Postmenopausal use of estrogen replacement therapy substantially reduces risk of coronary mortality at an age when untreated women show accelerated risk increases. This investigation is designed to evaluate the biobehavioral basis for this estrogen-related decrease in coronary risk, and to assess comparative benefits associated with estrogen use along, versus estrogen plus progesterone, versus placebo after 3 months and 6 months of treatment. This study will focus on possible changes in left ventricular structure and function which may result from reduced total peripheral resistance (TPR). The study sample will consist of 75 postmenopausal women aged 40-59. Fifty women will receive estrogen alone for 3 months, then half will continue with estrogen alone while the other half receives estrogen plus progesterone for the second 3 months. Finally, 25 women will receive only placebos for the full 6 months. Measures obtained at initial testing, retesting and final testing include: a) 24-hour ambulatory blood pressure; b) Doppler-validated, impedance-derived estimates of stroke volume, cardiac output and TPR as well as blood pressure at rest and after mental stressors; c) plasma beta-endorphin levels and responsivity to standardized pain tests, as well as pain threshold and tolerance measures; d) Doppler and echocardiographic measures of left ventricular mass index, relative wall thickness, contractility and arterial compliance. The following are the primary hypotheses to be tested: 1) Compared to placebo, treatment with estrogen alone is associated with lower 24-hour blood pressure, lowered TPR at rest and during stressors, included beta-endorphin responsivity, and better arterial compliance and left ventricular structure and function; 2) The addition of progesterone to estrogen results in less significant improvement in these measures compared to continuation of estrogen alone.
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