Perimenopausal Estrogen Replacement Therapy Study

Study Background and Objectives: In the U.S. the majority of heart disease deaths are in
women, not men. Much of the gender disparity in CVD rates relate to the burden of CV risk in
women after the menopause. Depression has been associated with an increased risk for CVD
morbidity and mortality. Even histories of recurrent depression in euthymic individuals are
associated with elevated CV risk. Understanding the depression-CVD link may have particular
relevance for women since women experience depression at a rate twice that of men.
Substantial convergent evidence indicates that ovarian failure (estrogen deprivation) is one
likely mechanism contributing to both CVD and depression in women. The perimenopause, a time
associated with a two-fold increase in rates of depression, may provide an ideal opportunity
for studying the pathophysiology of CV risk and depression in women.

The primary objective of this study is to examine the prophylactic role of estradiol in the
development of depressive symptoms and the progression of cardiovascular risk in
perimenopausal women with or without histories of depression. The investigators predict that
women susceptible to depression will be particularly vulnerable to the acceleration of CVD
in the context of the perimenopause and, consequently, will show differentially greater
benefit of estradiol treatment during the menopause transition for both indices of CV risk
(e.g. inflammation, endothelial function, stress reactivity), as well as depressive
symptoms.