Asymmetrical dimethylarginine, inflammatory and metabolic parameters in women with polycystic ovary syndrome before and after metformin treatment.
BACKGROUND
Insulin resistance plays a significant role in the pathogenesis of the polycystic ovary syndrome (PCOS) and represents a link to the unfavorable cardiovascular risk profile frequently found in affected patients. The endogenous nitric oxide synthase inhibitor asymmetrical dimethyl-L-arginine (ADMA) is associated with atherosclerosis and represents an independent marker for cardiovascular morbidity and mortality.


OBJECTIVE
We investigated ADMA levels among other cardiovascular, metabolic, and hormonal parameters in women with PCOS and the effects of metformin treatment on these parameters.


METHODS
A cross-sectional study and clinical trial were performed.


METHODS
Women with PCOS (n = 83) compared with a control group of healthy women (n = 39) were studied.


METHODS
In a subgroup of patients with PCOS (n = 21), the effect of metformin was assessed after 6 months of treatment.


METHODS
ADMA, intima media thickness (IMT), metabolic and hormonal parameters, and markers of inflammation were investigated.


RESULTS
ADMA levels were significantly higher in the PCOS group compared with controls (0.57 +/- 0.15 vs. 0.50 +/- 0.11; P = 0.024). Androgens, C-reactive protein, fasting C-peptide, area under the curve (AUC) insulin, AUC glucose, homeostatic assessment of insulin resistance, fasting insulin, glycosylated hemoglobin, cholesterol, low-density lipoprotein cholesterol, triglycerides, and IMT were significantly higher in women with PCOS compared with controls. In PCOS patients ADMA was found to be positively correlated with body mass index (BMI), waist to hip ratio, parameters of insulin sensitivity, hyperandrogenemia (free testosterone, free androgen index), and IMT. Treatment with metformin ameliorated hyperandrogenemia and decreased ADMA levels (0.53 +/- 0.06 vs. 0.46 +/- 0.09, P = 0.013). Decrease in ADMA levels subsequent to metformin treatment did not correlate with change in BMI or metabolic parameters.


CONCLUSIONS
ADMA amd parameters of insulin sensitivity are elevated in women with PCOS and the degree of insulin resistance confers the greatest influence on ADMA level. Metformin treatment led to improvement of hormonal and metabolic parameters and decreased ADMA levels possibly independent of BMI and metabolic changes.
Heutling
Dennis
D
Department of Endocrinology and Metabolism, Otto-von-Guericke-University, D-39120 Magdeburg, Germany.
Schulz
Hasmik
H
Nickel
Ingrid
I
Kleinstein
Juergen
J
Kaltwasser
Petra
P
Westphal
Sabine
S
Mittermayer
Friedrich
F
Wolzt
Michael
M
Krzyzanowska
Katarzyna
K
Randeva
Harpal
H
Schernthaner
Guntram
G
Lehnert
Hendrik
H
D000328:Adult; D000728:Androgens / Q000097:blood; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D008687:Metformin / Q000627:therapeutic use*; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000188:drug therapy*; D018709:Statistics, Nonparametric; D014280:Triglycerides / Q000097:blood; D049629:Waist-Hip Ratio
D000728:Androgens; D001120:Arginine; D001786:Blood Glucose; D002097:C-Reactive Protein; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D014280:Triglycerides; C018524:N,N-dimethylarginine