Estrogen replacement therapy produces clinically important reductions in low-density lipoprotein (LDL) cholesterol concentrations and increases in levels of high-density lipoprotein (HDL) cholesterol. Observational studies have shown a reduction in the incidence of atherosclerotic cardiovascular disease as a result of estrogen replacement therapy. Davidson and associates compared the effects of estrogen replacement therapy and pravastatin in postmenopausal women with hypercholesterolemia.

A total of 76 women with LDL levels greater than 150 mg per dL (3.9 mmol per L) were randomly assigned to one of four treatment groups: conjugated estrogen (0.625 mg per day); pravastatin (20 mg per day); conjugated estrogen (0.625 mg per day) plus pravastatin (20 mg per day); or placebo. The length of the study was 16 weeks. Primary end points in the double-blind, placebo-controlled study were changes in the serum lipid levels.

Levels of non-HDL cholesterol decreased significantly compared with placebo in all three treatment groups: a decrease of 13.0 percent in the estrogen-only group, 23.7 percent in the pravastatin group and 25.2 percent in the estrogen–pravastatin group. The difference between the pravastatin and combined treatment groups was not significant.

HDL cholesterol levels rose significantly in both estrogen groups. In the estrogen-only group, HDL cholesterol levels rose 22.5 percent. In the estrogen–pravastatin group, they increased by 21.2 percent. A nonsignificant increase (3.7 percent) in HDL cholesterol occurred in the pravastatin group, and a slight decrease (3.3 percent) was noted in the placebo group.

Examination of the values for the combined treatment group showed that the non-HDL cholesterol and HDL cholesterol responses were most significant at week 4, after which the levels tended to drift toward baseline. After 16 weeks of treatment, the mean non-HDL cholesterol value in the estrogen–pravastatin group had stabilized and was near that of the pravastatin group, while the mean HDL cholesterol level had stabilized and was close to that of the estrogen-only group.

Triglyceride levels increased by 11.3 percent in the placebo group, as compared with baseline levels. They remained similar to baseline levels in the combined treatment group and the pravastatin group. These changes were significantly different from that of the placebo group, but not different from one another.

Results of this study support the National Cholesterol Education Program recommendation that consideration be given to administering estrogen replacement therapy to post-menopausal women with elevated LDL cholesterol levels.

When estimates of coronary event reduction were calculated according to the percentage of increase in HDL cholesterol levels and decrease in non-HDL cholesterol levels, the predicted risk reduction would be 40 to 50 percent in the estrogen-only and pravastatin-only groups and 60 to 70 percent in the estrogen–pravastatin group.

The authors point out that the price of estrogen replacement therapy is substantially lower than the price of therapy with an HMG-CoA reductase inhibitor. Therefore, the cost savings associated with use of estrogen as a first-line pharmacologic therapy for post-menopausal women with mild to moderate hypercholesterolemia could be substantial. Since approximately 33 percent of American women have undergone hysterectomy by the age of 60, a substantial number of women would be candidates for unopposed estrogen therapy. For women who have not undergone hysterectomy, a progestin would be added to the estrogen therapy.

The authors conclude that conjugated estrogen in a dosage of 0.625 mg per day is effective in lowering LDL cholesterol and increasing HDL cholesterol levels in postmenopausal women with hypercholesterolemia. When estrogen was combined with pravastatin, the serum lipid profile appeared to be altered more favorably than with either agent alone.