Role of insulin in the hyperandrogenemia of lean women with polycystic ovary syndrome and normal insulin sensitivity

Objective: To determine the effect of reducing insulin secretion on hyperandrogenemia in lean normoinsulinemic women with polycystic ovary syndrome (PCOS) and normal metabolic insulin sensitivity. Design: Transversal assessment at baseline and prospective follow-up of lean PCOS group after 8 days of diazoxide, which reduces insulin secretion, and I month of leuprolide, which suppresses LH. Setting: Clinical research center of an academic hospital. Patient(s): Nine lean women (body mass index <= 25 kg/m(2)) with PCOS and normal insulin levels, as well as 17 lean healthy women. Intervention(s): Lean PCOS women were reassessed after 8 days of diazoxide and after 1 month of leuprolide, which suppresses LH. Main Outcome Measure(S): Androgen levels and insulin-stimulated glucose disposal (metabolic insulin sensitivity), determined by euglycemic-hyperinsulinemic clamp (M-value). Result(s): Mean M-value of lean PCOS women (48.5 mu mol/kg center dot min) was similar to lean control subjects (52.9 mu mol/kg center dot min). They also had comparable anthropometric measures, lipids, fibrinogen, and plasminogen activator inhibitor 1. The LH did not change significantly after diazoxide, but was almost suppressed after leuprolide in the PCOS group. Androstenedione decreased significantly after diazoxide and even more after leuprolide. However, free T significantly decreased only after diazoxide in lean PCOS women. Diazoxide also increased SHBG significantly in this group. Conclusion(s): In women with typical PCOS and normal insulin levels and metabolic insulin sensitivity, reducing insulin secretion significantly decreased androgen and increased SHBG levels. These results suggest that insulin contributes to hyperandrogenemia even in PCOS women with normal metabolic insulin sensitivity, which might be due to increased sensitivity of their androgenic insulin pathway.