Reproductive hormone sensitivity and risk for depression across the female life cycle: a continuum of vulnerability?

Throughout most of their lives, women are at greater risk for depression than men. Hormones and neurotransmitters share common pathways and receptor sites in areas of the brain linked to mood, particularly through the hypothalamic-pituitary-gonadal axis. It has been hypothesized that women presenting with episodes of depression associated with reproductive events (i.e., premenstrual, postpartum, menopausal transition) may be particularly prone to experiencing depression, in part because of a heightened sensitivity to intense hormonal fluctuations. The menopausal transition, for example, appears to represent a window during which some women might be more vulnerable to the development of first onset or recurrent depressive symptoms and major depressive episodes. In this review, we examine the association between hormone changes and increased risk of developing depression. Some of the underlying mechanisms that may contribute to such an increased risk are discussed critically, with a special emphasis on the events occurring during the menopausal transition. Last, we explore some of the clinical and therapeutic implications of hormone-modulated depression in women.