The role of neurosteriod fluctuation in perimenopausal depression

Abstract

There is a well-established increase in depression risk during the menopause transition – known as perimenopausal depression. Increased fluctuation of estradiol has long been thought to be an important causal factor in perimenopausal depression, and recent research suggests that increases, decreases, or absolute changes in estradiol may be associated with depressive symptoms in different subsets of perimenopausal women. However, the mechanisms by which estradiol differentially influences mood are still very unclear. Preliminary evidence suggests that estradiol may increase vulnerability to developing depressive symptoms through the effects of a neurosteroid called allopregnanolone. In the current study, the role of estradiol and allopregnanolone was examined in 26 perimenopausal participants experiencing disturbed mood. Fifteen weekly measurements of depressive symptoms as well as plasma levels of estradiol, progesterone, and allopregnanolone were collected. In 10 participants with a sufficient number of weeks of hormone data available, correlational analysis revealed that every participant displayed a significant relationship between depressive symptoms and changes in at least one neurosteroid. Although mood sensitivity to progesterone was correlated with mood sensitivity to allopregnanolone, estradiol and allopregnanolone sensitivity indicators appeared not to be related. Our results suggest that fluctuations in neurosteroids in the menopause transition play an important role in perimenopausal depressed mood. Future research is needed to clarify whether estradiol and allopregnanolone changes each play an independent role in exerting effects on perimenopausal mood or work in tandem.