Health> Vol.5 No.7D, July 2013

Oral low-dose estradiol plus norethisterone acetate with or without simvastatin in dyslipidemic and symptomatic menopausal women: A randomized clinical trial

DownloadDownload as PDF (Size:380KB)  HTML    PP. 110-118  

ABSTRACT

Context and Objective: Cardiovascular diseases are the leading causes of death in postmenopausal women and dyslipidemia has important contributing factor. The objective of the study was to evaluate low-dose estrogen plus progestogen therapy (EPT) + simvastatin for vasomotor symptoms and lipid and lipoprotein profiles. Design and Setting: Clinical trial was conducted in a private clinical research center. Methods: Two hundred forty symptommatic postmenopausal women with dyslipidemia were randomized to one of three treatment groups: A) 1 mg estradiol/ 0.5 mg norethisterone acetate (E2/NETA) + 20 mg simvastatin; B) E2/NETA + placebo; or C) 20 mg simvastatin + placebo. Lipid and lipoprotein profiles and menopausal symptoms were evaluated after 16 weeks. Results: Total cholesterol, LDL cholesterol, non-HDL cholesterol decreased (P < 0.05) in all three groups, Apo-B/Apo-A1 and ApoB (P < 0.01) in groups A and C and TG and ApoA1 only in group A comparing baseline versus final. Comparing the groups, group B showed differences in relation to others in total cholesterol, non-HDL cholesterol, LDL cholesterol, Apo B and ApoB/Apoa1 (P < 0.01). Relief of menopausal symptoms was better compared in A and B. Conclusions: Thus in postmenopausal women with dyslipidemia, the association of E2/ NETA low-dose with simvastatin relieved climacteric symptoms similar to that observed with isolated E2/NETA and improved lipid and lipoprotein profile similar to the isolated use of simvastatin. The use of E2/NETA alone decreased menopausal symptoms, but did not improve dyslipidemia.

Cite this paper

Steiner, M. , Pompei, L. , Strufaldi, R. , Cunha, E. and Fernandes, C. (2013) Oral low-dose estradiol plus norethisterone acetate with or without simvastatin in dyslipidemic and symptomatic menopausal women: A randomized clinical trial. Health, 5, 110-118. doi: 10.4236/health.2013.57A4016.

References

[1] Mosca, L., Collins, P., Herrington, D.M., et al. (2001) Hormone replacement therapy and cardiovascular disease: A statement for health care professionals from the American Heart Association. Circulation, 104, 499-503. doi:10.1161/hc2901.092200
[2] Herrington, D.M., Reboussin, D.M., Brosnihan, K.B., et al. (2000) Effects of estrogen replacement on the progression of coronary-artery atherosclerosis. New England Journal of Medicine, 343, 522-529. doi:10.1056/NEJM200008243430801
[3] Humphrey, L.L., Chan, B.K. and Sox, H.C. (2002) Postmenopausal hormone replacement therapy and the primary prevention of cardiovascular disease. Annals of Internal Medicine, 137, 273-284. doi:10.7326/0003-4819-137-4-200208200-00012
[4] Grady, D., Rubin, S.M., Petitti, D.B., et al. (1992) Hormone therapy to prevent disease and prolong life in postmenopausal women. Annals of Internal Medicine, 117, 1016-1037. doi:10.7326/0003-4819-117-12-1016
[5] Hulley, S., Grady, D., Bush, T., et al. (1998) Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Gorup. JAMA, 280, 605-613. doi:10.1001/jama.280.7.605
[6] Manson, J.E., Hsia, J., Johnson, K.C., et al. (2003) Estrogen plus progestin and the risk of coronary heart disease. New England Journal of Medicine, 349, 523-534. doi:10.1056/NEJMoa030808
[7] Rossouw, J.E. (2006) Implications of recent clinical trials of postmenopausal hormone therapy for management of cardiovascular disease. Annals of the New York Academy of Sciences, 1089, 444-453. doi:10.1196/annals.1386.046
[8] LaRosa, J.C., He, J. and Vupputuri, S. (1999) Effect of statins on risk of coronary disease: A meta-analysis of randomized controlled trials. JAMA, 282, 2340-2346. doi:10.1001/jama.282.24.2340
[9] Downs, J.R., Clearfield, M., Weis, S., et al. (1998) Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: Results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA, 279, 1615-1622. doi:10.1001/jama.279.20.1615
[10] Herd, J.A., Ballantyne, C.M., Farmer, J.A., et al. (1997) Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]). American Journal of Cardiology, 80, 278-286. doi:10.1016/S0002-9149(97)00346-9
[11] Heart Protection Study Collaborative Group (2002) MRC/ BHF heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: A randomized placebo-controlled trial. Lancet, 360, 7-22. doi:10.1016/S0140-6736(02)09327-3
[12] (1994) Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: The Scandinavian Simvastatin Survival Study (4S). Lancet, 344, 1383-1385.
[13] Darling, G.M., Johns, J.A., McCloud, P.I. and Davis, S.R. (1999) Concurrent use of simvastatin and estrogen-progestin therapy compared with each therapy alone for hypercholesterolemia in postmenopausal women. Climacteric, 2, 181-188. doi:10.3109/13697139909038060
[14] Vigna, G.B., Donegà, P., Zanca, R., et al. (2002) Simvastatin, transdermal patch, and oral estrogen-progestogen preparation in early-postmenopausal hypercholesterolemic women: A randomized, placebo-controlled clinical trial. Metabolism, 51, 1463-1470. doi:10.1053/meta.2002.35584
[15] Fak, A.S., Erenus, M., Tezcan, H., et al. (2000) Effects of simvastatin only or in combination with continuous combined hormone replacement therapy on serum lipid levels in hypercholesterolaemic post-menopausal women. European Heart Journal, 21, 190-197. doi:10.1053/euhj.1999.1582
[16] Darling, G.M., Johns, J.A., McCloud, P.I. and Davis, S.R. (1997) Estrogen and progestin compared with simvastatin for hypercholesterolemia in postmenopausal women. New England Journal of Medicine, 337, 595-601. doi:10.1056/NEJM199708283370903
[17] Hsia, J., Langer, R.D., Manson, J.E., et al. (2006) Conjugated equine estrogens and coronary heart disease: The Women’s Health Initiative. Archives of Internal Medicine, 166, 357-365. doi:10.1001/archinte.166.3.357
[18] Dupont, W.D. and Plummer, W.D. (1997) PS power and sample size program available for free on the internet. Control Clinical Trials, 18, 274. doi:10.1016/S0197-2456(97)00074-3
[19] Davis, S.R., Goldstat, R., Newman, A., et al. (2002) Differing effects of low-dose estrogen-progestin therapy and pravastatin in postmenopausal hypercholesterolemic women. Climacteric, 5, 341-350.
[20] Samsioe, G., Li, C., Borgfeldt, C., et al. (2002) Changes in lipid and lipoprotein profile in postmenopausal women receiving low-dose combinations of 17 beta-estradiol and norethisterone acetate. Menopause, 9, 335-342. doi:10.1097/00042192-200209000-00006
[21] Koh, K.K., Cardillo, C., Bui, M.N., et al. (1999) Vascular effects of estrogen and cholesterol-lowering therapies in hypercholesterolemic postmenopausal women. Circulation, 99, 354-360. doi:10.1161/01.CIR.99.3.354
[22] Rossouw, J.E., Prentice, R.L., Manson, J.E., Wu, L., Barad, D., Barnabei, V.M. et al. (2007) Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA, 297, 1465-1477. doi:10.1001/jama.297.13.1465
[23] Davidson, M.H., Maki, K.C., Marx, P., et al. (2000) Effects of continuous estrogen and estrogen-progestin replacement regimens on cardiovascular risk markers in postmenopausal women. Archives of Internal Medicine, 160, 3315-3325. doi:10.1001/archinte.160.21.3315
[24] The Lipid Research Clinics Coronary Primary Prevention (1984) Trial results: I. Reduction in incidence of coronary heart disease. JAMA, 251, 351-364. doi:10.1001/jama.1984.03340270029025
[25] Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001) Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA, 285, 2486-2497. doi:10.1001/jama.285.19.2486
[26] Ingelsson, E., Schaefer, E.J., Contois, J.H., et al. (2007) Clinical utility of different lipid measures for prediction of coronary heart disease in men and women. JAMA, 298, 776-785. doi:10.1001/jama.298.7.776
[27] Al-Azzawi, F., Wahab, M., Sami, S., et al. (2004) Randomized trial of effects of estradiol in combination with either norethisterone acetate or trimegestone on lipids and lipoproteins in postmenopausal women. Climacteric, 7, 292-300. doi:10.1080/13697130400001364
[28] Walldius, G. and Jungner, I. (2006) The apoB/apoA-I ratio: A strong, new risk factor for cardiovascular disease and a target for lipid-lowering therapy—A review of the evidence. Journal of Internal Medicine, 259, 493-519. doi:10.1111/j.1365-2796.2006.01643.x
[29] Yusuf, S., Hawken, S., Ounpuu, S., et al. (2004) Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the Interheart study): Case-control study. Lancet, 364, 937-952. doi:10.1016/S0140-6736(04)17018-9
[30] Sierra-Johnson, J., Fisher, R.M., Romero-Corral, A., et al. (2009) Concentration of apolipoprotein B is comparable with the apolipoprotein B/apolipoprotein A-I ratio and better than routine clinical lipid measurements in predicting coronary heart disease mortality: Findings from a multi-ethnic US population. European Heart Journal, 30, 710-717. doi:10.1093/eurheartj/ehn347
[31] Maclennan, A.H., Broadbent, J.L., Lester, S. and Moore, V. (2004) Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database of Systematic Reviews, 4, CD002978.

  
comments powered by Disqus

Copyright © 2014 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.