Metabolomic Profiling of Hormonal Contraceptive Use in Young Females Using a Commercially Available LC-MS/MS Kit

Abstract

Oral hormonal contraceptive users carry the risk of venous thrombosis and increased mortality. This study aimed to comprehensively profile the serum metabolome of participants using a combination of drospirenone (DRSP) and ethinyl estradiol (EE) containing oral contraceptives (COCs). The MxP Quant 500 kit for liquid chromatography mass tandem spectrometry (LC-MS/MS) was used to analyse the 22 controls and 44 COC users (22 on a low EE dose (DRSP/20EE) and 22 on a higher EE dose (DRSP/30EE)). The kit’s results were compared to our internally developed untargeted and targeted metabolomics methods previously applied to this cohort. Of the 630 metabolites included in the method, 277 provided desirable results (consistently detected above their detection limits), and of these, 5 had p-values < 0.05, including betaine, glutamine, cortisol, glycine, and choline. Notably, these variations were observed between the control and COC groups, rather than among the two COC groups. Partial least squares-discriminant analysis revealed 49 compounds with VIP values ≥ 1, including amino acids and their derivatives, ceramides, phosphatidylcholines, and triglycerides, among others. Ten differential compounds were consistent with our previous studies, reinforcing the notion of COCs inducing a prothrombotic state and increased oxidative stress. Although only a limited number of compounds were deemed usable, these were quantified with high reliability and facilitated the identification of meaningful biological differences among the sample groups. In addition to substantiating known drug-induced variations, new hypotheses were also generated.