Dehydroepiandrosterone, a sex steroid metabolite in development for systemic lupus erythematosus

Abstract

Deficiency of the weak androgen dehydroepiandrosterone (DHEA) and its sulfoconjugated metabolite DHEA-S has been associated with a number of serious illnesses, including lupus, diabetes, Alzheimer’s disease and some cancers. Accordingly, supplementation with DHEA has been proposed for a variety of illnesses. Observational clinical studies and in vitro experiments have suggested that DHEA treatment might have a significant impact on immunological function, bone density, cognition, atherosclerotic disease, some malignancies, insulin resistance and obesity. Endogenous circulating DHEA levels, however, may vary widely by gender, age and ethnicity and can be affected by acute changes in corticosteroid production, alcohol intake, smoking, body mass index, medications and thyroid function [1-3]. Clearly, these variables complicate the interpretation of clinical data. DHEA also gives rise to a number of as yet poorly characterised metabolites, further confusing the assessment of its net effects when considered as treatment in heterogenous populations. Given the complexity of potential effects of DHEA and its metabolites, coupled to the diversity of clinical conditions that they might, at least in theory, affect, it is not surprising that clinical confirmation of efficacy in several clinical contexts has been inconsistent and controversial, hampering drug development in what might potentially be an important and widespread market. The current review will consider recent work suggesting efficacy of DHEA (GL-701, prasterone, Prestara™ [US], Anastar™ [Europe]; Genelabs) in systemic lupus erythematosus.