Effects of hormone replacement therapy on hemostatic cardiovascular risk factors

OBJECTIVES: From observational studies, there is evidence that hormone repl acement therapy in postmenopausal women causes a decrease in cardiovascular events. It remains unknown, however, precisely by which mechanisms this re duction is achieved. The primary aim of this work was to study the effects of hormone replacement therapy on established hemostatic risk factors durin g 1-year treatment of healthy postmenopausal women. The secondary aim was t o investigate whether there was any significant difference in these risk fa ctors between hormone replacement therapy administered as a cyclic estrogen /sequential progestogen or continuous estrogen/sequential progestogen regim en. STUDY DESIGN: Sixty postmenopausal women were randomized to treatment with estradiol valerate 2 mg/day either continuously or cyclic (days 1 to 21, pl acebo on days 21 to 28). Both groups received cyproterone acetate 1 mg/day on days 12 to 21. Blood samples were collected before treatment and on cycl e days 17 to 22 in cycles 3, 6, and 12. Thirty women with basic characteris tics identical to the women included in the treatment group were included a s a reference group. Blood samples were collected after 0, 6, and 12 months of observation. RESULTS: Hormone replacement therapy during 1 year caused a marginal but si gnificant increase in plasma concentration of factor Vile after 12 months o f treatment (P < .05), a significant decrease in fibrinogen, and a signific ant decrease in the protein concentrations of tissue-type plasminogen activ ator, plasminogen activator inhibitor-1, and lipoprotein(a) after 3, 6, and 12 months of treatment (P < .05). Possible differences in the integrated r esponse between the reference group and the hormone replacement therapy gro up were evaluated by comparison of the area under the curve as estimated in each individual on the basis of each analyte in the sampling periods. The area under the curve of fibrinogen was significantly lower in the hormone r eplacement therapy group than in the reference group (P < .03), whereas oth er variables did not deviate significantly between the groups. The areas un der the curve did not deviate significantly between the group that received cyclic estrogen/sequential progestogen and the group that received continu ous estrogen/sequential progestogen. CONCLUSIONS: One-year treatment with hormone replacement therapy influenced favorably a number of prognostic cardiovascular risk factors in healthy wo men. The most important effect was the lowering of fibrinogen. Furthermore, in this study the effect of hormone replacement therapy on hemostasis did not deviate between a cyclic estrogen/sequential progestogen regimen and a continuous estrogen/sequential progestogen regimen.