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 cytochrome 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.
Department of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Largo A.Gemelli 8, 00168 Roma, Italy. maurizioguido@libero.it
M
M
Guido
D
D
Romualdi
R
R
Suriano
M
M
Giuliani
B
B
Costantini
R
R
Apa
A
A
Lanzone
D019326:17-alpha-Hydroxyprogesterone / Q000378:metabolism; D000311:Adrenal Glands / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone; D000328:Adult; D000728:Androgens / Q000378:metabolism*; D000735:Androstenedione / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005951:Glucose Tolerance Test; D006728:Hormones / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007986:Luteinizing Hormone / Q000097:blood; D009765:Obesity / Q000150:complications*; D000077205:Pioglitazone; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D045162:Thiazolidinediones / Q000008:administration & dosage*
D000728:Androgens; D006728:Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000735:Androstenedione; D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D013254:Steroid 17-alpha-Hydroxylase; D000077205:Pioglitazone