Effects of continuous estrogen and estrogen-progestin replacement regimenson cardiovascular risk markers in postmenopausal women

Objective: To evaluate the influence of 2 continuous combined estrogen-prog estin replacement products, compared with unopposed estrogen and placebo, o n cardiovascular risk markers in postmenopausal women in a randomized, doub le-blind, placebo-controlled trial. Methods: Two hundred seventy healthy postmenopausal women were randomly ass igned to 1 of 4 treatment groups: placebo, unopposed 17-beta estradiol(1 mg ), 1 mg of 17-beta estradiol with 0.25 mg of norethindrone acetate, or 1 mg of 17-beta estradiol with 0.5 mg of norethindrone acetate. The primary out come variable was change from baseline in low-density lipoprotein cholester ol concentration. Additional outcome variables included changes in other se rum lipid levels, hemostatic variables, and indicators of carbohydrate meta bolism. Results: The low-density lipoprotein cholesterol level was reduced to a sim ilar degree in all groups receiving active treatment (10%-14% from baseline ; P=.001 for 17-beta estradiol with 0.5 mg of norethindrone acetate, P=.004 for 17-beta estradiol with 0.25 mg of norethindrone acetate, and P=.001 fo r 1 mg of 17-beta estradiol vs placebo). Compared with unopposed 17-beta es tradiol, 17-beta estradiol with 0.5 mg of norethindrone acetate enhanced th e reductions in total cholesterol and apolipoprotein B levels (P<.01 vs 17- <beta> estradiol). 17-beta Estradiol plus norethindrone blunted or reversed the increases in levels of high-density lipoprotein cholesterol, apolipopr otein A-I, and triglycerides produced by 17-beta estradiol alone. Effects o f 17-beta estradiol plus norethindrone on hemostatic variables were similar to those of 17-beta estradiol except for factor VII activity, which was si gnificantly reduced with 17-beta estradiol combined with 0.25 mg (P<.01) an d 0.5 mg (P<.05) of norethindrone acetate. 17-beta Estradiol plus norethind rone appeared to blunt reductions in C-peptide and insulin levels produced by unopposed 17-beta estradiol but did not elevate these values compared wi th placebo. Conclusions: 17-beta Estradiol plus norethindrone produced favorable change s in most cardiovascular risk markers evaluated and has a profile distinct from that of unopposed 17-beta estradiol. The impact of these differences o n cardiovascular events warrants investigation.