DHEA: Dehydroepiandrosterone

Disclosures

Am J Health Syst Pharm. 2000;57(22) 

In This Article

Clinical Studies

To date, clinical studies of DHEA in patients with specific diseases have yielded generally inconclusive results. Most of the studies were open label or had very small samples. Most of the studies discussed below were randomized, double-blind, placebo-controlled trials in which the oral dosage was gt_300 mg/day. Tummala and Svec [37] demonstrated that incremental increases in serum DHEA and DHEAS levels appear to plateau at an oral DHEA dosage of 300 mg/day and inferred that doses greater than this have little additional therapeutic value.

Postmenopausal Bone Density

In a randomized, double-blind, placebo-controlled study by Baulieu et al.,[10] 280 healthy men and women ages 60-79 years were given DHEA 50 mg/day orally for 12 months. Increases in bone mineral density (p < 0.05) and decreases in biochemical markers of bone turnover (p < 0.01 for serum C-terminal peptide and p < 0.05 for serum bone alkaline phosphatase) were observed at 12 months in women older than 70 but not in any other subgroup.

Systemic Lupus Erythematosus

DHEA supplementation has shown promise for the treatment of SLE. In a randomized, double-blind trial,[38,39 28] women with SLE received DHEA 200 mg/day for three months. In the DHEA group, the SLE Disease Activity Index score and both the patients' and the physicians' overall assessments of disease activity decreased, whereas small increases were seen in the placebo group. However, significance was achieved only for the visual-analogue- scale component of the index (p = 0.022). Lupus flares occurred less frequently in the treatment group than in the placebo group (three versus eight flares, p = 0.053), and a nonsignificant decrease in prednisone requirements was noted in the treatment group (from a mean ± S.D. daily dose of 12.4 ± 3.2 mg to 9.1 ± 2.3 mg, compared with an increase from 5.3 ± 1.37 mg to 7.3 ± 2.9 mg in the placebo group). Serum titers of antibodies to double-stranded DNA and levels of complement components C3 and C4 did not change significantly between the groups.

Well-being and Cognition

In a randomized, placebo-controlled, crossover trial, 30 patients ages 40-70 years were given 50 mg of DHEA orally daily.9 Within two weeks, this dose restored serum DHEA levels in both men and women to those found in young adults. With DHEA treatment, 67% of the men and 84% of the women perceived an increase in physical and psychological well-being. However, the study has been criticized for its use of an open-ended questionnaire for self-assessment of well-being.[40]

At present, there are no rigorous data to support an improvement in memory or other aspects of cognitive function after DHEA replacement therapy. Low endogenous levels of DHEA and DHEAS do not appear to be associated with an increased risk of dementia.[41]

Depression

The possible relationship between depression and serum DHEA and DHEAS levels is intriguing; however, more research is needed. Some authors have suggested that abnormal diurnal variations in serum DHEA and DHEAS levels, as well as abnormally high cortisol- to-DHEA ratios, may be causative factors in depression in adults and depression with comorbid panic or phobic disorders in adolescents.[3,42,43,44]

In a randomized, double-blind trial by Wolkowitz et al.,[45] 22 patients who had major depression (a Hamilton Rating Scale for Depression [HAM-D] score of 16 or greater) and who were either medication free or stabilized on antidepressant regimens received DHEA (30 mg/day for weeks 1 and 2, 60 mg/day for weeks 3 and 4, and 90 mg/day for weeks 5 and 6) or placebo. At the end of the six weeks, the mean decrease in the HAM-D score was 30.5% in the treatment group and 5.3% in the placebo group (p < 0.04). Five of 11 patients in the treatment group were considered responders (at least a 50% decrease in HAM-D score), compared with none of the 11 patients in the placebo group.

Effects in HIV-Infected Patients

In a recent open-label trial evaluating the effect of DHEA on depressed mood and fatigue, 45 HIV-positive patients (39 men and 6 women) received oral DHEA doses of 200-500 mg/day for eight weeks.[11] Of the 32 patients who completed the trial, 23 (72%) had an improvement in mood and 26 (81%) had a reduction in fatigue. There was a significant increase in body cell mass and libido but no effect on CD4+ lymphocyte counts or testosterone levels in men. The positive effects on mood, fatigue, and body cell mass continued for an additional four weeks in a subsequent double-blind phase of the study. Christeff et al.[46] have noted an inverse relationship between serum DHEA and DHEAS levels and the immunologic deterioration in HIV patients, which suggests a role for DHEA and other androgens in the normal functioning of the immune system.

Effects on Physical Variables

A randomized, double-blind, placebo-controlled crossover trial by Morales et al.[21] looked at the effects of oral DHEA 100 mg/day in 16 subjects 50-65 years of age. Baseline levels of serum DHEA, DHEAS, androstenedione, testosterone, and dihydrotestosterone were at or below the low end of the range for young adults. In both sexes, DHEA 100 mg/day restored serum DHEAS to levels at or slightly above the upper limit of the young-adult range. In women, androstenedione, testosterone, and dihydrotestosterone were increased to three to five times baseline levels (p < 0.001 for each hormone), or to levels above the sex-specific ranges for young adults, whereas in men only androstenedione was significantly increased above baseline (p < 0.05). Serum IGF-1 levels increased by a mean ± S.D. of 16% ± 6% (p = 0.04) in men and 31% ± 12% in women (p = 0.02). In men but not women, fat body mass decreased by 6.1% ± 2.6% (p = 0.02), and there were increases in knee muscle strength (15.0% ± 3.3%, p = 0.02) and lumbar back strength (13.9% ± 5.4%, p = 0.01). No changes in basal metabolic rate, bone mineral density, urinary pyridinoline cross-links, fasting insulin, glucose, cortisol, or lipids were observed in either sex.

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