The effect of combined oral contraceptives containing drospirenone and ethinylestradiol on serum levels of amino acids and acylcarnitines

Introduction Metabolome variations have long been associated with normal hormonal fluctuations, and similar effects, related to the use of early generation synthetic hormones as a means of contraception, have also been identified. Objective We investigated the serum amino acid and acylcarnitine profiles induced by the use of combined oral contraceptives (COCs) consisting of Ethinylestradiol (EE) and a 4th generation progestin, Drospirenone (DRSP). Method Gas chromatography mass spectrometry and liquid chromatography with tandem mass spectrometry was used to identify and quantify the serum amino acids and acyl carnitine levels in 24 controls, 25 DRSP/20EE users and 26 DRSP/30EE users. Results Of the 26 amino acid compounds measured, 13 showed significant variations in abundance between the control and COC user groups. Although none of the 21 acylcarnitine compounds detected were statistically significant with regards to group variations, a trend, related the EE concentration, was observed. The detected metabolome disparities corresponded to that identified for earlier generation COCs, all pointing toward increased oxidative stress levels in the user groups. Conclusion These findings suggest that the clinical complications associated with these COCs could, to some extent, be alleviated by the simultaneous use of antioxidants. The study also highlights the role that targeted metabolomics could play in the elucidation of the underlying mechanisms of drug-induced severe effects.

Automated summary

Metabolome variations induced by combined oral contraceptives containing Ethinylestradiol and Drospirenone were investigated, revealing significant differences in serum amino acids and acylcarnitine levels between user groups and controls. The findings suggest an increase in oxidative stress levels among contraceptive users, potentially alleviated by the concurrent use of antioxidants. Targeted metabolomics could play a crucial role in understanding the underlying mechanisms of drug-induced severe effects.