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).

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.

Key Words: PCOS, PPAR-γ, cortisol, steroid metabolites, adiponectin, insulin sensitivity, free fatty acids, growth hormone, IGF-I