Albe Swanepoel1, Janette Bester2, Yolanda Kruger3, Elmarie Davoren3, Ilse du Preez4. 1. Faculty of Health Sciences, Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa. albe.swanepoel@nwu.ac.za. 2. Department of Physiology, Faculty of Health Sciences, School of Medicine, University of Pretoria, Pretoria, South Africa. 3. Human Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom, South Africa. 4. Human Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom, South Africa. ilse.dupreez@nwu.ac.za.
Abstract
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.
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.