A randomized placebo-controlled study on the effects of pioglitazone on cortisol metabolism in polycystic ovary syndrome
Received 21 October 2007; received in revised form 31 December 2007; accepted 31 December 2007. published online 09 April 2008.
Objective
To investigate possible effects of insulin-sensitizing treatment on cortisol metabolism in insulin-resistant patients with polycystic ovary syndrome (PCOS).
Design
Randomized placebo-controlled study.
Setting
Academic tertiary care medical center.
Patient(s)
Thirty insulin-resistant PCOS patients.
Intervention(s)
Sixteen weeks of pioglitazone (30 mg/day) or placebo treatment.
Main Outcome Measure(s)
Twenty-four-hour 20 min integrated blood sampling for measurement of cortisol and 24 h urinary excretion of steroid metabolites. Relative 5α-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.
Result(s)
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 Δ adiponectin levels. Δ A/E ratio inversely correlated with Δ IGF-I and Δ 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.
Conclusion(s)
Pioglitazone decreased relative 5α-reductase activity, whereas no significant changes were measured in cortisol levels or urinary cortisol excretion.
Reprint requests: Dorte Glintborg, Odense University Hospital, Kløvervænget 6, Third floor, DK-5000 Odense, Denmark.
D.G. has nothing to disclose. A.P.H. has nothing to disclose. C.H. has nothing to disclose. L.T.J. has nothing to disclose. J.F. has nothing to disclose. P.B. has nothing to disclose. A.F. has nothing to disclose. M.A. has nothing to disclose.
Supported by Fonden for Lægevidenskabelig Forskning ved Fyns Amt, Jacob Madsen and Olga Madsen Foundation, Institute of Clinical Research, Odense University Hospital, A. P. Møller Foundation, Hans and Nora Buchard Foundation, K. A. Rohde Foundation, Aase and Ejnar Danielsen Foundation, Eva and Carl Adolf Holm Foundation, Dagmar Marshall Foundation, Danish Medical Association, A. J. Andersen Foundation, Novo Nordisk Foundation, Overlægerådet Odense University Hospital, Danish Diabetes Association, and Danish Medical Research Council.