Effect of dehydroepiandrosterone therapy on cognitive performance among postmenopausal women: a systematic review of randomized clinical trial data

This systematic review of randomized controlled trials evaluated the existing evidence on the effect of exogenous dehydroepiandrosterone (DHEA) on cognitive performance in postmenopausal women. The overall fi ndings do not support a therapeutic benefi t of DHEA on cognitive performance, although a statistically signifi cant improvement was seen in fi ve out of six tests of visual-spatial performance in one small study. ImportanceWhether dehydroepiandrosterone (DHEA) supplementation improves cognitive performance in older women is uncertain. Nonetheless, DHEA supplements are readily available over the counter in several countries and are potentially being used to prevent cognitive decline and dementia.ObjectiveThis systematic review was conducted to evaluate the effect of exogenous DHEA on cognitive performance in postmenopausal women.Evidence ReviewOvid MEDLINE, EMBASE, PsycINFO, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials databases were searched for studies of postmenopausal women until November 30, 2022. Eligible studies were required to be randomized clinical trials, be at least single blind, have a placebo or comparator arm and published in English. Risk of bias of the included studies was assessed by the revised Cochrane risk-of-bias tool.FindingsOf the 15 articles retrieved for full-text review, four met the inclusion criteria. In all studies DHEA was administered as a 50-mg oral daily dose and all were double blind with an identical placebo. Three were placebo-controlled, crossover studies and one was a parallel-group clinical trial. The only positive outcome was limited to a 4-wk cross-over study in which DHEA statistically significantly enhanced five of six tests of visual-spatial performance compared with placebo in 24 cognitively normal postmenopausal women. Improvement in cognitive performance with DHEA treatment over placebo group was not seen in any other study. Heterogeneity of design and use of multiple measures of cognitive performance was a barrier to meta-analysis and between study comparisons. The studies were limited by high risk of bias in multiple domains.Conclusion and RelevanceOverall, this systematic review does not support a beneficial effect of DHEA therapy on cognitive performance in postmenopausal women.