The role for long-term use of dehydroepiandrosterone in adrenal insufficiency

Dehydroepiandrosterone (DHEA) is an androgen produced by the zona reticularis of the adrenal gland. Patients with adrenal insufficiency will have a deficiency of DHEA. Unlike glucocorticoid and mineralocorticoid replacement, DHEA supplementation is not considered essential for life and is therefore not routinely replaced in adrenal failure. DHEA deficiency is associated with morbidity, including adverse impacts on metabolic function, quality of life and sexuality in multiple studies. The role for replacement, however, remains unclear.

The benefits of DHEA supplementation have been definitively demonstrated in a number of historical studies of patients with primary and secondary adrenal insufficiency. Beneficial impacts on quality of life, body composition, bone health and metabolic markers have been demonstrated. However, published data are inconsistent; controversies persist around the exact role of DHEA replacement and around which patient cohorts are most likely to benefit. There is also a paucity of recent randomized controlled trials in the medical literature to inform on optimal dose and duration of DHEA replacement in adrenal failure.

Here, we review the evidence for DHEA supplementation in patients with adrenal insufficiency. We highlight knowledge gaps in the medical literature and areas that should be prioritized for future research endeavours.