The menopause transition is associated with a pronounced increase in risk of cardiovascular disease. Hormone replacement therapy in postmenopausal women reduces the risk of cardiovascular disease by approximately 50%, although the mechanisms involved are poorly understood. We will examine the impact of hormone replacement therapy on metabolic risk factors affecting cardiovascular disease and future health in aging women. Our overall hypothesis is that hormone replacement therapy in the early postmenopausal period reduces the central accumulation of body fat and improves insulin sensitivity, thus reducing metabolic risk factors for cardiovascular disease. A total of 72 women will be recruited for this 2-year randomized double- blinded placebo- controlled longitudinal study. We will measure outcomes of changes in body fat distribution and insulin sensitivity on 4 occasions (baseline, 6 months, 1 year and 2 years) in women taking continuous conjugated estrogens plus medroxyprogesterone acetate or placebo. Our study will assess the temporal sequence of changes in outcome variables to provide insight into whether changes in body fat distribution precede alterations in insulin sensitivity. We will use: 1) computerized tomography (CT) and dual photon x-ray absorptiometry (DEXA) scanning to measure intra-abdominal body fat and total body fat, and 2) euglycemic clamps to measure insulin sensitivity. Analysis of these data will provide an understanding of the impact of hormone replacement on the syndrome of central obesity and insulin resistance, which predisposes women to cardiovascular disease. In addition, our study may allow physicians to target hormone replacement to women with specific body compositions.
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