Simvastatin, transdermal patch, and oral estrogen-progestogen preparation in early-postmenopausal hypercholesterolemic women: A randomized, placebo-controlled clinical trial

Abstract Hormone replacement therapy (HRT) seems to have a favorable influence on the plasma lipid profile. Only a few investigations have examined the effects of HRT versus hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors. We compared the relative effects of different hypolipidemic strategies on lipoproteins and coagulative parameters in women with recent-onset spontaneous menopause. In this 24-week, placebo-controlled trial, 60 consecutive healthy women aged [ge ] 45 years, with amenorrhea from 6 to 60 months (mean, 1.9 [plusmn] 1.4 years), serum follicle stimulating hormone (FSH) greater than 40 U/L, and slight to moderate hypercholesterolemia (low-density lipoprotein-cholesterol [LDL-C] 160 to 250 mg/dL, high-density lipoprotein-cholesterol [HDL-C] [lt ] 75 mg/dL, and triglycerides [lt ] 200 mg/dL) were enrolled and randomized to dietetic advice (placebo group), simvastatin 10 mg, 0.625 mg of conjugated equine estrogen (CEE), or 50 [mu ]g estrogen transdermal patch (ETP). In the latter 2 cases, the progestative nomegestrol was added to estrogens (days 17 to 28 of the cicle). Lipoprotein parameters were evaluated after separating very[ndash ]low-density lipoproteins (VLDLs) by ultracentrifugation, while fasting glucose and insulin, homocysteine, and hemocoagulative parameters were determined in plasma. Fifty-four patients completed the trial. Total cholesterol (TC) and LDL-C significantly decrased in the simvastatin ([minus ]62 mg/dL [[minus ]20%] and [minus ]72 mg/dL [[minus ]30%], respectively), CEE ([minus ]42 mg/dL [[minus ]13%] and [minus ]45 mg/dL [[minus ]18%]), and ETP ([minus ]30 mg/dL [[minus ]10%] and [minus ]26 mg/dL [[minus ]11%]) groups compared to baseline, but only simvastatin showed an effect significantly superior to diet alone. Apolipoprotein (Apo) B was decreased by simvastatin ([minus ]25%, P [lt ] .001) and by CEE ([minus ]10%, P [lt ] .05); again, simvastatin was more effective than either diet or ETP. Triglyceride concentration and VLDL-C were unmodified by treatments. HDL-C and Apo A-I significantly increased in the simvastatin group (+18% and +8%, respectively), while HDL-C was unmodified by both HRT regimens and Apo A-I was reduced by ETP treatment ([minus ]17%); lipoprotein[a] (Lp[a]) was decreased by both HRTs ([minus ]38%, P [lt ] .05, and [minus ]22%, P = .07, for CEE and ETP, respectively). Among coagulative parameters, plasminogen activator inhibitor-1 (PAI-1) was significantly reduced by CEE ([minus ]29%, P [lt ] .05) but not ETP treatment (+16%, P = not significant), while fibrinogen, antithrombin, and homocysteine were unaffected by therapy. Thus, HRT, particularly CEE, seems well tolerated and moderately effective in improving the lipid pattern and, perhaps, the coagulative/fibrinolytic balance in postmenopausal hypercholesterolemic women; it may represent a therapeutic option in slightly dyslipidemic subjects. Statins are preferred in case of more severe disease.