Effect of dehydroepiandrosterone replacement on insulin sensitivity and lipids in hypoadrenal women

DHEA (dehydroepiandrosterone) replacement is not part of the current standard of care in hypoadrenal subjects. Animal studies have shown that DHEA administration prevents diabetes. To determine the physiological effect of DHEA replacement on insulin sensitivity in adrenal-deficient women, we performed a single-center, randomized, double-blind, placebo-controlled, crossover study in 28 hypoadrenal women (mean age 50.2 +/- 2.87 years) who received a single 50-mg dose of DHEA daily or placebo. After 12 weeks, insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp. DHEA replacement significantly increased DHEA-S (sulfated ester of DHEA), bioavailable testosterone, and androstenedione and reduced sex hormone-binding globulin levels. Fasting plasma insulin and glucagon were lower with DHEA (42 +/- 4.94 vs. 53 +/- 6.58 pmol/l [P = 0.005] and 178 +/- 11.32 vs. 195.04 +/- 15 pmol/l [P = 0.02], respectively). The average amount of glucose needed to maintain similar blood glucose levels while infusing the same insulin dosages was higher during DHEA administration (358 +/- 24.7 vs. 320 +/- 24.6 mg/min; P < 0.05), whereas endogenous glucose production was similar. DHEA also reduced total cholesterol (P < 0.005), triglycerides (P < 0.011), LDL cholesterol (P < 0.05), and HDL cholesterol (P < 0.005). In conclusion, replacement therapy with 50 mg of DHEA for 12 weeks significantly increased insulin sensitivity in hypoadrenal women, thereby suggesting that DHEA replacement could have a potential impact in preventing type 2 diabetes.