Differential effects of oral glucose-mediated versus intravenous hyperinsulinemia on circulating androgen levels in women

Abstract

To determine whether transient endogenous or continuous exogenous hyperinsulinemia produced different changes in circulating gonadal steroid levels because insulin is a putative regulator of gonadal steroid secretion in polycystic ovarian syndrome (PCOS). An oral glucose tolerance test (OGTT) and a 2-hour euglycemic clamp (+100 microU/mL [718 pmol/L] steady-state insulin levels) were performed in obese patients with PCOS (n = 7) in nonobese patients with PCOS (n = 5), and in age- and weight-matched ovulating normal women (obese normal n = 7, nonobese normal n = 6). Despite increased insulin levels, the levels of T and androstenedione (A) decreased in three of the four groups during the OGTT (nonobese normal women showed a slight increase in T during the OGTT). In contrast, the continuous 2-hour insulin infusion resulted in increased androgen levels. When all four groups were pooled, the difference in the changes in A levels between the two tests was significant, and the difference in T levels between the two tests approached significance. Transient physiological hyperinsulinemia produced by an oral glucose load was associated with a decrease rather than an increase in circulating androgen levels. The effects on circulating androgen levels of oral glucose-mediated increases in insulin levels were significantly different from those of a continuous intravenous insulin infusion. Sustained hyperinsulinemia produced by exogenous insulin infusion appeared to be required to increase androgen levels in women; transient physiological increases in insulin levels after an oral glucose load were insufficient to produce hyperandrogenism. Postmeal hyperinsulinemia does not contribute to hyperandrogenism in women.