title: Novel effects of hormonal contraceptive use on the plasma proteome.
abstract: BACKGROUND
  Hormonal contraceptive (HC) use may increase cardiometabolic risk; however, the effect of HC on emerging cardiometabolic and other disease risk factors is not clear.
  
  
  OBJECTIVE
  To determine the association between HC use and plasma proteins involved in established and emerging disease risk pathways.
  
  
  METHODS
  Concentrations of 54 high-abundance plasma proteins were measured simultaneously by LC-MRM/MS in 783 women from the Toronto Nutrigenomics and Health Study. C-reactive protein (CRP) was measured separately. ANCOVA was used to test differences in protein concentrations between users and non-users, and among HC users depending on total hormone dose. Linear regression was used to test the association between duration (years) of HC use and plasma protein concentrations. Principal components analysis (PCA) was used to identify plasma proteomic profiles in users and non-users.
  
  
  RESULTS
  After Bonferroni correction, 19 proteins involved in inflammation, innate immunity, coagulation and blood pressure regulation were significantly different between users and non-users (P<0.0009). These differences were replicated across three distinct ethnocultural groups. Traditional markers of glucose and lipid metabolism were also significantly higher among HC users. Neither hormone dose nor duration of use affected protein concentrations. PCA identified 4 distinct proteomic profiles in users and 3 in non-users.
  
  
  CONCLUSIONS
  HC use was associated with different concentrations of plasma proteins along various disease-related pathways, and these differences were present across different ethnicities. Aside from the known effect of HC on traditional biomarkers of cardiometabolic risk, HC use also affects numerous proteins that may be biomarkers of dysregulation in inflammation, coagulation and blood pressure.
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Josse
authors.forename: Bibiana
authors.initials: B
authors.lastname: Garcia-Bailo
authors.forename: Karina
authors.initials: K
authors.lastname: Fischer
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Sohemy
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins / Q000032:analysis*; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood / Q000139:chemically induced / Q000378:metabolism; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016014:Linear Models; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D025341:Principal Component Analysis; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D001798:Blood Proteins; D003278:Contraceptives, Oral, Hormonal; D020543:Proteome; D002097:C-Reactive Protein