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ADMA concentration changes across the menstrual cycle and during oral contraceptive use: the Cardiovascular Risk in Young Finns Study

Departments of
¹ Clinical Chemistry
² Obstetrics and Gynaecology, Kuopio University Hospital and University of Kuopio, FIN-70210 Kuopio, Finland, Departments of
³ Clinical Physiology
⁴ Internal Medicine, University of Turku, FIN-20520 Turku, Finland
⁵ Disease Risk Unit, National Institute of Health and Welfare, FIN-00271 Helsinki, Finland
⁶ Department of Clinical Physiology, Tampere University Hospital and University of Tampere, FIN-33520 Tampere, Finland
⁷ Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Medical School, Centre for Laboratory Medicine and University of Tampere, Tampere University Hospital, FIN-33520 Tampere, Finland
⁸ Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and University of Kuopio, FIN-70210 Kuopio, Finland

(Correspondence should be addressed to P Valtonen; Email: pirjo.valtonen{at}uku.fi)

Objective: The aim of this study was to evaluate changes in the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) levels during different menstrual cycle phases in young adult women with or without oral contraceptive (OC) use.

Design and methods: The subjects (n=1079) originated from a large population-based, prospective cohort study conducted in Finland. Plasma ADMA, symmetric dimethylarginine (SDMA), L-arginine, C-reactive protein, creatinine, and brachial artery flow-mediated dilatation (FMD) were measured. The use of OCs and menstrual cycle phase were determined from a questionnaire.

Results: In non-OC users, ADMA (P=0.017), L-arginine (P=0.002), and ADMA/SDMA ratio (P<0.001) were significantly lower in the luteal phase than in the follicular phase of the menstrual cycle. Non-OC users also had significantly higher ADMA and SDMA concentrations (P<0.001) and lower L-arginine concentrations (P<0.001) compared to OC users of estrogen-containing pills. Progestin-only contraceptive pills (POPs) did not lower the ADMA level, but maintained it at the same level as in non-OC users. In OC users, there were no significant differences found in ADMA, FMD, or FMD% across menstrual cycle, whereas brachial artery diameter was significantly more decreased in the luteal phase (P=0.013) than in the follicular phase.

Conclusion: We observed that the circulating ADMA concentration varies across the menstrual cycle in young women not using OCs, and women on OCs displayed significantly lower circulating ADMA concentrations than non-OC users, though this was not the case with POP contraception.