Endocrine Abstracts

DHEA and its sulfate ester DHEAS are the major steroids secreted by the adrenal zona reticularis. DHEA exerts its action either indirectly in peripheral target tissues following its conversion to potent sex steroids or directly as a neurosteroid. Moreover, there is growing evidence of high affinity binding sites on endothelial cells and lymphocytes suggestive of the presence of a specific DHEA receptor. Studies in patients with adrenal insufficiency (AI) have elucidated the role of DHEA. In women with AI circulating androgens are low and sexuality is impaired. Administration of oral DHEA not only increases circulating androgens in a dose-dependent manner but also improves libido, sexual satisfaction and well-being. The rapid downstream conversion of DHEA into androgens makes it a convenient tool for oral androgen replacement in women. In contrast to patients with AI, supplementation in patients with an age related decline in endogenous DHEA has been largely disappointing. However, there is limited evidence that in elderlies DHEA may positively affect bone mineral density, insulin sensitivity and may reduce abdominal fat. DHEA has significant pharmacological potential in women with anxiety, depression and autoimmune disease, as it has been shown to improve midlife dysthymia, negative symptoms in schizophrenia and disease activity in systemic lupus erythematosus (SLE).Major side effects are related to the androgenic activity of DHEA (acne, hirsutism). Diagnosis of DHEA availability still relies on measurements of DHEAS assuming that these steroids are freely interconvertible. However, recent evidence suggests that DHEAS cannot be converted back to the biologically active DHEA. Accordingly , there is growing evidence that DHEA/DHEAS ratios can be highly variable depending on DHEA sulfotransferase activity. These observations suggest the need of DHEA assays to evaluate the biological activity of the zona reticularis.