Serum metabolomic profiles suggest influence of sex and oral contraceptive use.

Background The effects of sex and oral contraceptives (OCs) on blood metabolites have been scarcely studied. Considering the widespread use of OCs and the fact that protocol designs for clinical trials emphasise the use of contraception for women of childbearing potential, we examined if OCs and sex affect the serum levels of the physiologically relevant amino acids, carnitine and acylcarnitines, using metabolomics approaches. Methods Thirty-five healthy adult men and 67 women aged between 20 and 47 years were enrolled. They were drug free with the exception of women taking cyclic format OCs that contained ethinylestradiol and different progestins. OC-free women were analysed during the first ten days of their menstrual cycles, and amino acids, free carnitine and acylcarnitines were measured using HPLC or LC/MS/MS. Results The serum levels of alanine, serine, aspartic acid, arginine and taurine were not significantly different among the analysed groups. Men had significantly higher leucine, isoleucine, methionine, phenylalanine, asparagine, glutamine + glutamate, and histidine than women who did not use OCs, while tryptophan was significantly lower in men. OC use significantly decreased the levels of glycine, proline, glutamine + glutamate, lysine, hydroxyproline and ornitine when compared with non-user women. The level of free carnitine was higher in men than in women; in addition, OC use further reduced the levels of carnitine in women although the reduction is not significant. Total esterified carnitines were higher in untreated women when compared with that of men and OC users. Globally, the effect of OCs and sex was specific for the individual esterified carnitine. The observed metabolic changes were not attributable to renal or hepatic functions or to differences in body weight. Conclusion The assessed parameters were specifically influenced by sex, highlighting the need to have reference values for women and men. The major novelty of this study is the demonstration that OCs specifically change the profiles of serum amino acids and carnitine, which suggests that OC users and non-users should be represented in clinical trials.