Metabolic Syndrome in PCOS: Precursors and Interventions

• Comparison of flutamide and metformin alone and in combination on cardiovascular disease risk factors after six months. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  

• Predictors of response such as baseline androgen levels, FFA levels, insulin sensitivity and genotype. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  

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.