Effects of Flutamide on Insulin and Glucose Metabolism in Women With Polycystic Ovary Syndrome

Condition(s) targeted: Polycystic Ovary Syndrome

Intervention: Flutamide (Drug); Placebo (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Official(s) and/or principal investigator(s):
John E. Nestler, M.D., Principal Investigator, Affiliation: Virginia Commonwealth University

Overall contact:
Terre Y. Williams, Phone: (804) 828-2663, Email: tywillia@vcu.edu

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.

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

Study design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Health Services Research

Primary outcome: DCI-IPG measurements in blood and urine

Secondary outcome: Measurement of sex steroids

Detailed description: 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.

Minimum age: 18 Years. Maximum age: 40 Years. Gender(s): Female.

Criteria:

Inclusion Criteria:

(1) Obese (BMI≥30 kg/m2) women with PCOS between 18-40 years of age: i) oligomenorrhea (8 menstrual periods annually), ii) biochemical hyperandrogenemia (elevated total or free testosterone), iii) normal thyroid function tests and serum prolactin, and iv) exclusion of 21α-hydroxylase deficiency by a fasting 17α-hydroxyprogesterone <200 ng/dl. 48, (2) acceptable health on the basis of interview, medical history, physical examination, and laboratory tests (CBC, SMA20, urinalysis, serum BhCG). (3) Signed, witnessed informed consent. (4) Ability to comply with study requirements.

Exclusion Criteria:

(1) Diabetes mellitus by fasting glucose or OGTT, or clinically significant pulmonary, cardiac, renal, hepatic, neurologic, psychiatric, infectious, neoplastic and malignant disease (other than non-melanoma skin cancer). (2) Current use of oral contraceptives. (3) Documented or suspected recent (within one year) history of drug abuse or alcoholism. (4) Ingestion of any investigational drug within two months prior to study onset.

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Terre Y. Williams, Phone: (804) 828-2663, Email: tywillia@vcu.edu

Virginia Commonwealth University General Clinical Research Center, Richmond, Virginia 23298, United States; Recruiting
Terre Y. Williams, Phone: 804-828-2663, Email: tywillia@vcu.edu
Manar T. Nazmy, Phone: (804) 827-0171, Email: mtnazmy@vcu.edu
John E. Nestler, M.D., Principal Investigator

Starting date: July 2008
Last updated: May 18, 2011