Hormone replacement and simvastatin in the therapy of hypercholesterolemic postmenopausal women.

OBJECTIVES: To prospectively investigate the effect of cholesterol lowering diet, hormone replacement therapy and simvastatin on plasma lipid levels using a 3-month stepwise protocol. METHODS: Participants were postmenopausal women under the age of 60 with hypercholesterolemia (plasma total cholesterol > 240 mg/dl). The study started with 3 months of Step-One diet (phase I) followed by 3 months of diet and hormone replacement therapy (0.625 mg conjugated estrogens daily combined with 5 mg medroxyprogesterone acetate at days 13-25 of each cycle) (phase II). In women whose total cholesterol remained above 240 mg/dl or LDL-cholesterol above 160 mg/dl by the end of phase II, simvastatin at 10 mg daily was added (phase III). Plasma cholesterol levels as well as safety measurements were closely monitored. RESULTS: Sixteen (21%) of 75 patients who entered the study had satisfactory cholesterol levels by the end of 6 months. Another 25 patients (33%) dropped out of the study for various reasons by that time. In the 34 patients who started simvastatin, plasma total cholesterol levels did not significantly change during phase I and II, however, LDL-cholesterol significantly decreased (204 +/- 31 to 187 +/- 26 mg/dl, p = 0.04) and HDL increased (53 +/- 12 to 62 +/- 16 mg/dl, p = 0.04). A dramatic decrease occurred in both total and LDL-cholesterol levels after one month of phase III (281 +/- 26 to 213 +/- 30 mg/dl 187 +/- 26 to 122 +/- 30 mg/dl respectively, p < 0.0001), with no further changes during the rest of the study period. No significant changes occurred in HDL-cholesterol and triglyceride plasma levels at this phase. Adverse effects were few and minor throughout the study. CONCLUSIONS: Some of the hypercholesterolemic postmenopausal women will benefit from hormone replacement therapy as a single cholesterol lowering treatment in addition to diet (21% in our series). Nevertheless, combination therapy of estrogens and low dose simvastatin proved to be extremely effective in lowering cholesterol levels with no significant side effects. Such therapeutic regimen may also have a synergistic anti-atherogenic effect.