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Metabolomics profile of 5649 users and nonusers of hormonal intrauterine devices in Finland - 28/09/22

Doi : 10.1016/j.ajog.2022.06.009 
Elena Toffol, MD, PhD a, , Oskari Heikinheimo, MD, PhD b, Pekka Jousilahti, MD, PhD c, Anna But, PhD a, Anni Joensuu, MSc d, Antti Latvala, PhD e, Timo Partonen, MD, PhD c, Iris Erlund, PhD f, Jari Haukka, PhD a
a Department of Public Health, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland 
b Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland 
c Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland 
d Department of Knowledge Brokers, Finnish Institute for Health and Welfare, Helsinki, Finland 
e Institute of Criminology and Legal Policy, University of Helsinki, Helsinki, Finland 
f Department of Government Services, Finnish Institute for Health and Welfare, Helsinki, Finland 

Corresponding author: Elena Toffol, MD, PhD.

Abstract

Background

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

Objective

To examine through the metabolomics approach the metabolic profile of patients using hormonal intrauterine devices and how this metabolic profile is affected by duration and discontinuation of use.

Study Design

The study consisted of cross-sectional analyses of 5 population-based surveys (FINRISK and FinHealth studies), spanning from 1997 to 2017. All fertile-aged participants (18–49 years) in the surveys with available information on hormonal contraceptive use and metabolomics data (n=5649) were included in the study. Altogether, 211 metabolic measures of users of hormonal intrauterine devices (n=1006) were compared with those of nonusers of hormonal contraception (n=4643) via multivariable linear regression models. To allow comparison across multiple measures, association magnitudes were reported in standard deviation units of difference in biomarker concentration compared with the reference group.

Results

After adjustment for covariates, levels of 141 metabolites differed in current users of hormonal intrauterine devices compared with nonusers of hormonal contraception (median difference in biomarker concentration, 0.09 standard deviation): 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 hormonal intrauterine device use did not change according to duration of use. When comparing previous users and never-users of hormonal intrauterine devices, no significant metabolic differences were observed.

Conclusion

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 duration of use of the hormonal intrauterine devices. Moreover, the metabolic profiles were similar after discontinuation of hormonal intrauterine device use and in never-users.

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Key words : discontinuation of use, duration of use, fertile-aged, hormonal intrauterine devices, metabolic changes, metabolites


Plan


 O.H. 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.
 The study was supported by the Jane and Aatos Erkko Foundation (J.H.; grant number #170062), the Avohoidon Tutkimussäätiö (J.H.; Foundation for Primary Care Research), the Yrjö Jahnsson Foundation (E.T.; grant number #20207328), and the Finnish Cultural Foundation (E.T.; 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.
 Data availability: The individual level data used in this manuscript is available through THL Biobank at for-researchers.
 Cite this article as: Toffol E, Heikinheimo O, Jousilahti P, et al. Metabolomics profile of 5649 users and nonusers of hormonal intrauterine devices in Finland. Am J Obstet Gynecol 2022;227:603.e1-29.


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Vol 227 - N° 4

P. 603.e1-603.e29 - octobre 2022 Retour au numéro
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