Impact of glycemic variations on the regulation of androgen metabolism in obese women with polycystic ovary syndrome

Objective: To assess the influence of alterations in glucose concentrations on androgen levels in patients with polycystic ovary syndrome (PCOS) and in healthy controls. Design: Prospective, controlled study. Setting: Tertiary care center. Patient(s): Seven patients with PCOS and 20 healthy controls. Intervention(s): Hyperinsulinemic glucose clamp study with stepwise reduction of the plasma glucose level from hyperglycemia to hypoglycemia. Main Outcome Measure(s): Concentrations of insulin, C-peptide, cortisol, T, androstenedione, 17-hydroxyprogesterone, DHEA, and DHEAS during hyperglycemia, euglycemia, and hypoglycemia. Result(s): Total T levels and the free androgen index were significantly higher in the PCOS group at baseline and throughout the clamp. The levels of T, androstenedione, DHEAS, and 17-hydroxyprogesterone were not influenced by short-term changes of plasma glucose concentrations in both groups. However, hypoglycemia led to a significant increase in DHEA levels in PCOS patients as well as in controls. Cortisol levels were not increased during hypoglycemia in either group. Conclusion(s): In contrast to men, androgen levels are not influenced by short-term changes of plasma glucose levels in PCOS patients and in healthy women. However, DHEA concentrations increase with decreasing glucose levels independently from an activation of the hypothalamic-pituitary-adrenal axis. This supports a gender difference regarding the counterregulatory hormone response to hypoglycemia.