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Original Research: Gynecology|Articles in Press

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

Open AccessPublished:June 10, 2022DOI:https://doi.org/10.1016/j.ajog.2022.06.009
Metabolomics profile of 5649 users and non-users of hormonal intrauterine devices in Finland
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      Abstract

      Background

      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.

      Objectives

      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.

      Results

      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.

      Conclusions

      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.

      Keywords

      Article Info

      Publication History

      Accepted: June 6, 2022
      Received in revised form: June 3, 2022
      Received: April 12, 2022

      Publication stage

      In Press Journal Pre-Proof

      Footnotes

      Disclosure statement. OH serves occasionally on advisory boards for Bayer AG and Gedeon Richter, and has designed and lectured at educational events of these companies. The other authors report no conflict of interest.

      Funding. The study was supported by the Jane and Aatos Erkko Foundation (JH; grant number #170062), the Avohoidon tutkimussäätiö (JH; Foundation for Primary Care Research), the Yrjö Jahnsson Foundation (ET; grant number #20207328) and the Finnish Cultural Foundation (ET; grant number #00211101). None of the funders were involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

      Paper presentation information. The findings reported in this paper were presented at the 69th Annual Scientific Meeting of the Society for Reproductive Investigation, Denver, CO; March, 15-19, 2022.

      Condensation. The use of hormonal intrauterine devices was associated with several modest metabolic changes, suggestive of reduced cardiometabolic risk.

      AJOG at a Glance.

      A. Why was this study conducted?

      The use of hormonal intrauterine devices is increasing globally, and many users opt for subsequent device(s). Thus, an increasing number of fertile aged individuals are exposed for several years to Levonorgestrel, calling for assessment of possibly related metabolic changes and large scale biomarker profiles.

      B. What are the key findings?

      After adjustment for covariates, levels of 141 metabolites differed between current users of a hormonal intrauterine devices and non-users of hormonal contraception. The metabolic patterns were similar irrespective of the duration of use; most of the metabolic alterations were not evident in previous users.

      C. What does this study add to what is already known?

      The use of hormonal intrauterine devices is associated with many multiple moderate metabolic changes, suggestive of reduced arterial cardiometabolic risk. The associations appeared mostly to be independent on the duration of use, and not to persist after discontinuation of use.

      Identification

      DOI: https://doi.org/10.1016/j.ajog.2022.06.009

      Copyright

      © 2022 The Author(s). Published by Elsevier Inc.

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