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Sci Rep. 2017 Oct 26;7(1):14111. doi: 10.1038/s41598-017-13927-7.

Evidence for Stress-like Alterations in the HPA-Axis in Women Taking Oral Contraceptives.

Author information

1
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. hertelj@uni-greifswald.de.
2
German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany. hertelj@uni-greifswald.de.
3
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
4
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
5
German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany.
6
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
7
DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
8
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
9
Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
10
Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
11
IEG (Institute of Experimental Genetics), Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany.
12
Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, Doha, Qatar.
13
DZD (German Center for Diabetes Research), site München-Neuherberg, Neuherberg, Germany.
14
Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany.
15
Institute of Diagnostic Radiology, University Medicine Greifswald, Greifswald, Germany.
16
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
17
Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark.

Abstract

Using oral contraceptives has been implicated in the aetiology of stress-related disorders like depression. Here, we followed the hypothesis that oral contraceptives deregulate the HPA-axis by elevating circulating cortisol levels. We report for a sample of 233 pre-menopausal women increased circulating cortisol levels in those using oral contraceptives. For women taking oral contraceptives, we observed alterations in circulating phospholipid levels and elevated triglycerides and found evidence for increased glucocorticoid signalling as the transcript levels of the glucocorticoid-regulated genes DDIT4 and FKBP5 were increased in whole blood. The effects were statistically mediated by cortisol. The associations of oral contraceptives with higher FKBP5 mRNA and altered phospholipid levels were modified by rs1360780, a genetic variance implicated in psychiatric diseases. Accordingly, the methylation pattern of FKBP5 intron 7 was altered in women taking oral contraceptives depending on the rs1360780 genotype. Moreover, oral contraceptives modified the association of circulating cortisol with depressive symptoms, potentially explaining conflicting results in the literature. Finally, women taking oral contraceptives displayed smaller hippocampal volumes than non-using women. In conclusion, the integrative analyses of different types of physiological data provided converging evidence indicating that oral contraceptives may cause effects analogous to chronic psychological stressors regarding the regulation of the HPA axis.

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