Effect of pioglitazone on glucose metabolism and luteinizing hormone secretion in women with polycystic ovary syndrome.
OBJECTIVE
To thoroughly examine the mechanisms for insulin resistance in polycystic ovary syndrome (PCOS) and to evaluate the effects of pioglitazone treatment on insulin resistance, beta-cell function, LH secretion, and glucose metabolism.


METHODS
Randomized, blinded, placebo-controlled study.


METHODS
Outpatient clinic, at a university hospital in Denmark.


METHODS
Thirty obese women with PCOS and 14 weight-matched healthy females.


METHODS
Sixteen weeks of blinded treatment with pioglitazone (30 mg/d) or placebo.


METHODS
Fasting blood samples, 24-hour 20-minute integrated blood sampling (LH, insulin, and C-peptide), euglycemic hyperinsulinemic clamps including 3-(3)H glucose, and indirect calorimetry were performed before and after the intervention period.


RESULTS
Patients with PCOS had significantly lower insulin sensitivity compared with controls, including significantly decreased insulin-stimulated oxidative and nonoxidative glucose metabolism. Pioglitazone treatment resulted in significantly lower levels of fasting insulin and significantly higher insulin sensitivity, increased insulin-stimulated glucose oxidation, and increased insulin-stimulated inhibition of lipid oxidation. During 24-hour blood sampling, significantly lower area under-the-curve insulin and lower median insulin levels were observed. Secretion profiles of LH and E(2) and T levels did not change significantly.


CONCLUSIONS
Insulin resistance in PCOS was characterized by hyperinsulinemia, impaired insulin-stimulated oxidative and nonoxidative glucose metabolism, which was partly reversed by pioglitazone treatment.
Glintborg
Dorte
D
Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark. dorte.glintborg@dadlnet.dk
Hermann
Anne Pernille
AP
Andersen
Marianne
M
Hagen
Claus
C
Beck-Nielsen
Henning
H
Veldhuis
Johannes D
JD
Henriksen
Jan Erik
JE
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D004311:Double-Blind Method; D005215:Fasting / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D006728:Hormones / Q000097:blood; D006801:Humans; D006946:Hyperinsulinism / Q000209:etiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism*; D008597:Menstrual Cycle / Q000187:drug effects; D010084:Oxidation-Reduction; D000077205:Pioglitazone; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D045162:Thiazolidinediones / Q000627:therapeutic use*
D001786:Blood Glucose; D006728:Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D007986:Luteinizing Hormone; D000077205:Pioglitazone