Effects of Flutamide on Insulin and Glucose Metabolism in Women With Polycystic Ovary Syndrome (PCOS)
PCOS is the major cause of infertility in the United States. Many women with PCOS demonstrate insulin resistance and a compensatory hyperinsulinemia.This is due to both an intrinsic form of insulin resistance unique to PCOS and, in many cases, acquired insulin resistance due to obesity. The importance of this observation lies in the fact that hyperinsulinemia appears to play an important pathogenetic role in the hyperandrogenism and anovulation of both obese and lean women with PCOS.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Health Services Research
|Official Title:||Determination if Pharmacologic Blockade of Androgen Action Decreases Renal Clearance of DCI, Increases the Circulating Concentration of DCI, and Enhances Insulin-Stimulated Release of the DCI-IPG Mediator in Obese Women With PCOS|
- DCI-IPG measurements in blood and urine [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Measurement of sex steroids [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||July 2008|
|Study Completion Date:||February 2012|
|Primary Completion Date:||February 2012 (Final data collection date for primary outcome measure)|
250 mg twice daily for 4 weeks
Placebo Comparator: 2
control to arm 1
Placebo twice daily for 4 weeks
Hyperinsulinemia stimulates ovarian production of androgens, especially testosterone, in PCOS. Therefore, it is theoretically possible that testosterone increases uClDCI in PCOS, and that this serves as the explanation for the correlation between uClDCI and insulin sensitivity. While we regard this possibility as unlikely, it is important that it be tested. To accomplish this, we will assess obese (BMI >30 kg/m2) women with and without PCOS at baseline, and again after 4 weeks of androgen action blockade with the drug flutamide. Flutamide is an antiandrogen that works by blocking the binding of androgens to the androgen receptor.
We will determine if this pharmacologic blockade i) decreases the renal clearance of DCI, ii) increases the circulating concentration of DCi, and iii) enhances the insulin-stimulated release of the DCI-IPG mediator during an OGTT.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00729560
|United States, Virginia|
|Virginia Commonwealth University General Clinical Research Center|
|Richmond, Virginia, United States, 23298|
|Principal Investigator:||John E. Nestler, M.D.||Virginia Commonwealth University|