Estradiol administration differentially affects the response to experimental psychosocial stress in post-menopausal women with or without a history of major depression

J Affect Disord. 2020 Jan 15;261:204-210. doi: 10.1016/j.jad.2019.09.074. Epub 2019 Sep 30.


Background:: The effects of estradiol on the brain regions involved in the response to stress and emotional processes may be particularly important in women who have alterations in these systems that make them vulnerable to Major Depressive Disorder (MDD). This study examined whether the effect of estradiol administration on the subjective distress and mood response to a laboratory-based psychosocial stress task differs in women with and without a history of MDD.

Methods:: Participants were 65 euthymic postmenopausal women, with and without a history of MDD. They received either 3 months of open-label oral estradiol or did not receive estradiol. After 3 months, participants completed the Montreal Stress Imaging Task (MIST) and subjective distress and mood ratings.

Results:: The effect of estradiol on subjective distress following the MIST differed based on MDD history. In women without a history of MDD, estradiol administration was associated with greater subjective distress than no estradiol. However, in women with a history of MDD, estradiol administration was associated with less subjective distress compared to no estradiol.

Limitations:: This study included open-label administration of estradiol and participants were not blinded to administration. Interpretation of result should include consideration of the relatively small group sizes and that results may not generalize to currently depressed individuals.

Conclusions:: In euthymic women with a history of MDD, estradiol may benefit the affective response to psychosocial stress while having comparatively little benefit in women with no MDD history. Further work should explore whether estradiol administration reduces the risk of depression recurrence in post-menopausal women with past MDD.