extent to which exogenous estrogen influenced the race-IGF-I relationship in postmenopausal women.
  
  
  METHODS
  This cross-sectional study included 636 white and 133 African American postmenopausal women enrolled in an ancillary study of the Women's Health Initiative Observational Study. To assess exogenous estrogen use (nonusers [n = 262] vs users [n = 507]) as a mediator of the race-IGF-I relationship, we used the Baron-Kenny method and an estimation of the proportional change in the odd ratios for IGF-I levels on race plus a bootstrapping test for the significance of the mediation effect.
  
  
  RESULTS
  Compared with white women, African American women were more likely to have high IGF-I levels and less likely to use exogenous estrogen. After accounting for race, estrogen nonusers had higher IGF-I levels than estrogen users did. Among oral contraceptive ever users, exogenous estrogen had a strong mediation effect (67%; p = .018) in the race-IGF-I relationship. In the women with a history of hypertension, exogenous estrogen explained racial differences in IGF-I levels to a modest degree (23%; p = .029).
  
  
  CONCLUSIONS
  Exogenous estrogen use has a potentially important role in disparities in IGF-I bioactivity between postmenopausal African American and white women. A history of oral contraceptive use and hypertension may be part of the interconnected hormonal pathways related to racial differences in IGF-I levels.
authors.affiliation: Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston. sjung@mdanderson.org.
authors.forename: Su Yon
authors.initials: SY
authors.lastname: Jung
authors.affiliation: Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Mara Z
authors.initials: MZ
authors.lastname: Vitolins
authors.affiliation: Division of Cancer Prevention and Control, College of Medicine, Ohio State University, Columbus.
authors.forename: Electra D
authors.initials: ED
authors.lastname: Paskett
authors.affiliation: Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Shine
authors.initials: S
authors.lastname: Chang
mesh_terms: D001741:Black or African American / Q000706:statistics & numerical data*; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D015914:Estrogen Replacement Therapy / Q000379:methods; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008019:Life Style; D008875:Middle Aged; D009765:Obesity / Q000097:blood; D017698:Postmenopause / Q000097:blood* / Q000208:ethnology*; D012307:Risk Factors; D013781:Texas / Q000453:epidemiology; D044465:White People / Q000706:statistics & numerical data*
chemical_list: D015415:Biomarkers; D004967:Estrogens; D007334:Insulin-Like Growth Factor I
keywords: Exogenous estrogen; Insulin-like growth factor-I; Mediation; Postmenopausal women.