It is increasingly axiomatic that depression has widespread adverse physiological effects, and conversely that a variety of physiological systems impact the risk for developing depression. This convergence of depression and altered physiology is particularly dramatic during midlife-a time during which reproductive failure presages dramatic increases in prevalence of both heart disease and depression. The potentially meaningful and illuminating links between estrogen (E2) deficiency, cardiovascular disease (CVD), and depression have largely been obscured, first by assertions, subsequently repudiated that the perimenopause was not a time of increased risk of depression, and more recently by the denegration of hormone replacement therapy by initial reports of the Women's Health Initiative. Increasingly, however, research has led to unavoidable conclusions that CVD and depression share common and mediating pathogenic processes and that these same processes are dramatically altered by the presence or absence of E2. This review summarizes data supporting this contention with the intent of placing depression and E2 therapy in their proper physiologic context.
© 2011 Wiley-Liss, Inc.