EFFECTS OF A REDUCTION IN CIRCULATING INSULIN BY METFORMIN ON SERUM DEHYDROEPIANDROSTERONE-SULFATE IN NONDIABETIC MEN

Evidence suggests that hyperinsulinemic insulin resistance may reduce serum levels of the adrenal steroid dehydroepiandrosterone (DHEA) sulf ate in humans. This study was conducted to assess the influence of phy siological concentrations of insulin on serum adrenal steroid levels b y lowering circulating insulin in nondiabetic men through the administ ration of the biguanide metformin. A total of 28 nondiabetic men were studied. The study group consisted of 16 obese and hypertensive men, a nd the control group of 12 nonobese and normotensive men. The men were studied at baseline and after the oral administration of 500 mg metfo rmin, 3 times daily, for 21 days. Metformin administration resulted in significant reductions in serum insulin levels and concurrent increas es in serum DHEA sulfate levels in both groups of men. The mean fastin g serum DHEA sulfate concentration rose by 48% in the obese hypertensi ve men (from 5.9 +/- 0.8 to 8.7 +/- 0.7 mu mol/L; P < 0.02) and by 80% in the nonobese normotensive men (from 3.5 +/- 0.5 to 6.3 +/- 0.9 mu mol/L; P < 0.05). When the results from both groups were combined, cha nges in serum DHEA sulfate levels (i.e. day 21 value minus day 0 value ) correlated positively with baseline fasting serum insulin levels (r = 0.44; P = 0.02; n = 28). Moreover, changes in fasting serum DHEA sul fate levels correlated inversely with changes in fasting serum insulin levels (r = -0.38; P < 0.05; n = 28). These findings lend further cre dence to the idea that insulin acts as a physiological regulator of DH EA sulfate metabolism and lowers circulating DHEA sulfate concentratio ns in men.