Effect of pioglitazone treatment on the adrenal androgen response to corticotrophin in obese patients with polycystic ovary syndrome

Background: To investigate the effect of pioglitazone on adrenal steroidogenesis in polycystic ovary syndrome (PCOS), we studied 11 obese (two with BMI>25 kg/m(2); nine with BMI>27 kg/m(2)) PCOS women before and after 6 months of treatment at a dose of 45 mg/day. Methods: During the early follicular phase, ultrasonography and hormonal assays were performed. On separate days, all women underwent an oral glucose tolerance test (OGTT), a euglycaemic hyperinsulinaemic clamp and an adrenocorticotrophin hormone (ACTH) test. The same protocol was repeated after therapy. Results: Pioglitazone treatment significantly reduced the insulin response to OGTT and improved the insulin sensitivity indices (P<0.01 and P=0.03 respectively). A significant decrease was found in LH (P<0.05) and androstenedione (P<0.01) levels after therapy, whereas the other hormonal parameters improved but not significantly. Pioglitazone administration reduced the response of 17alpha-hydroxyprogesterone (17OHP) and androstenedione to ACTH (P<0.01 and P<0.02 respectively), most likely through an inhibition of cytocrome P450. The same treatment was able to rebalance the relative activity of 17,20-lyase, as documented by an increase in the androstenedione:17OHP ratio (P<0.05) after ACTH stimulation. Conclusions(:) Our data support the contention that insulin enhances ACTH-stimulated steroidogenesis, while inducing a relative impairment of 17,20-lyase activity. Whether the beneficial effects of pioglitazone on this imbalance could be related to the ameliorated glyco-insulinaemic metabolism or to a direct effect on the adrenal glands remains to be determined.