Effects of hormonal contraception on systemic metabolism: cross-sectional and longitudinal evidence

Qin Wang, Peter Würtz, Kirsi Auro, Laure Morin-Papunen, Antti J Kangas, Pasi Soininen, Mika Tiainen, Tuulia Tynkkynen, Anni Joensuu, Aki S Havulinna, Kristiina Aalto, Marko Salmi, Stefan Blankenberg, Tanja Zeller, Jorma Viikari, Mika Kähönen, Terho Lehtimäki, Veikko Salomaa, Sirpa Jalkanen, Marjo-Riitta JärvelinMarkus Perola, Olli T Raitakari, Debbie A Lawlor, Johannes Kettunen, Mika Ala-Korpela

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

BACKGROUND: Hormonal contraception is commonly used worldwide, but its systemic effects across lipoprotein subclasses, fatty acids, circulating metabolites and cytokines remain poorly understood.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

Original languageEnglish
Pages (from-to)1445-1457
Number of pages13
JournalInternational Journal of Epidemiology
Volume45
Issue number5
Early online date18 Aug 2016
DOIs
Publication statusPublished - Oct 2016

Keywords

  • hormonal contraception
  • combined oral contraceptive pills
  • progestin-only contraceptives
  • metabolomics
  • cytokines
  • inflammation
  • amino acids
  • fatty acids
  • lipoproteins
  • hormones
  • risk factors

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