Estrogen and progestin compared with simvastatin for hypercholesterolemia in postmenopausal women

Postmenopausal estrogen therapy has favorable effects on serum lipoproteins in women with normal serum lipid levels, but the effect of combined estrogen and progestin therapy on lipoproteins in women with hypercholesterolemia has not been determined, nor has it been directly compared with the effect of conventional lipid-lowering therapy.

In a randomized crossover trial, we studied 58 postmenopausal women with fasting serum total cholesterol levels greater than 250 mg per deciliter. Each woman received simvastatin (10 mg daily) for eight weeks and postmenopausal hormone therapy (up to 1.25 mg of conjugated equine estrogens daily, along with 5 mg of medroxyprogesterone acetate daily) for eight weeks, with an eight-week washout period between the two treatment phases.

At base line, the mean (+/-SD) cholesterol values were as follows: total cholesterol, 305+/-39 mg per deciliter; high-density lipoprotein (HDL) cholesterol, 62+/-19 mg per deciliter; and low-density lipoprotein (LDL) cholesterol, 217+/-39 mg per deciliter. For total cholesterol, the mean decrease with hormone therapy was 14 percent (95 percent confidence interval, 11 to 16 percent) and the mean decrease with simvastatin was 26 percent (95 percent confidence interval, 23 to 29 percent). For LDL cholesterol, the mean decrease was 24 percent (95 percent confidence interval, 20 to 28 percent) with hormone therapy and 36 percent (95 percent confidence interval, 32 to 40 percent) with simvastatin. The effect of simvastatin was significantly greater than that of hormone therapy (P<0.001). HDL cholesterol increased similarly with hormone therapy (mean increase, 7 percent; 95 percent confidence interval, 2 to 12 percent) and simvastatin (mean increase, 7 percent; 95 percent confidence interval, 4 to 10 percent). Triglyceride levels increased with hormone therapy (mean increase, 29 percent; 95 percent confidence interval, 15 to 42 percent) but decreased with simvastatin (mean decrease, 14 percent; 95 percent confidence interval, 8 to 20 percent). Lp(a) lipoprotein decreased with hormone therapy (mean decrease, 27 percent; 95 percent confidence interval, 20 to 34 percent), but not with simvastatin.

In postmenopausal women with hypercholesterolemia, therapy with estrogen plus progestin has beneficial effects on lipoprotein levels. Hormone therapy may be an effective alternative to treatment with simvastatin, especially in women with normal triglyceride levels.