Abstract
Introduction: The widespread consumption of hormonal contraceptives among young females has a large effect on serum metabolite levels which is usually overlooked. In addition to genetic and environmental factors, hormonal status and usage of hormonal contraceptives [1] appear to play mayor role on plasma metabolites.
Method: In this work we investigated the effects of oral contraceptives on serum metabolite levels using the targeted metabolomics data set of the Cooperative Health Research in South Tyrol (CHRIS) study [2], consisting of 175 quantified metabolites in 6,872 participants. To this end, linear regression models were fitted separately to each analyte using the log2 transformed concentration as a response variable and sex, age, BMI, self-reported fasting status, and a binary variable for usage of hormonal contraceptives as covariates. To avoid any confounding effect between sex and sex-hormone medication, the analysis was repeated considering only female samples.
Conclusions: Including the use of hormonal contraceptives as a covariate has an impact on the results for sex-associated metabolites, and, to a lesser extent, also on age-related metabolites. The other investigated covariates, however, remain unaffected. The analysis performed on female samples only suggested that almost half of all significant sex-related metabolites are misidentified when these medications are not considered.
Keywords: CHRIS study, targeted metabolomics, oral contraceptives
References:
[1] J.M. Ramsey, J.D. Cooper , B.W. Penninx , S. Bahn, Variation in serum biomarkers with sex and female hormonal status: implications for clinical tests. Sci Rep. (31) 2016 ; 6:26947.
[2] V.V. Hernandes, N. Dordevic, E.M. Hantikainen, B.B. Sigurdsson, S.V. Smárason, V. Garcia-Larsen, M. Gögele, G. Caprioli, I. Bozzolan, P.P. Pramstaller, J. Rainer, Age, Sex, Body Mass Index, Diet and Menopause Related Metabolites in a Large Homogeneous Alpine Cohort. Metabolites 12, 2022, 3: 205.
Acknowledgement:
- The CHRIS study was funded by the Department of Innovation, Research and University of the Autonomous Province of Bolzano-South Tyrol and supported by the European Regional Development Fund (FESR1157).