{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:56:06Z","timestamp":1787028966478,"version":"build-2736575974"},"reference-count":85,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T00:00:00Z","timestamp":1616544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>The use of oral contraceptives (OCs) has been associated with elevated blood cortisol concentrations. However, metabolic downstream effects of OC intake are not well described. Here, we aimed to determine if the blood metabolome is associated with the use of OCs and to estimate if these associations might be statistically mediated by serum cortisol concentrations. Plasma metabolites measured with the Biocrates AbsoluteIDQ p180 Kit and serum cortisol concentrations measured by an immunoassay were determined in 391 premenopausal women (116 OC users) participating in two independent cohorts of the Study of Health in Pomerania (SHIP). After correction for multiple testing, 27 metabolites were significantly associated with OC intake in SHIP-TREND (discovery cohort), of which 25 replicated in SHIP-2. Inter alia, associated metabolites included 12 out of 38 phosphatidylcholines with diacyl residue, 7 out of 14 lysophosphatidylcholines and 5 out of 21 amino acids. The associations with phosphatidylcholines were statistically mediated by cortisol, whereas lysophosphatidylcholines showed no mediation effect. The results represent a step toward a better understanding of the metabolic consequences of OC intake. Connecting cortisol with metabolic consequences of OC intake could help to understand the mechanisms underlying adverse effects. The blood metabolome may serve as a biomarker for identifying users at high risk for developing such adverse effects.<\/jats:p>","DOI":"10.3390\/metabo11040193","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T15:42:19Z","timestamp":1616600539000},"page":"193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Broad Metabolome Alterations Associated with the Intake of Oral Contraceptives Are Mediated by Cortisol in Premenopausal Women"],"prefix":"10.3390","volume":"11","author":[{"given":"Clara","family":"Eick","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, D-17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2287-7914","authenticated-orcid":false,"given":"Johanna","family":"Klinger-K\u00f6nig","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, D-17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7417-4407","authenticated-orcid":false,"given":"Stephanie","family":"Zylla","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17489 Greifswald, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, D-17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4420-5449","authenticated-orcid":false,"given":"Anke","family":"Hannemann","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17489 Greifswald, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, D-17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Budde","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann Kristin","family":"Henning","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maik","family":"Pietzner","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Nauck","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17489 Greifswald, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, D-17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"V\u00f6lzke","sequence":"additional","affiliation":[{"name":"German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, D-17489 Greifswald, Germany"},{"name":"Institute for Community Medicine, University Medicine Greifswald, D-17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J.","family":"Grabe","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, D-17489 Greifswald, Germany"},{"name":"German Center for Neurodegenerative Disease (DZNE), Site Rostock\/Greifswald, D-17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Hertel","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, D-17489 Greifswald, Germany"},{"name":"School of Medicine, National University of Ireland, H91 CF50 Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,24]]},"reference":[{"key":"ref_1","unstructured":"(2017). 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