Extensive modulation of the circulating blood proteome by hormonal contraceptive use across two population studies
Abstract Background The study of circulating blood proteins in population cohorts offers new avenues to explore lifestyle-related and genetic influences describing and shaping human health. Methods Utilizing high-throughput mass spectrometry, we quantified 148 highly abundant proteins, functioning i...
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Nature Portfolio
2025-04-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-00856-0 |
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| author | Nikola Dordevic Clemens Dierks Essi Hantikainen Vadim Farztdinov Fatma Amari Vinicius Verri Hernandes Alessandro De Grandi Francisco S. Domingues Orr Shomroni Kathrin Textoris-Taube Vivien Bahr Hannah Schmid Ilja Demuth Florian Kurth Michael Mülleder Peter Paul Pramstaller Johannes Rainer Markus Ralser |
| author_facet | Nikola Dordevic Clemens Dierks Essi Hantikainen Vadim Farztdinov Fatma Amari Vinicius Verri Hernandes Alessandro De Grandi Francisco S. Domingues Orr Shomroni Kathrin Textoris-Taube Vivien Bahr Hannah Schmid Ilja Demuth Florian Kurth Michael Mülleder Peter Paul Pramstaller Johannes Rainer Markus Ralser |
| author_sort | Nikola Dordevic |
| collection | DOAJ |
| description | Abstract Background The study of circulating blood proteins in population cohorts offers new avenues to explore lifestyle-related and genetic influences describing and shaping human health. Methods Utilizing high-throughput mass spectrometry, we quantified 148 highly abundant proteins, functioning in the innate and adaptive immune system, coagulation and nutrient transport in 3632 blood plasma, and 500 serum samples from the CHRIS and BASE-II cross-sectional population studies, respectively. Through multiple regression analyses, we aimed to identify the main factors influencing the circulating proteome at population level. Results Many demographic covariates and common medications affect the concentration of high-abundant plasma proteins, but the most significant changes are linked to the use of hormonal contraceptives (HCU). HCU particularly alters amongst others the levels of Angiotensinogen and Transcortin. We robustly replicated these findings in the BASE-II cohort. Furthermore, our results indicate that combined hormonal contraceptives with ethinylestradiol have a stronger effect compared to bioidentical estrogens. Our analysis detects no lasting impact of hormonal contraceptives on the plasma proteome. Conclusions HCU is the dominant factor reshaping the high-abundant circulating blood proteome in two population studies. Given the high prevalence of HCU among young women, it is essential to account for this treatment in human proteome studies to avoid misinterpreting its impact as sex- or age-related effects. Although we did not investigate the influence of HCU-induced proteomic changes on human health, our data suggest that future studies on this topic are warranted. |
| format | Article |
| id | doaj-art-dbe548e98fb4439ab212e5c6db088ebf |
| institution | OA Journals |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-dbe548e98fb4439ab212e5c6db088ebf2025-08-20T02:28:42ZengNature PortfolioCommunications Medicine2730-664X2025-04-015111210.1038/s43856-025-00856-0Extensive modulation of the circulating blood proteome by hormonal contraceptive use across two population studiesNikola Dordevic0Clemens Dierks1Essi Hantikainen2Vadim Farztdinov3Fatma Amari4Vinicius Verri Hernandes5Alessandro De Grandi6Francisco S. Domingues7Orr Shomroni8Kathrin Textoris-Taube9Vivien Bahr10Hannah Schmid11Ilja Demuth12Florian Kurth13Michael Mülleder14Peter Paul Pramstaller15Johannes Rainer16Markus Ralser17Institute for Biomedicine, Eurac ResearchCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Institute for BiochemistryInstitute for Biomedicine, Eurac ResearchCharité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin Core Facility – High Throughput Mass SpectrometryCharité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin Core Facility – High Throughput Mass SpectrometryInstitute for Biomedicine, Eurac ResearchInstitute for Biomedicine, Eurac ResearchInstitute for Biomedicine, Eurac ResearchCharité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin Core Facility – High Throughput Mass SpectrometryCharité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin Core Facility – High Throughput Mass SpectrometryDepartment of Endocrinology and Metabolic Diseases (Including Division of Lipid Metabolism), Biology of Aging Working Group, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinDepartment of Endocrinology and Metabolic Diseases (Including Division of Lipid Metabolism), Biology of Aging Working Group, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinDepartment of Endocrinology and Metabolic Diseases (Including Division of Lipid Metabolism), Biology of Aging Working Group, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu BerlinCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Institute for BiochemistryCharité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin Core Facility – High Throughput Mass SpectrometryInstitute for Biomedicine, Eurac ResearchInstitute for Biomedicine, Eurac ResearchCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Institute for BiochemistryAbstract Background The study of circulating blood proteins in population cohorts offers new avenues to explore lifestyle-related and genetic influences describing and shaping human health. Methods Utilizing high-throughput mass spectrometry, we quantified 148 highly abundant proteins, functioning in the innate and adaptive immune system, coagulation and nutrient transport in 3632 blood plasma, and 500 serum samples from the CHRIS and BASE-II cross-sectional population studies, respectively. Through multiple regression analyses, we aimed to identify the main factors influencing the circulating proteome at population level. Results Many demographic covariates and common medications affect the concentration of high-abundant plasma proteins, but the most significant changes are linked to the use of hormonal contraceptives (HCU). HCU particularly alters amongst others the levels of Angiotensinogen and Transcortin. We robustly replicated these findings in the BASE-II cohort. Furthermore, our results indicate that combined hormonal contraceptives with ethinylestradiol have a stronger effect compared to bioidentical estrogens. Our analysis detects no lasting impact of hormonal contraceptives on the plasma proteome. Conclusions HCU is the dominant factor reshaping the high-abundant circulating blood proteome in two population studies. Given the high prevalence of HCU among young women, it is essential to account for this treatment in human proteome studies to avoid misinterpreting its impact as sex- or age-related effects. Although we did not investigate the influence of HCU-induced proteomic changes on human health, our data suggest that future studies on this topic are warranted.https://doi.org/10.1038/s43856-025-00856-0 |
| spellingShingle | Nikola Dordevic Clemens Dierks Essi Hantikainen Vadim Farztdinov Fatma Amari Vinicius Verri Hernandes Alessandro De Grandi Francisco S. Domingues Orr Shomroni Kathrin Textoris-Taube Vivien Bahr Hannah Schmid Ilja Demuth Florian Kurth Michael Mülleder Peter Paul Pramstaller Johannes Rainer Markus Ralser Extensive modulation of the circulating blood proteome by hormonal contraceptive use across two population studies Communications Medicine |
| title | Extensive modulation of the circulating blood proteome by hormonal contraceptive use across two population studies |
| title_full | Extensive modulation of the circulating blood proteome by hormonal contraceptive use across two population studies |
| title_fullStr | Extensive modulation of the circulating blood proteome by hormonal contraceptive use across two population studies |
| title_full_unstemmed | Extensive modulation of the circulating blood proteome by hormonal contraceptive use across two population studies |
| title_short | Extensive modulation of the circulating blood proteome by hormonal contraceptive use across two population studies |
| title_sort | extensive modulation of the circulating blood proteome by hormonal contraceptive use across two population studies |
| url | https://doi.org/10.1038/s43856-025-00856-0 |
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