title: Effects of hormonal contraception on systemic metabolism: cross-sectional and longitudinal evidence.
abstract: Hormonal contraception is commonly used worldwide, but its systemic effects across lipoprotein subclasses, fatty acids, circulating metabolites and cytokines remain poorly understood.
  
  
  
  A comprehensive molecular profile (75 metabolic measures and 37 cytokines) was measured for up to 5841 women (age range 24-49 years) from three population-based cohorts. Women using combined oral contraceptive pills (COCPs) or progestin-only contraceptives (POCs) were compared with those who did not use hormonal contraception. Metabolomics profiles were reassessed for 869 women after 6 years to uncover the metabolic effects of starting, stopping and persistently using hormonal contraception.
  
  
  
  The comprehensive molecular profiling allowed multiple new findings on the metabolic associations with the use of COCPs. They were positively associated with lipoprotein subclasses, including all high-density lipoprotein (HDL) subclasses. The associations with fatty acids and amino acids were strong and variable in direction. COCP use was negatively associated with albumin and positively associated with creatinine and inflammatory markers, including glycoprotein acetyls and several growth factors and interleukins. Our findings also confirmed previous results e.g. for increased circulating triglycerides and HDL cholesterol. Starting COCPs caused similar metabolic changes to those observed cross-sectionally: the changes were maintained in consistent users and normalized in those who stopped using. In contrast, POCs were only weakly associated with metabolic and inflammatory markers. Results were consistent across all cohorts and for different COCP preparations and different types of POC delivery.
  
  
  
  Use of COCPs causes widespread metabolic and inflammatory effects. However, persistent use does not appear to accumulate the effects over time and the metabolic perturbations are reversed upon discontinuation. POCs have little effect on systemic metabolism and inflammation.
authors.affiliation: Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu, Finland.|NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu, Finland.
authors.forename: Peter
authors.initials: P
authors.lastname: Würtz
authors.forename: Kirsi
authors.initials: K
authors.lastname: Auro
authors.affiliation: Department of Obstetrics and Gynecology, Oulu University Hospital, University of Oulu and Medical Research Center Oulu, Oulu, Finland.
authors.forename: Laure
authors.initials: L
authors.lastname: Morin-Papunen
authors.affiliation: Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu, Finland.
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Kangas
authors.affiliation: Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu, Finland.|NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.affiliation: Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu, Finland.|NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Tiainen
authors.affiliation: Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu, Finland.|NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Tuulia
authors.initials: T
authors.lastname: Tynkkynen
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.|Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Anni
authors.initials: A
authors.lastname: Joensuu
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.|Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Aki S
authors.initials: AS
authors.lastname: Havulinna
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
authors.forename: Kristiina
authors.initials: K
authors.lastname: Aalto
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Salmi
authors.affiliation: Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK e.V.), partner site Hamburg, Lübeck, Kiel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.affiliation: Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.|German Center for Cardiovascular Research (DZHK e.V.), partner site Hamburg, Lübeck, Kiel, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
authors.affiliation: Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Viikari
authors.affiliation: Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.affiliation: Department of Clinical Chemistry, Fimlab Laboratories, School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.|Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland.|Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.affiliation: Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.|Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
authors.forename: Olli T
authors.initials: OT
authors.lastname: Raitakari
authors.affiliation: Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK and.|School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Lawlor
authors.forename: Johannes
authors.initials: J
authors.lastname: Kettunen
authors.affiliation: Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu, Finland, mika.ala-korpela@com.|NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.|Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK and.|Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
mesh_terms: D000328:Adult; D008076:Cholesterol, HDL / Q000097:blood*; D003278:Contraceptives, Oral, Hormonal / Q000494:pharmacology*; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood; D005227:Fatty Acids / Q000097:blood; D005260:Female; D005387:Finland; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics; D011372:Progestins / Q000494:pharmacology*; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*; D055815:Young Adult
chemical_list: D008076:Cholesterol, HDL; D003278:Contraceptives, Oral, Hormonal; D016207:Cytokines; D005227:Fatty Acids; D011372:Progestins; D014280:Triglycerides
keywords: amino acids; combined oral contraceptive pills; cytokines; fatty acids; hormonal contraception; hormones; inflammation; lipoproteins; metabolomics; progestin-only contraceptives; risk factors