Endothelial function and insulin resistance in polycystic ovary syndrome: the effects of medical therapy.
OBJECTIVE
To assess the interaction between insulin resistance and endothelial function and the optimal treatment strategy addressing cardiovascular risk in polycystic ovary syndrome.


METHODS
Randomized controlled trial.


METHODS
Controlled clinical study.


METHODS
Overweight age- and body mass index-matched women with polycystic ovary syndrome.


METHODS
Six months metformin (1 g two times per day, n = 36) or oral contraceptive pill (OCP) (35 microg ethinyl E(2)-2 mg cytoproterone acetate, n = 30).


METHODS
Fasting and oral glucose tolerance test glucose and insulin levels, endothelial function (flow-mediated dilation, asymmetric dimethylarginine, plasminogen activator inhibitor-1, von Willebrand factor), inflammatory markers (high-sensitivity C-reactive protein), lipids, and hyperandrogenism.


RESULTS
The OCP increased levels of glucose and insulin on oral glucose tolerance test, high-sensitivity C-reactive protein, triglycerides, and sex-hormone binding globulin and decreased levels of low-density lipoprotein cholesterol and T. Metformin decreased levels of fasting insulin, oral glucose tolerance test insulin, high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. Flow-mediated dilation increased only with metformin (+2.2% +/- 4.8%), whereas asymmetric dimethylarginine decreased equivalently for OCP and metformin (-0.3 +/- 0.1 vs. -0.1 +/- 0.1 mmol/L). Greater decreases in plasminogen activator inhibitor-1 occurred for the OCP than for metformin (-1.8 +/- 1.6 vs. -0.7 +/- 1.7 U/mL).


CONCLUSIONS
In polycystic ovary syndrome, metformin improves insulin resistance, inflammatory markers, and endothelial function. The OCP worsens insulin resistance and glucose homeostasis, inflammatory markers, and triglycerides and has neutral or positive endothelial effects. The effect of the OCP on cardiovascular risk in polycystic ovary syndrome is unclear.
Teede
Helena J
HJ
The Jean Hailes Foundation for Women's Health, Monash Institute of Health Services Research, Monash University, Melbourne, Victoria, Australia.
Meyer
Caroline
C
Hutchison
Samantha K
SK
Zoungas
Sophia
S
McGrath
Barry P
BP
Moran
Lisa J
LJ
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects / Q000627:therapeutic use*; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D017373:Cyproterone Acetate / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004997:Ethinyl Estradiol / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D017588:Hyperandrogenism / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008687:Metformin / Q000627:therapeutic use*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects; D014841:von Willebrand Factor / Q000378:metabolism
D015415:Biomarkers; D001786:Blood Glucose; D003277:Contraceptives, Oral, Combined; D003278:Contraceptives, Oral, Hormonal; D007004:Hypoglycemic Agents; D018836:Inflammation Mediators; D007328:Insulin; D008055:Lipids; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D012738:Sex Hormone-Binding Globulin; D014841:von Willebrand Factor; D013739:Testosterone; D004997:Ethinyl Estradiol; D017373:Cyproterone Acetate; C018524:N,N-dimethylarginine; D002097:C-Reactive Protein; D008687:Metformin; D001120:Arginine