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The prophylactic effect of postmenopausal hormone replacement therapy on coronary atherosclerosis remains controversial. We, therefore, examined the influence of combined estrogen/progestin therapy on the progression of coronary calcium as a marker of coronary atherosclerosis. We determined the extent of coronary calcium in 277 women (age 57 +/- 6 years, time after menopause 3.9 +/- 2.4 years, group I) at the beginning of hormone replacement therapy using multislice computed tomography. For quantification, we calculated the volume score. After an observation period of 3 years, we determined the progression of coronary calcium in a second scan. The results were compared with those from an age- and risk factor-adjusted group of postmenopausal women without hormone substitution (group II). No significant difference was found in the volume score (59 +/- 95 vs 58 +/- 88) or risk factor distribution between the 2 groups on study entry. In 56 women of group I and 52 women of group II, coronary calcium could be excluded on the initial scan (p = NS). After a mean observation time of 38.5 +/- 4.9 months, we observed no significant difference between the 2 groups regarding an increase in volume score (17 +/- 24 vs 19 +/- 27, p = NS) or the fraction of women with an increase in volume score (82.2% vs 84.2%). In conclusion, a reduced progression of coronary calcium in postmenopausal women on combined estrogen/progestin therapy could not be observed compared with a matched group of women without hormone substitution.