Metabolomics profile of 5649 users and non-users of hormonal intrauterine devices in Finland

Open AccessPublished:June 10, 2022DOI:
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      Use of hormonal intrauterine devices has grown during the last decades. Although the hormonal intrauterine devices act mostly via local effects on uterus, measurable concentrations of levonorgestrel are absorbed into the systemic circulation. The possible metabolic changes and large scale biomarker profiles associated with the hormonal intrauterine devices have not yet been studied in detail.


      To examine, through the metabolomics approach, the metabolic profile of the hormonal intrauterine device use, its associations as a function of the duration of use, as well as those with after discontinuation of the hormonal intrauterine device use.

      Study Design

      The study consists of cross-sectional analyses of five population-based surveys (FINRISK and FinHealth studies), spanning 1997-2017. All fertile aged (18-49 years) participants in the surveys with available information on hormonal contraceptive use and metabolomics data (n=5649), were included in the study. Altogether 211 metabolic measures in users of hormonal intrauterine devices (n=1006) were compared to those in non-users of hormonal contraception (n=4643) via multivariable linear regression models. In order to allow the comparison across multiple measures, association magnitudes are reported in SD units of difference in biomarker concentration compared to the reference group.


      After adjustment for covariates, levels of 141 metabolites differed in current users of hormonal intrauterine devices compared to non-users of hormonal contraception (median difference in biomarker concentration: 0.09 SD): lower levels of particle concentration of larger lipoprotein subclasses, triglycerides, cholesterol and derivatives, apolipoproteins A and B, fatty acids, glycoprotein acetyls and aromatic amino acids. The metabolic pattern of the hormonal intrauterine device use did not change according to the duration of use. When comparing previous users and never-users of hormonal intrauterine devices, no significant metabolic differences emerged.


      The use of hormonal intrauterine devices was associated with several moderate metabolic changes, previously associated with reduced arterial cardiometabolic risk. The metabolic effects were independent of the duration of use of the hormonal intrauterine devices. Moreover, the metabolic profiles were similar after discontinuation of the hormonal intrauterine devices and in never-users.