title: 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 >/= 45 years, with amenorrhea from 6 to 60 months (mean, 1.9 +/- 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] < 75 mg/dL, and triglycerides < 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 microg 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-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 (-62 mg/dL [-20%] and -72 mg/dL [-30%], respectively), CEE (-42 mg/dL [-13%] and -45 mg/dL [-18%]), and ETP (-30 mg/dL [-10%] and -26 mg/dL [-11%]) groups compared to baseline, but only simvastatin showed an effect significantly superior to diet alone. Apolipoprotein (Apo) B was decreased by simvastatin (-25%, P <.001) and by CEE (-10%, P <.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 (-17%); lipoprotein[a] (Lp[a]) was decreased by both HRTs (-38%, P <.05, and -22%, P =.07, for CEE and ETP, respectively). Among coagulative parameters, plasminogen activator inhibitor-1 (PAI-1) was significantly reduced by CEE (-29%, P <.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.
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Internal Medicine II, and the Menopause and Osteoporosis Center, University of Ferrara, Ferrara, Italy.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Vigna
authors.forename: Paola
authors.initials: P
authors.lastname: Donegà
authors.forename: Rosanna
authors.initials: R
authors.lastname: Zanca
authors.forename: Angela
authors.initials: A
authors.lastname: Barban
authors.forename: Angelina
authors.initials: A
authors.lastname: Passaro
authors.forename: Francesco
authors.initials: F
authors.lastname: Pansini
authors.forename: Gloria
authors.initials: G
authors.lastname: Bonaccorsi
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Mollica
authors.forename: Renato
authors.initials: R
authors.lastname: Fellin
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D000990:Antithrombin III / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015914:Estrogen Replacement Therapy / Q000379:methods; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006710:Homocysteine / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008055:Lipids / Q000097:blood*; D017270:Lipoprotein(a) / Q000097:blood; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D017698:Postmenopause; D011372:Progestins / Q000008:administration & dosage; D019821:Simvastatin / Q000008:administration & dosage*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004966:Estrogens, Conjugated (USP); D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D017270:Lipoprotein(a); D017395:Plasminogen Activator Inhibitor 1; D011372:Progestins; D014280:Triglycerides; D006710:Homocysteine; D000990:Antithrombin III; D005340:Fibrinogen; D019821:Simvastatin