Metabolic Syndrome in PCOS: Precursors and Interventions

Condition(s) targeted: Polycystic Ovary Syndrome; Metabolic Syndrome

Intervention: Metformin (Drug); flutamide (Drug); drospirenone (Drug); placebo (Other)

Phase: N/A

Status: Recruiting

Sponsored by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Official(s) and/or principal investigator(s):
Andrea Dunaif, MD, Principal Investigator, Affiliation: Northwestern University

Overall contact:
Andrea Dunaif, MD, Phone: 312-503-2902, Email: a-dunaif@northwestern.edu

The purpose of this study is to determine whether lowering insulin levels using a medication called metformin, and blocking the action of male hormones with the medication flutamide wil decrease central body fat, improve cholesterol levels or affect sugar handling in women with PCOS (Polycystic ovary syndrome) The effects of these medications will be compared to the effects of the oral contraceptive pill (OCP), Yasmin.

Official title: Metabolic Syndrome in PCOS: Precursors and Interventions

Study design: Other, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Comparison of flutamide and metformin alone and in combination on cardiovascular disease risk factors after six months.

Secondary outcome: Predictors of response such as baseline androgen levels, FFA levels, insulin sensitivity and genotype.

Detailed description: Polycystic ovary syndrome (PCOS) is one of the most common conditions of young women, and it is frequently associated with insulin resistance or metabolic syndrome (MBS). In addition, affected women have significantly elevated mean LDL levels and an increased prevalence of at risk LDL levels, independent of obesity. There is a genetic susceptibility to PCOS and we have identified a major susceptibility gene or genetic element on chromosome 19p3. 2 near the insulin receptor gene that is linked and associated with the reproductive phenotype of hyperandrogenemia. We have mapped the location of this variant (allele 8[A8]D19S884)to an allele a dinucleotide repeat in intron 55 of the fibrillin 3 gene. We are directly testing the role of androgens in the metabolic abnormalities in PCOS by examining the impact of androgen receptor blockade, alone and in combination with insulin sensitization, on visceral adiposity and circulating LDL levels. Further, we will determine whether A8 is associated with differential responses to this intervention. We will use the pure antiandrogen, flutamide, and the insulin-sensitizing agent, metformin. In short term studies, OCP(oral contraceptive pill) decreased insulin sensitivity in women with PCOS. We have included a standard therapy arm with diet and the OCP, Yasmin, order to assess its impact on metabolic endpoints concurrently with the othe interventions so that the data will be directly comparable.

Minimum age: 18 Years. Maximum age: 35 Years. Gender(s): Female.

Criteria:

Inclusion Criteria:

- 6 periods or fewer per year

- Overweight

- All ethnicities

Exclusion Criteria:

- Diabetes

- Heart Disease

- Chronic illness

- Regular Smokers

- Current use of Birth Control Pills, Patch, Ring, Depo

Andrea Dunaif, MD, Phone: 312-503-2902, Email: a-dunaif@northwestern.edu

Northwestern Memorial Hospital, Chicago, Illinois 60611, United States; Recruiting
Andrea Dunaif, MD, Principal Investigator

Related publications:

Diamanti-Kandarakis E, Mitrakou A, Raptis S, Tolis G, Duleba AJ. The effect of a pure antiandrogen receptor blocker, flutamide, on the lipid profile in the polycystic ovary syndrome. J Clin Endocrinol Metab. 1998 Aug;83(8):2699-705.

Gambineri A, Patton L, Vaccina A, Cacciari M, Morselli-Labate AM, Cavazza C, Pagotto U, Pasquali R. Treatment with flutamide, metformin, and their combination added to a hypocaloric diet in overweight-obese women with polycystic ovary syndrome: a randomized, 12-month, placebo-controlled study. J Clin Endocrinol Metab. 2006 Oct;91(10):3970-80. Epub 2006 Jul 25.

Gambineri A, Pelusi C, Genghini S, Morselli-Labate AM, Cacciari M, Pagotto U, Pasquali R. Effect of flutamide and metformin administered alone or in combination in dieting obese women with polycystic ovary syndrome. Clin Endocrinol (Oxf). 2004 Feb;60(2):241-9.

Urbanek M, Sam S, Legro RS, Dunaif A. Identification of a polycystic ovary syndrome susceptibility variant in fibrillin-3 and association with a metabolic phenotype. J Clin Endocrinol Metab. 2007 Nov;92(11):4191-8. Epub 2007 Sep 4.

Starting date: July 2006
Ending date: July 2011
Last updated: July 7, 2009