This generally well-conducted review found that DHEA treatment may to a small extent improve health-related quality of life and symptoms of depression in women with adrenal insufficiency. There was insufficient evidence to support its routine use. The authors' conclusions are likely to be reliable.

To assess the effect of dehydroepiandrosterone (DHEA) treatment on health-related quality of life (HRQOL) in women with adrenal insufficiency.

MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, CINAHL and PsycINFO were searched from inception to July 2008. Search terms were available upon request. No language restrictions were applied to the search.

Randomised trials of women with primary or secondary adrenal insufficiency who were treated with at least 20mg DHEA per day for at least two weeks were eligible for inclusion. Included studies measured at least one psychosocial element of HRQOL such as physical and mental health, social functioning and sexuality.

Trials enrolled middle-aged women with primary and/or secondary adrenal insufficiency; one trial enrolled young women with panhypopituitarism. Most studies administered DHEA as 50mg daily for a duration of between three and 12 months. Several questionnaires were used to measure HRQOL, such as 36-item Short Form Health Survey (SF-36), Beck Depression Inventory and other general HRQOL surveys.

Two reviewers independently performed study selection. Any differences were resolved by consensus or arbitration.

Two reviewers independently assessed methodological quality of the studies by evaluating use of allocation concealment, blinding and losses to follow-up. Disagreements were resolved by consensus or arbitration.

Data were extracted for calculation of standardised mean differences (SMD) and corresponding 95% confidence intervals (CI) between DHEA and placebo treatment arms. Authors were contacted for additional data where needed.

Two reviewers independently extracted data. Disagreements were resolved by consensus or arbitration

Pooled mean differences and 95% CIs were calculated using a random-effects model. Statistical heterogeneity was evaluated using the I² test. Subgroup analyses were performed to evaluate the effect on results of adrenal insufficiency type, dose and duration of intervention, study design and study quality

Ten trials (n=264) were included in the review. Allocation concealment was reported in five trials. Blinding of patients was reported in all 10 trials. Two trials reported losses to follow-up of more than 20%. Unpublished data was included from one of the trials.

Pooled global HRQOL scores showed a small statistically significant benefit of DHEA treatment compared to placebo (SMD 0.21, 95% CI 0.08 to 0.33, I² =32%; nine trials). Significant benefits of similar magnitude were also found for depression (SMD 0.23, 95% CI 0.04 to 0.42, I² = 57%; seven trials). There were no statistically significant benefits found for anxiety (five studies) or sexual well being (four studies).

Five studies were included in an analysis of pooled data from each domain of the the SF-36. There was a statistically significant benefit of DHEA treatment compared to placebo for the physical subscale (SMD 4.2, 95% CI 0.04 to 8.3, I²=52%). No differences were reported between DHEA treatment and any other SF-36 subscale.

No serious adverse events were reported in any of the trials. Androgenic side effects reported included greasy skin, hirsutism, acne, scalp itching and increases in apocrine sweat and odour and were generally well tolerated.

There were no differences between groups reported for any of the subgroup analyses that evaluated effects of adrenal insufficiency type, dose and duration of intervention, study design and study quality.

Treatment with DHEA may improve health-related quality of life and depression to a small extent in women with adrenal insufficiency. There was no effect on anxiety and sexual well being. There was insufficient evidence to support routine use of DHEA treatment in such patients.

The review addressed a clear question and criteria for inclusion were clearly stipulated. No language restrictions were applied to the search. There was no specific search for unpublished literature, so there was a risk of publication bias. Steps were taken to minimise errors and bias during all parts of the review process and the authors attempted to attain missing data from the authors of the included trials. Study details were provided. The appropriateness of pooling results derived from different questionnaires of quality of life was unclear and there was moderate heterogeneity reported for all the analyses that found significant benefits of DHEA treatment. The review was generally well conducted. The authors' cautious conclusions regarding the results were justified and are likely to be reliable.

Practice: The authors did not state any implications for practice.

Research: Therapeutic trials of DHEA treatment may be justified in patients with significant reductions in health-related quality of life; these should ideally take place within an n-of-1 trial (single participant) that involved pairs of alternating treatments replicated until differences in treatments were clear to clinician and patient.

Not stated.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.