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Effects of Dehydroepiandrosterone Replacement on Vascular Function in Primary and Secondary Adrenal Insufficiency: A Randomized Crossover Trial

Centre for Endocrine and Diabetes (S.P.L.R., N.A., H.B., M.F.S., M.L., D.A.R.) and Department of Primary Care and Public Health (R.N.), School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom

Address all correspondence and requests for reprints to: Dr. D. Aled Rees, Centre for Endocrine and Diabetes Sciences, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, United Kingdom. E-mail: reesda{at}cf.ac.uk.

Context: Patients with Addison’s disease and hypopituitarism have increased mortality, chiefly related to vascular disease. Both diseases are characterized by dehydroepiandrosterone (DHEA) deficiency, yet this is not usually corrected. It is unclear whether treatment of these conditions with DHEA improves cardiovascular risk.

Objective: The aim of the study was to evaluate the effects of DHEA on arterial stiffness and endothelial function in subjects with Addison’s disease and hypopituitarism.

Design and Intervention: Forty subjects (20 with Addison’s disease, 20 with panhypopituitarism) were assigned to consecutive 12-wk treatment periods of DHEA 50 mg or placebo in a randomized, double-blind, crossover design separated by an 8-wk washout.

Main Outcome Measures: Primary outcome parameters were measures of arterial stiffness [augmentation index, central blood pressure, brachial and aortic pulse wave velocity (PWV)] and endothelial function. Serum androgens, anthropometry, and metabolic biochemistry (lipids, homeostasis model of assessment for insulin resistance, high sensitivity C-reactive protein, adiponectin, plasminogen activator inhibitor-1) were also assessed.

Results: Despite normalization of DHEA sulfate, androstenedione, and testosterone (females), DHEA replacement did not affect augmentation index, aortic PWV, brachial PWV, central blood pressure, or endothelial function. DHEA did not affect any anthropometric or metabolic measures, apart from a small reduction in high-density lipoprotein cholesterol (–0.08 mmol/liter; P = 0.007; 95% confidence interval for the difference, –0.13 to –0.02 mmol/liter).

Conclusions: Short-term DHEA supplementation does not significantly affect measures of arterial stiffness or endothelial function in patients with adrenal insufficiency.