Women with the Metabolic Syndrome (central obesity, insulin resistance, and dyslipidemia) are at especially high risk for coronary heart disease (CHD). The prevalence of the Metabolic Syndrome increases with menopause and may partially explain the acceleration in CHD after menopause. Menopause is associated with increased central adiposity, insulin resistance, dyslipidemia (hypertriglyceridemia, increased low density lipoprotein (LDL), reduced high density lipoprotein (HDL) and small dense LDL particles), and increased thrombotic/inflammatory states, but there are no studies investigating the mechanisms that mediate these changes. The objectives of the proposed project are to investigate the emergence of the features of the Metabolic Syndrome in women followed prospectively through the menopause and determine if these features can be reversed with transdermal estrogen. We hypothesize that the increase in central adiposity with menopause will be a major contributor to the increased prevalence of the Metabolic Syndrome with menopause. This is the first prospective study to investigate the 1) effects of menopause and 2) estrogen replacement therapy (ERT) (oral vs. transdermal) on features of the Metabolic Syndrome. We will determine if the increase in central (intraabdominal)fat with menopause is associated with changes in lipids, insulin resistance, adipocytokines, and fibrinolytic/inflammatory markers. We will then determine if these changes can be reversed with transdermal ERT, as compared to oral ERT, which has pharmacologic effects on the liver.