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


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.


CONCLUSIONS
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.
Valtonen
Pirjo
P
Departments of Clinical Chemistry Obstetrics and Gynaecology, Kuopio University Hospital and University of Kuopio, FIN-70210 Kuopio, Finland.
Punnonen
Kari
K
Saarelainen
Heli
H
Heiskanen
Nonna
N
Raitakari
Olli T
OT
Juonala
Markus
M
Viikari
Jorma S A
JS
Alfthan
Georg
G
Kähönen
Mika
M
Laaksonen
Reijo
R
Lyyra-Laitinen
Tiina
T
Laitinen
Tomi
T
Heinonen
Seppo
S
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D050197:Atherosclerosis / Q000453:epidemiology* / Q000378:metabolism; D001916:Brachial Artery / Q000502:physiology; D002097:C-Reactive Protein / Q000378:metabolism; D003276:Contraceptives, Oral / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D004967:Estrogens / Q000627:therapeutic use; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008597:Menstrual Cycle / Q000378:metabolism*; D045167:Progesterone Congeners / Q000627:therapeutic use; D011446:Prospective Studies; D012307:Risk Factors; D014664:Vasodilation / Q000502:physiology; D055815:Young Adult
D003276:Contraceptives, Oral; D004967:Estrogens; D045167:Progesterone Congeners; C018524:N,N-dimethylarginine; D002097:C-Reactive Protein; D001120:Arginine; D003404:Creatinine