A randomized placebo-controlled study on the effects of pioglitazone on cortisol metabolism in polycystic ovary syndrome.
OBJECTIVE
To investigate possible effects of insulin-sensitizing treatment on cortisol metabolism in insulin-resistant patients with polycystic ovary syndrome (PCOS).


METHODS
Randomized placebo-controlled study.


METHODS
Academic tertiary care medical center.


METHODS
Thirty insulin-resistant PCOS patients.


METHODS
Sixteen weeks of pioglitazone (30 mg/day) or placebo treatment.


METHODS
Twenty-four-hour 20 min integrated blood sampling for measurement of cortisol and 24 h urinary excretion of steroid metabolites. Relative 5alpha-reductase activity was evaluated by allotetrahydrocortisol (alloTHF)/THF and androsterone/etiocholanolone (A/E) ratios. Delta values denoted changes during the treatment period (16 weeks--basal). Pyridostigmine growth hormone (GH) stimulation tests were performed, and testosterone (T), dihydrotestosterone (DHT), DHEA, DHEAS, adiponectin, and insulin-like growth factor I (IGF-I) were measured before and after intervention.


RESULTS
Insulin sensitivity, GH, adiponectin, and IGF-I significantly increased during pioglitazone treatment, whereas alloTHF/THF levels significantly decreased. Delta alloTHF/THF levels inversely correlated with Delta adiponectin levels. Delta A/E ratio inversely correlated with Delta IGF-I and Delta peak GH during GH stimulation tests. No significant changes were measured in T, DHT, DHEA, DHEAS, 24 h mean cortisol, or urinary excretion of steroid metabolites.


CONCLUSIONS
Pioglitazone decreased relative 5alpha-reductase activity, whereas no significant changes were measured in cortisol levels or urinary cortisol excretion.
Glintborg
Dorte
D
Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark. dorte.glintborg@dadlnet.dk
Hermann
Anne Pernille
AP
Hagen
Claus
C
Jensen
Lars Thorbjørn
LT
Frystyk
Jan
J
Bennett
Paul
P
Flyvbjerg
Allan
A
Andersen
Marianne
M
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D052242:Adiponectin / Q000097:blood; D000738:Androsterone / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects; D003718:Denmark; D005043:Etiocholanolone / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism* / Q000652:urine; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D000077205:Pioglitazone; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D013760:Tetrahydrocortisol / Q000031:analogs & derivatives / Q000378:metabolism; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
C499918:ADIPOQ protein, human; D052242:Adiponectin; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D019382:Human Growth Hormone; C006461:allotetrahydrocortisol; D013739:Testosterone; D013760:Tetrahydrocortisol; D005043:Etiocholanolone; D000738:Androsterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D006854:Hydrocortisone; D000077205:Pioglitazone