Metabolic Syndrome in PCOS: Precursors and Interventions

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.

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