THE EFFECTS OF ESTROGEN ON ANXIETY-LIKE BEHAVIOR IN RODENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

The mechanisms by which estrogen hormone affects anxiety are unclear, but clinical observations related to increased anxiety related symptoms around menopausal age suggest that work in rodents may clarify important mechanistic details about this association. A key challenge in studying the effects of estrogen on defensive behavior in rodents is the plethora of inconsistent results. To address this issue, we conducted a systematic review and meta-analysis, examining the effects of estrogen injection on exploratory-defensive behavior in mice and rats using the elevated plus maze (EPM). This search yielded a total of 5 studies that satisfied our search criteria. Estrogen injection was not associated with changes in defensive behavior in rats (SE of the overall effect= 0.86, Variance V= 0.75, and effect size ES= 1.13). There was a considerable amount of publication bias between the studies. Importantly, in one study, where older rodents were used, the sensitivity of anxiety to estrogen injection was the highest. This suggested an age- dependent effect for estrogen on anxiety. Together, these findings suggest that the effects of estrogen on anxiety are more complicated that once thought. Although some studies show significant correlation between anxiety and estrogen, bias and inconsistent results suggest the conduction of more studies. Moreover, the age of the animal should be studied as an independent variable in future studies.