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Individual and combined effects of estrogen/progestin therapy and lovastatin on lipids and flow-mediated vasodilation in postmenopausal women with coronary artery disease.

Author(s): Herrington DM, Werbel BL, Riley WA, Pusser BE, Morgan TM

Affiliation(s): Department of Internal Medicine/Cardiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1045, USA. dherring@wfubmc.edu

Publication date & source: 1999-06, J Am Coll Cardiol., 33(7):2030-7.

Publication type: Clinical Trial; Randomized Controlled Trial

OBJECTIVES: We sought to examine the individual and combined effects of estrogen/progestin therapy versus lovastatin on lipids and flow-mediated vasodilation in postmenopausal women with heart disease. BACKGROUND: Little information is available regarding the relative benefits of estrogen replacement therapy versus reductase inhibitors and the potential utility of their combination as lipid-lowering therapy for postmenopausal women. METHODS: We conducted a randomized, double-blind, crossover trial in 24 postmenopausal women, each of whom received the following drug regimens during three consecutive six-week treatment periods: 1) hormone replacement (oral dose of 0.625 mg/day conjugated equine estrogens and 2.5 mg/day medroxyprogesterone acetate); 2) 20 mg lovastatin/day and 3) hormone replacement plus lovastatin. RESULTS: Total and low density lipoprotein (LDL) cholesterol were significantly lowered and high density lipoprotein (HDL) cholesterol was significantly increased by all three regimens compared with baseline (p < 0.05). Lovastatin was more effective than estrogen/progestin in reducing LDL (p < 0.001), but estrogen/progestin was slightly more effective in increasing HDL. The hormone replacement and lovastatin regimen blocked the estrogen-associated increase in triglycerides. Hormone replacement (alone and with lovastatin) resulted in increases in brachial artery flow-mediated vasodilator capacity (p = 0.01 for both regimens) and the area under the curve (p = 0.016 and p = 0.005, respectively) compared with baseline. Percent dilation was greatest after the hormone replacement regimen, whereas the area under the curve was greatest after hormone replacement plus lovastatin (69% improvement vs. baseline). CONCLUSIONS: In postmenopausal women with coronary disease and hyperlipidemia, conjugated equine estrogen produced significant improvements in lipids and vasodilator responses despite the concurrent administration of low dose medroxyprogesterone acetate. Low dose lovastatin produced greater reductions in LDL, but less dramatic improvements in vasodilator responses. Estrogen/progestin plus lovastatin may provide additional benefits via a greater reduction in the LDL/HDL ratio and attenuation of estrogen-associated hypertriglyceridemia. More information is needed about the safety and efficacy of such combinations of hormone replacement and reductase inhibitor therapy.

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