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

Abstract

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 1 month of leuprolide, which suppresses LH.

Setting: Clinical research center of an academic hospital.

Patient(s): Nine lean women (body mass index <or=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 micromol/kg.min) was similar to lean control subjects (52.9 micromol/kg.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.

FIGURE 1

Selected laboratory results at baseline and after treatment with diazoxide and leuprolide acetate in lean control (solid bars; n = 17) and lean PCOS (clear bars; n = 9) women. Results are presented as mean with SEM. To convert values for total T to nmol/L, multiply by 0.0347; for SHBG to nmol/L, multiply by 34.7; for free T to pmol/L, multiply by 34.7; and for androstenedione to nmol/L, multiply by 3.492; and for glucose to mmol/L, multiply by 0.0556. Free T was calculated by the method of Sodergard et al. (15). The normal ranges for ovulatory women are: total T, 20–80 ng/dL; SHBG, 0.6–3.0 μg/dL; free T, <1.4 ng/dL; androstenedione, 0.7–3.1 μg/L; LH, 0.5–9.8; and fasting glucose, 60–110 mg/dL. *P≤ .05 vs. control at baseline (by two-tailed paired t test); †P≤ .05 vs. baseline (by two-tailed paired t-test); ‡P≤ .05 vs. diazoxide (by two-tailed paired t test).