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.
Highlights
Use of hormonal contraception is widespread: around 80% of women from high-income countries have used oral contraceptive pills.[1,2] United Nations estimates the worldwide prevalence of hormonal contraception use among reproductive women in a union to be over 13%
The cross-sectional associations of contraceptive pills (COCPs) and progestin-only contraceptives (POCs) use with 75 metabolic measures are shown in Figure 1
The concentrations of total lipids in all lipoprotein subclasses were increased; the strongest associations were for the high-density lipoprotein (HDL) subclasses and for the smallest very-low-density lipoprotein (VLDL) subclasses
Summary
Use of hormonal contraception is widespread: around 80% of women from high-income countries have used oral contraceptive pills.[1,2] United Nations estimates the worldwide prevalence of hormonal contraception use among reproductive women in a union to be over 13%. Most previous studies have been cross-sectional and only assessed a limited range of traditional metabolic risk factors.[8] The few existing small longitudinal studies have suggested that the effects of COCPs on lipids and insulin resistance tend to appear shortly after starting the use, and that the effects do not worsen with continued use and that they reverse upon stopping.[8,14,17,18] Our work here provides a plethora of new molecular information on the influences of hormonal contraception on a wide range of circulating markers of high relevance in cardiovascular risk assessment and in individual considerations on the decision of contraception.
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