Effects of estrogen replacement on the progression of coronary-artery atherosclerosis

Background: Heart disease is a major cause of illness and death in women. T o understand better the role of estrogen in the treatment and prevention of heart disease, more information is needed about its effects on coronary at herosclerosis and the extent to which concomitant progestin therapy may mod ify these effects. Methods: We randomly assigned a total of 309 women with angiographically ve rified coronary disease to receive 0.625 mg of conjugated estrogen per day, 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate per day, or placebo. The women were followed for a mean (+/-SD) of 3.2+/-0 .6 years. Base-line and follow-up coronary angiograms were analyzed by quan titative methods. Results: Estrogen and estrogen plus medroxyprogesterone acetate produced si gnificant reductions in low-density lipoprotein cholesterol levels (9.4 per cent and 16.5 percent, respectively) and significant increases in high-dens ity lipoprotein cholesterol levels (18.8 percent and 14.2 percent, respecti vely); however, neither treatment altered the progression of coronary ather osclerosis. After adjustment for measurements at base line, the mean (+/-SE ) minimal coronary-artery diameters at follow-up were 1.87+/-0.02 mm, 1.84/-0.02 mm, and 1.87+/-0.02 mm in women assigned to estrogen, estrogen plus medroxyprogesterone acetate, and placebo, respectively. The differences bet ween the values for the two active-treatment groups and the value for the p lacebo group were not significant. Analyses of several secondary angiograph ic outcomes and subgroups of women produced similar results. The rates of c linical cardiovascular events were also similar among the treatment groups. Conclusions: Neither estrogen alone nor estrogen plus medroxyprogesterone a cetate affected the progression of coronary atherosclerosis in women with e stablished disease. These results suggest that such women should not use es trogen replacement with an expectation of cardiovascular benefit. (N Engl J Med 2000;343:522-9.) (C)2000, Massachusetts Medical Society.