Effects of continuous combined hormone-replacement therapy on lipid levels in hypercholesterolemic postmenopausal women.

PURPOSE: To test the lipid-lowering effects of continuous combined hormone-replacement therapy in hypercholesterolemic postmenopausal women. PATIENTS AND METHODS: A total of 32 postmenopausal women identified through health fair and cholesterol screening records, whose ad libitum low-density lipoprotein (LDL) cholesterol level (mean of 2 measurements) was > 130 mg/dL, and whose fasting triglycerides were < 250 mg/dL, participated in a placebo-controlled, nonrandomized trial testing the lipid-lowering effect of continuous combined hormone-replacement therapy. Women with a history of uterine fibroids, thrombophlebitis, family or personal history of breast cancer, or recent hormone use were excluded. After a 1-month period to standardize baseline dietary intake (Hi-Sat), patients were taught a cholesterol-lowering, Step-One diet, which they followed for the remainder of the study. After 3 months, patients supplemented the Step-One diet with daily placebo tablets for 3 months, followed by supplementation with conjugated estrogens 0.625 mg/d plus medroxyprogesterone 2.5 mg/d for 3 months. The means of five fasting lipid and lipoprotein values at the end of each 3-month supplementation period were compared. RESULTS: Total cholesterol fell from 261 mg/dL to 250 mg/dL to 233 mg/dL, with LDL reduction from 181 mg/dL to 173 mg/dL to 150 mg/dL, on diet and diet plus continuous combined hormone-replacement therapy, respectively (all P < 0.05). Whereas 26 of the 32 women had LDL values above 160 mg/dL during the Hi-Sat diet, only 10 of the 32 women remained with LDL values in this range during Step-One diet plus hormone therapy. Besides improving LDL cholesterol levels, continuous combined hormone-replacement therapy was associated with an increase in high density lipoprotein (HDL) cholesterol levels from 51 mg/dL to 54 mg/dL (P < 0.05). The 2 women whose HDL cholesterol levels were < 35 mg/dL during the Step-One diet plus placebo achieved HDL cholesterol levels > 35 mg/dL during hormone therapy. Nevertheless, continuous combined hormone-replacement therapy was associated with a high frequency of side effects, including breast tenderness and uterine bleeding. Most bothersome side effects dissipated after an initial adjustment period. CONCLUSIONS: Continuous combined hormone-replacement therapy can produce significant and therapeutic reductions in LDL cholesterol levels in hypercholesterolemic postmenopausal women. After internists become familiar with the expected side effects and their time course, this regimen may provide an effective approach in the management of hypercholesterolemia in postmenopausal women who have not undergone hysterectomy.