Dehydroepiandrosterone and Its Metabolite 5-Androstenediol: New Therapeutic Targets and Possibilities for Clinical Application

Abstract

Dehydroepiandrosterone and its sulfate are the most abundant steroids in humans. The metabolism of dehydroepiandrosterone can differ significantly depending on the organ or tissue and the subtype of steroid receptors expressed in it. For dehydroepiandrosterone, as a precursor of all steroid hormones, intracrine hormonal activity is inherent. This unique feature could be beneficial for the medicinal application, especially for the local treatment of various pathologies. At present, the clinical use of dehydroepiandrosterone is limited by its Intrarosa® (Quebec city, QC, Canada) prasterone) 6.5 mg vaginal suppositories for the treatment of vaginal atrophy and dyspareunia, while the dehydroepiandrosterone synthetic derivatives Triplex, BNN 27, and Fluasterone have the investigational status for the treatment of various diseases. Here, we discuss the molecular targets of dehydroepiandrosterone, which open future prospects to expand its indications for use. Dehydroepiandrosterone, as an oral drug, is surmised to have promise in the treatment of osteoporosis, cachexia, and sarcopenia, as does 10% unguent for skin and muscle regeneration. Also, 5-androstenediol, a metabolite of dehydroepiandrosterone, is a promising candidate for the treatment of acute radiation syndrome and as an immunostimulating agent during radiopharmaceutical therapy. The design and synthesis of new 5-androstenediol derivatives with increased bioavailability may lead to the appearance of highly effective cytoprotectors on the pharmaceutical market. The argumentations for new clinical applications of these steroids and novel insights into their mechanisms of action are discussed.