Cross-sectional and longitudinal metabolomics-based profiles associated with oral contraceptive and progestin-only pill use: A Finnish population-based study.

Introduction: The use of combined oral contraceptives (COCs), but not of progestin-only pills (POPs) is associated with an increased risk of cardiovascular events. A detailed examination of how different oral contraceptives impact the metabolism in the short- and long-term has not been conducted. This study comparatively examines cross-sectional and longitudinal metabolomics-based profiles of different COCs and POPs, and explores how they perform relative to a metabolically safer contraceptive option.

Material and methods: Data were obtained from a population-based survey (Health 2000) and its 11-year follow-up (Health 2011). Altogether, 212 metabolic measures in OC users (n = 299; COC, n = 245; POP, n = 33) were compared to those in non-users of hormonal contraception (HC; n = 1422), and in users of a levonorgestrel intrauterine device (LNG-IUD; n = 341) via multivariable general estimating equations models adjusted for age, body mass index, duration of use, study cohort, diseases, medication use, alcohol use, smoking, and physical activity. Participants with complete longitudinal information (n = 327) were divided into continuers, stoppers, starters, switchers, and never-user groups, and the 11-year changes in the levels of each metabolite were compared.

Results: Use of COCs, but not of POPs, was associated with altered levels of several metabolic measures compared to HC non-use or to use of LNG-IUD: higher concentrations and ratios of monounsaturated fatty acids but lower ratios of polyunsaturated fatty acids, and higher concentrations and ratios of triglycerides in lipoproteins. Additionally, in comparison to HC non-use or to use of LNG-IUD, users of third generation or other COCs had higher levels of inflammation markers and of cholesterol, but a lower percentage of cholesterol and a higher percentage of triglycerides in lipoproteins. Continuation or starting of LNG-IUD was not related to changes in metabolic profiles, while women who changed or stopped using COCs had greater levels of unsaturation and lower levels of total and lipoprotein triglycerides and other lipids.

Conclusions: The use of COCs, especially of third generation and other COCs, is related to various metabolic alterations suggestive of increased cardiovascular risk. Conversely, the use of POPs and LNG-IUD appeared metabolically safe. These associations were mostly reversible after interruption of use or switch to different preparations.