Hormone replacement and simvastatin in the therapy of hypercholesterolemicpostmenopausal women

Objectives: To prospectively investigate the effect of cholesterol lowering diet, hormone replacement therapy and simvastatin on plasma lipid levels u sing a 3-month stepwise protocol. Methods: Participants were postmenopausal women under the age of 60 with hy percholesterolemia (plasma total cholesterol> 240mg/dl). The study started with 3 months of Step-One diet (phase I) followed by 3 months of diet and h ormone replacement therapy (0.625mg conjugated estrogens daily combined wit h 5mg medroxyprogesterone acetate at days 13-25 of each cycle) (phase II). In women whose total cholesterol remained above 240mg/dl or LDL-cholesterol above 160mg/dl by the end of phase II, simvastatin at 10mg 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 satisfactor y cholesterol levels by the end of 6 months. Another 25 patients (33%) drop ped out of the study for Various reasons by that time. In the 34 patients w ho started simvastatin, plasma total cholesterol levels did not significant ly change during phase I and II, however, LDL-cholesterol significantly dec reased (204+/-31 to 187+/-26mg/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-cho lesterol levels after one month of phase III (281+/-26 to 213+/-30mg/dl 187 +/-26 to 122+/-30mg/dl respectively, p<0.0001), with no further changes dur ing the rest of the study period. No significant changes occurred in HDL-ch olesterol and triglyceride plasma levels at this phase. Adverse effects wer e few and minor throughout the study. Conclusions: Some of the hypercholesterolemic 'postmenopausal women will be nefit from hormone replacement therapy as a single cholesterol lowering tre atment in addition to diet (21% in our series). Nevertheless, combination t herapy of estrogens and low dose simvastatin proved to be extremely effecti ve in lowering cholesterol levels with no significant side effects. Such th erapeutic regimen may also have a synergistic antiatherogenic effect.