Although epidemiological data indicate that the postmenopausal use of estrogen is associated with significant reductions in risk for coronary mortality, analyses of these data separately by smoking status reveal that the protective effects of hormone replacement therapy (HRT) may be eliminated in women smokers. Alterations in the hepatic metabolism of estrogen have been demonstrated in female smokers and this may be the mechanism rendering oral estrogen ineffective is postmenopausal smokers. Thus, the primary purpose of this study is to examine the differential effectiveness of transdermally administered estrogen (plus progesterone) versus orally administered estrogen (plus progesterone) in 108 postmenopausal women smokers. A secondary goal of this study is to insure the inclusion of an undeserved population of women, thus one half of the investigators~ sample will represent postmenopausal women smokers residing in rural North Carolina, yielding a more diverse study population in areas of socioeconomics as well as cultural and social factors. Using a randomized, placebo controlled trial, each will be initially tested for cardiovascular stress reactivity, including cardiac output and total peripheral resistance, for beta-adrenergic receptor responsivity and for measures of blood flow and vascular hypertrophy and resistance. Then, women will be randomly assigned to either 4 months of transdermal estrogen plus progesterone (n=36), or 4 months of transdermal or oral placebo (n=36). Each will be retested at the end of this intervention period. Since transdermal estrogen delivery avoids the hepatic """"""""first-pass"""""""" effect, the investigators hypothesize that transdermal estrogen will be significantly more effective for smokers in reducing vascular tone, increasing beta-adrenergic receptor responsivity and reducing blood pressure than oral administration. Thus, this study is expected to have clinical implications for effective hormone treatment in women smokers.
