Pioglitazone reduces the adrenal androgen response to corticotropin-releasing factor without changes in ACTH release in hyperinsulinemic women with polycystic ovary syndrome.
OBJECTIVE
The hypothalamic-pituitary-adrenal (HPA) axis seems to hyperfunction at both central and peripheral levels in polycystic ovary syndrome (PCOS). Hyperinsulinemia is involved in the adrenal hyper-responsiveness to ACTH. The present study was performed to investigate the role of insulin in the derangement of the hypothalamic-pituitary compartment of the HPA axis in PCOS.


METHODS
Prospective clinical study.


METHODS
Academic research center.


METHODS
Fifteen hyperinsulinemic PCOS women.


METHODS
Hormonal and lipid assays, oral glucose tolerance test, and corticotropin-releasing factor (1 microg/kg CRF) test before and after 4 months of treatment with the insulin sensitizer pioglitazone (30 mg/day).


METHODS
Glycemic and insulinemic response to glucose load; pituitary and adrenal response to CRF.


RESULTS
We observed a significant reduction in insulin secretion after therapy. Pioglitazone administration did not modify ACTH and cortisol response to CRF. A significant reduction in the adrenal CRF-induced secretion of androstenedione (A) (area under the curve [AUC] 202.76 +/- 78.68 ng/mL x 90 minutes to 147.05 +/- 52.06 ng/mL x 90 minutes) and 17OH-progesterone (AUC 152.92 +/- 59.56 ng/mL x 90 minutes to 117.10 +/- 63.25 ng/mL x 90 minutes') occurred after treatment. A trace response to CRF was observed for DHEAS and testosterone both before and after pioglitazone.


CONCLUSIONS
In PCOS subjects, insulin may enhance adrenal steroidogenesis by acting directly on the peripheral gland, with no significant effects on the pituitary response to CRF stimulation.
Romualdi
Daniela
D
Department of Obstetrics and Gynaecology, Università Cattolica del Sacro Cuore, Rome, Italy.
Giuliani
Maddalena
M
Draisci
Gaetano
G
Costantini
Barbara
B
Cristello
Francesca
F
Lanzone
Antonio
A
Guido
Maurizio
M
D000293:Adolescent; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000328:Adult; D000728:Androgens / Q000097:blood / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood* / Q000188:drug therapy; D000077205:Pioglitazone; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D011446:Prospective Studies; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*
D000728:Androgens; D045162:Thiazolidinediones; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D000077205:Pioglitazone