Troglitazone decreases adrenal androgen levels in women with polycystic ovary syndrome.
OBJECTIVE
To determine whether amelioration of insulin resistance in polycystic ovary syndrome (PCOS) with the insulin sensitizer troglitazone (TGZ) decreases circulating adrenal androgens (AAs), as reflected by DHEAS levels.


METHODS
Prospective, randomized, double-blind clinical trial.


METHODS
Multicenter study.


METHODS
Three-hundred five women with PCOS.


METHODS
Subjects were randomly assigned to receive either placebo (PBO; n = 73) or TGZ in doses of 150 mg/day (TGZ-150; n = 78), 300 mg/day (TGZ-300; n = 77), or 600 mg/day (TGZ-600; n = 77) for 20 weeks. Blood was sampled before (week 0) and at week 20 of treatment.


METHODS
DHEAS, insulin, and glucose levels were determined in the blood samples.


RESULTS
There were no differences in age, body mass, or racial composition among the groups. Our results indicate that basal insulin declined in a dose-related fashion. Likewise, TGZ administration caused a dose-related decrease in DHEAS levels. To detect extreme effects, we subsequently subdivided patients receiving PBO or TGZ-600 into tertiles according to initial DHEAS levels. Patients receiving PBO in the lowest (n = 27) and highest (n = 22) DHEAS tertiles experienced a 16.8% +/- 62.0% and a -11.1% +/- 17.4% change in DHEAS levels during the study, respectively. Alternatively, patients with PCOS receiving TGZ-600 in both the lowest (n = 29) and the highest (n = 23) DHEAS tertiles experienced a drop in DHEAS levels (-18.7% +/- 27.2% and -26.4% +/- 17.2%, respectively), a significant difference from PBO.


CONCLUSIONS
In conclusion, improving the insulin resistance-related hyperinsulinemia of PCOS with TGZ results in a decrease in DHEAS levels, regardless of initial DHEAS level. Whether the observed suppression is the direct result of decreased insulin levels or whether it reflects other direct and indirect effects of TGZ remains to be determined.
Azziz
Ricardo
R
Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama, USA. azzizr@cshs.org
Ehrmann
David A
DA
Legro
Richard S
RS
Fereshetian
Anita G
AG
O'Keefe
Mary
M
Ghazzi
Mahmoud N
MN
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology* / Q000627:therapeutic use; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D017588:Hyperandrogenism / Q000097:blood / Q000188:drug therapy; D006946:Hyperinsulinism / Q000097:blood / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000188:drug therapy; D011446:Prospective Studies; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D045162:Thiazolidinediones; D000077288:Troglitazone
D001786:Blood Glucose; D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D019314:Dehydroepiandrosterone Sulfate; D000077288:Troglitazone