In a six-week, double-blind study, DHEA was both an adjunct to treatment and a monotherapy (Wolkowitz et al., 1999). Participants were 22 individuals with major depression (20 with unipolar depression and two with bipolar II disorder, depressed phase) meeting DSM-IV criteria and pre-study ratings of greater than or equal to 16 on the HAM-D. Participants were also medication-free or had been stabilized on an antidepressant medication for greater than or equal to 2 months. Five of the 11 patients treated with DHEA showed a 50% or greater decrease in depressive symptoms; however, this was not seen in the 11 patients given placebo. No differential effect of sex or pre-existing medication status (medication-free versus stabilized antidepressant regimen) was found through subgroup analyses.
Wolkowitz et al. (1999) explained that the mechanisms by which DHEA might have mood-elevating or antidepressant effects were unclear but suggested some possibilities. Dehydroepiandrosterone is partially metabolized to testosterone and estrogen, both of which may have mood effects of their own. Also, DHEA may modulate the bioavailability of testosterone by means of allosteric changes in albumin's affinity for testosterone. In discussing other possible mechanisms of action, Legrain and Girard (2003) noted, "[DHEA-S] is a neurosteroid which modulates neuronal excitability via specific interactions with neurotransmitter receptors and DHEA is an activator of calcium-gated potassium channels."
Beyond treating depression, Binello and Gordon (2003) have noted that evidence is accruing in support of DHEA supplementation for schizophrenia, adrenal insufficiency, hypopituitarism, osteoporosis and systemic lupus erythematosus.
Strous and colleagues (2003), in a double-blind trial, investigated the efficacy of DHEA in the management of negative symptoms of schizophrenia. Significant improvement was found in individuals receiving DHEA in negative symptoms (p<0.001) as well as in depressive (p<0.05) and anxiety (p<0.001) symptoms.
Baulieu and colleagues (2000) conducted a double-blind, placebo-controlled, one-year trial of oral DHEA 50 mg/day with 280 men and women ages 60 to 79 (the so-called "DHEAge Study") and found some effects on bone turnover, skin and libido. In addition to the re-establishment of a "young" concentration of DHEA-S, small increases in testosterone and estradiol(Drug information on estradiol) were noted, particularly in women. In women who were older than 70, bone turnover improved selectively as assessed by the dual-energy X-ray absorptiometry (DEXA) technique, and there was a decrease of osteoclastic activity. Also in these older women, a significant increase in most libido parameters was found. In terms of hydration, epidermal thickness, sebum production and pigmentation, improvement of skin status was observed, again particularly in women. The investigators concluded that a number of biological indices confirmed "the lack of harmful consequences of this 50 mg/day DHEA administration over one year, also indicating that this kind of replacement therapy normalized some effects of aging, but does not create 'supermen/women' (doping)."
Genelabs Technologies, Inc., has funded several studies of a synthetic form of DHEA (Prestara) for the potential treatment of systemic lupus erythematosus. In August of 2002, the U.S Food and Drug Administration issued an approvable letter for the Prestara New Drug Application. Additionally, the National Institutes of Health is studying DHEA as an alternative HIV/AIDS therapy (Heavey, 2004).
Side effects of DHEA therapy in women have included increased facial hair, weight gain, acne, temporary breast tenderness, loss of head hair and skin rash (Munarriz et al., 2002). Doses above 1500 mg/day have been known to result in insulin resistance in humans and pre-neoplastic pancreatic lesions in rats (Alternative Medicine Review, 2001). Potential interactions between DHEA and pharmaceuticals include enhanced sedation seen in patients on benzodiazepines and related central nervous system active drugs.