Dehydroepiandrosterone substitution in female adrenal failure: no impact on endothelial function and cardiovascular parameters despite normalization of androgen status.

Summary Background  Female adrenal insufficiency implicates reduced production of the adrenal androgen precursor dehydroepiandrosterone (DHEA) and low androgen levels. Oral DHEA restores androgen deficit but the clinical implications and safety of substitution therapy is uncertain. A putative DHEA receptor in vascular endothelium has been described and in vitro studies have shown involvement of DHEA in NO dependent pathways. Aim  To evaluate effects of DHEA substitution on cardiovascular parameters. Design  Six months randomized, double-blind, placebo-controlled crossover study. Treatment consisted of DHEA 50-mg or placebo. Each treatment period was followed by a 2-month washout period. Material and methods  Ten females with documented adrenal failure were included. Androgen levels were measured. Cardiovascular evaluation was performed before and after every treatment period. Two patients left the study because of skin side effects and anxiety, respectively. All patients had low circulating androgens baseline and normal range androgens during DHEA treatment. We examined patients with noninvasive endothelial cell function, magnetic resonance imaging (MRI)-based cardiac output, echocardiography, ambulatory 24-h blood pressure and maximal oxygen consumption. Results  DHEA treatment normalized androgen status to levels seen in healthy women. DHEA and placebo treatment had no effect on echocardiographic parameters of myocardial dimensions or systolic and diastolic function, noninvasive endothelial cell function at the level of the brachial artery, 24-h blood pressure and heart rate, cardiac output and maximal oxygen consumption during exercise cycle testing. Remarkably, all participants had evidence of concentric left ventricular remodelling by echocardiography. Conclusion  Restoration of physiological androgen levels using 6 months of DHEA replacement in this pilot study did not affect cardiovascular parameters and endothelial function in female adrenal insufficiency.