The Use of Dehydroepiandrosterone Therapy in Clinical Practice

Abstract

Dehydroepiandrosterone (DHEA) therapy is controversial due to sensationalized reports of epidemiologic studies and the over-the-counter availability of DHEA. Human clinical trials have investigated the potential efficacy of DHEA therapy in multiple conditions with resultant inconsistencies in findings. DHEA is unique compared with other adrenal steroids because of the fluctuation in serum levels found from birth into advancing age. The lower endogenous levels of DHEA and DHEA sulfate found in advancing age have been correlated with a myriad of health conditions. Also, some studies suggest gender-specific actions of endogenous and exogenous DHEA. We reviewed only pharmacokinetic studies and human clinical trials investigating the efficacy of DHEA therapy that were placebo-controlled as these provided the most reliable scientific basis for the evaluation of DHEA therapy. Pharmacodynamic studies suggest that doses of 30-50mg of oral DHEA may produce physiologic androgen levels, especially in women. These studies report a dose-dependent effect and lack of accumulation of serum androgen levels. Pharmacologic studies also reveal a gender-specific response to DHEA therapy such that testosterone levels are increased in women but not in men. Clinical trials suggest that 50mg of oral DHEA, but not <30mg, can increase serum androgen levels to within the physiologic range for young adults with primary and secondary adrenal insufficiency, possibly improve sexual function, improve mood and self-esteem, and decrease fatigue/exhaustion. Whereas DHEA replacement therapy may be effective in treating patients with adrenal insufficiency, human clinical trials investigating its efficacy in conditions such as systemic lupus erythematosus, HIV, Alzheimer disease, advancing age, male sexual dysfunction, perimenopausal symptoms, depression, and cardiovascular disease have not provided consistent findings.

Androgen in postmenopausal women

“…Wolkowitz et al only reported that DHEA treatment had significant beneficial effects on depressive symptoms in patients with major depression (77). Cameron et al suggested that doses of 30 to 50 mg of oral DHEA produce physiological androgen levels and that 50 mg of DHEA increases serum androgen levels within the physiological range as well as possible improvements of sexual function and mood and decrease in fatigue/exhaustion in women (78). A recent study has revealed that intravaginal administration of DHEA can be used to treat vaginal atrophy (79).…”

Differential scanning calorimetry as a screening technique in compatibility studies of DHEA extended release formulations

“…lipid metabolism, atherosclerosis, osteoporosis [16][17][18][19][20]. Moreover, it has been demonstrated that DHEA treatment can improve mood, well-being, sexual functions and cognition in young adults with primary and secondary adrenal insufficiency [21,22]. Pharmacodynamic studies suggest that daily doses of 30-50 mg of oral DHEA may produce physiologic hormone levels [22].…”

Sex-based differences in regulatory T cells.

“…More detailed studies have been performed in recent years to evaluate the potential role of androgen in the prevention/cure of autoimmune diseases like SLE, with results that generally suggest that androgens are responsible for the protection against autoimmune disease. In some of such studies the role of testosterone in the treatment of SLE was emphasized, wherein the administration of various forms of the steroid alleviated SLE, or SLE development was seen to occur if levels of testosterone dropped (87,117,(153)(154)(155). In the Lupus prone NZB x NZW mice, more suppressor cells were generated in the presence of testosterone, suggesting their role in protecting susceptible mouse strains from the production of autoantibodies (156).…”

“…In some of such studies the role of testosterone in the treatment of SLE was emphasized, wherein the administration of various forms of the steroid alleviated or modified the course of SLE in both females and males (87,117,(153)(154)(155)188). a).…”

“…Others have shown that TGF-β is a cytokine, mediating generalized control of autoimmunity (65,(71)(72)(73)(74)(75) and oral tolerance (76 (87)(88)(89). CD103 is also expressed by lymphocytes within the bronchial epithelium, by some alveolar wall lymphocytes, and by bronchoalveolar fluid T cells (90,91).…”