Abstract

Background: DHEA stimulates endothelial nitric oxide (NO) production in vitro and its prolonged use in humans improves vascular function. It is believed that this effect is mediated by metabolism of DHEA to androgens and estrogens. We hypothesized that DHEA action is mediated by a rapid, receptor-ependent, endothelial NO production pathway. We tested this hypothesis by studying the acute effect of a single oral dose of DHEA on vascular function in postmenopausal diabetic women.

Design and Methods: This was a double blind, randomized, placebo controlled, cross-over study. Nine postmenopausal women with type 2 diabetes and 5 age- and weight- matched controls received 50 mg of DHEA or placebo in a random order one week apart. We examined forearm resistance vessel responses to intra-arterial nitroprusside, acetylcholine and verapamil.

Results: There was no difference in baseline characteristics and steroid hormone levels between the groups. Following administration of DHEA, steroid hormone concentrations increased in both diabetics and controls indicating adequate absorption and metabolism of DHEA. Prior to administration of arterial vasodilators, there was no difference in baseline forearm blood flow between diabetics and controls and within each group in response to DHEA versus placebo. There was also no difference in the vasodilator-induced increment in blood flow between diabetics and controls and within each group in response to DHEA versus placebo.

Conclusions: In postmenopausal women with diabetes, DHEA did not have any acute effect on basal or vasodilator stimulated forearm blood flow, despite evidence of systemic absorption and adequate vascular responses to endothelium and non-endothelium dependent vasodilators.

Keywords: vasodilator, endothelium, nitric oxide, postmenopausal