Twenty-eight women (mean age, 50.2 years) with hypoadrenalism due to Addison's disease (71%) or bilateral adrenalectomy for Cushing's disease (29%) were randomly assigned to receive, in double-blind fashion, 50 mg/day of DHEA or placebo for 12 weeks. Compared with placebo, DHEA significantly increased insulin sensitivity, as determined using a hyperinsulinemic-euglycemic clamp (p < 0.05), and significantly decreased the mean fasting plasma insulin concentration (p = 0.005).

Comment: These results indicate that supplementation with 50 mg/day of DHEA for 12 weeks significantly increased insulin sensitivity in women with adrenal insufficiency. In an earlier study, administration of 50 mg/day of DHEA reduced abdominal fat and insulin resistance in elderly men and women (JAMA 2004;292:2243-2248). Observational studies have shown that the normal age-related decline in DHEA levels may play a role in the development of age-related insulin resistance. Taken together, these studies suggest that supplementation with physiological doses of DHEA would improve glucose metabolism in people with sub-optimal DHEA levels. However, DHEA treatment may not be advisable for everyone with insulin resistance, only those with evidence of DHEA deficiency. For example, many women with polycystic ovary syndrome have both insulin resistance and elevated blood levels of DHEA. I have found that the serum concentration of DHEA-sulfate is a reasonably good indicator of a person's DHEA status. Serum DHEA may be even more reliable, but DHEA is present in such small concentrations in the blood that the laboratory measurement may be prone to error.

Dhatariya K, et al. Effect of dehydroepiandrosterone replacement on insulin sensitivity and lipids in hypoadrenal women. Diabetes 2005;54:765-769.