The adrenal hormone dehydroepiandrosterone (DHEA) and its sulphated ester (DHEAS) are together the most abundant of steroid hormones in both sexes. Blood levels are high in young adults and decrease with advancing age. There is some epidemiological evidence that relatively high serum DHEAS levels in males may protect against heart disease and be associated with increased longevity. In the USA there is growing public enthusiasm for DHEA supplementation as a means of retarding ageing and age-associated cognitive impairment but there is very little evidence from controlled trials. In two trials DHEA was associated with a deleterious effect on visual memory after a psychosocial stressor and quality of life measures, but there is inconsistent systematic evidence of adverse effects from DHEA. Longer-term randomized placebo controlled trials are needed for low and high doses.
What little evidence there is from controlled trials does not support a beneficial effect of DHEA supplementation on cognitive function of non-demented middle-aged or elderly people. There is inconsistent evidence from the controlled trials about adverse effects of DHEA.
In view of growing public enthusiasm for DHEA supplementation, particularly in the USA, and the theoretical possibility of long-term neuroprotective effects of DHEA there is a need for further high quality trials in which the duration of DHEA treatment is longer than one year, and the number of participants is large enough to provide adequate statistical power. Cognitive outcomes should be assessed in all trials.
In view of the theoretical possibility of beneficial effects of DHEA retarding age-associated deterioration in cognitive function, we have reviewed studies in this area.
To establish whether administration of DHEA improves cognitive function or quality of life or reduces the rate of decline of cognitive function in normal older adults.
The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS were searched on 18 March 2008 using the terms: dhea*, prasterone, dehydroepiandrosterone*. The CDCIG Specialized Register contains records from all major health care databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many clinical trials registries and grey literature sources.
Relevant journals, personal communications and conference abstracts were searched for randomized controlled trials investigating the effects of DHEA/S on cognition in older adults.
All randomized placebo-controlled trials enrolling people aged over 50 without dementia and to whom DHEA in any dosage was administered for more than one day were considered for inclusion in the review.
Data for the specified outcomes were independently extracted by two reviewers (JGE and RM) and cross-checked. Any discrepancies were discussed and resolved. No data pooling was undertaken owing to the lack of availability of the relevant statistics.
Five studies provided results from adequate parallel-group data. Barnhart 1999 and Dayal 2006 enrolled perimenopausal women with complaints of decreased well being and, using three cognitive measures, found no significant effect of DHEA compared with placebo at 3 months. Wolf 1998b enrolled 75 healthy volunteers (37 women and 38 men aged 59-81) in a study of the effect of DHEA supplements on cognitive impairment induced by stress; after two weeks of treatment, placebo group performance deteriorated significantly on a test of selective attention following a psychosocial stressor (p<0.05), while deterioration was not evident in the DHEA group (p=0.85). However, when compared with placebo, DHEA was associated with significant impairment on a visual memory recall test (p<0.01) following the stressor. No significant effects were found on a third cognitive task. Effects were not found on tasks when administered in the absence of a stressor. van Niekerk 2001 found no effect on cognitive function in 46 men aged 62-76 from three months of DHEA supplementation. Nair 2006, enrolled 57 women and 87 men with low level of sulphated DHEA in a 24-month study, no significant changes in quality of life measures for either sex were found. In Von Muhlen 2008 DHEA for one year showed no benefit on cognition performance in 225 healthy older people. Reduced performance in a visual memory recall test observed in one trial and a significant drop-out rate in favour of placebo emerged in another trial.