Margherita Ruoppolo1, Ilaria Campesi2, Emanuela Scolamiero3, Rita Pecce4, Marianna Caterino5, Sara Cherchi6, Giuseppe Mercuro7, Giancarlo Tonolo6, Flavia Franconi8. 1. Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II" Napoli, Italy ; CEINGE Biotecnologie Avanzate scarl Napoli, Italy. 2. Department of Biomedical Sciences, University of Sassari Sassari, Italy ; National Laboratory of Gender Medicine of the National Institute of Biostructures and Biosystems Osilo, Italy. 3. CEINGE Biotecnologie Avanzate scarl Napoli, Italy. 4. Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II" Napoli, Italy. 5. Fondazione SDN-IRCCS Napoli, Ital. 6. SC Diabetologia Aziendale ASL 2 Olbia, San Giovanni di Dio Hospita Olbia, Italy. 7. Department of Medical Sciences, University of Cagliari Italy. 8. Department of Biomedical Sciences, University of Sassari Sassari, Italy ; National Laboratory of Gender Medicine of the National Institute of Biostructures and Biosystems Osilo, Italy ; Centre of Excellence for Biotechnology Development and Biodiversity Research, University of Sassari Sassari, Italy.
Abstract
AIM: Considering that the effects of sex and oral contraceptives (OCs) on blood metabolites have been scarcely studied 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: Healthy adult men and women were enrolled. They were drug free with the exception of women taking cyclic format OCs (ethinylestradiol + different progestins). OCs-free women were analysed during the follicular phase, and amino acids, free carnitine and acylcarnitines were measured using HPLC or LC-MS/MS, respectively. RESULTS: Men had significantly higher leucine, isoleucine, methionine, asparagine, proline, valine, tyrosine, glutamine+glutamate, glutamate, histidine and citrulline than OCs-free women, while tryptophan was significantly lower in men. OCs use significantly decreased the levels of glycine, proline, histidine, lysine, hydroxyproline and ornithine and increased isoleucine levels when compared with non-user women. OCs use reduced, although not significantly, carnitine levels in women. Total esterified carnitines were higher in untreated women than in OCs 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. CONCLUSIONS: 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 OCs users and non-users should be represented in clinical trials.
AIM: Considering that the effects of sex and oral contraceptives (OCs) on blood metabolites have been scarcely studied 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: Healthy adult men and women were enrolled. They were drug free with the exception of women taking cyclic format OCs (ethinylestradiol + different progestins). OCs-free women were analysed during the follicular phase, and amino acids, free carnitine and acylcarnitines were measured using HPLC or LC-MS/MS, respectively. RESULTS:Men had significantly higher leucine, isoleucine, methionine, asparagine, proline, valine, tyrosine, glutamine+glutamate, glutamate, histidine and citrulline than OCs-free women, while tryptophan was significantly lower in men. OCs use significantly decreased the levels of glycine, proline, histidine, lysine, hydroxyproline and ornithine and increased isoleucine levels when compared with non-user women. OCs use reduced, although not significantly, carnitine levels in women. Total esterified carnitines were higher in untreated women than in OCs 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. CONCLUSIONS: 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 OCs users and non-users should be represented in clinical trials.
Entities:
Keywords:
Amino acids; acylcarnitines; carnitine; metabolomics; oral contraceptives; sex
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