EFEITO DO RALOXIFENO SOBRE A HOMOCISTEINA DEPENDE DOS NIVEIS PLASMATICOS DO AMINOACIDO





EFEITO DO RALOXIFENO SOBRE A HOMOCISTEINA DEPENDE DOS NIVEIS PLASMATICOS DO AMINOACIDO

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O raloxifeno na pós-menopausa melhora o perfil lipídico e seu efeito redutor sobre a homocisteína é mais favorável nas pacientes com níveis basais elevados do aminoácido.
carvalhomarcia9.jpg Autor:
Márcia Neves Carvalho
Columnista Experto de SIIC
Artículos publicados por Márcia Neves Carvalho
Coautores
George Dantas Azevedo* José Ernesto Santos* Rui Alberto Ferriani* Gustavo Salata Romão* Marcos Felipe Silva de Sá* 
Professor Doutor, São Paulo, Brasil*
Recepción del artículo
17 de Diciembre, 2006
Aprobación
31 de Enero, 2007
Primera edición
1 de Junio, 2007
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
Objetivos: Avaliar os efeitos do raloxifeno sobre a concentração plasmática de homocisteína e o lipidograma em mulheres na pós-menopausa. Métodos: Foram estudadas 33 mulheres saudáveis na pós-menopausa, com idade entre 50 e 70 anos e diagnóstico de osteopenia e/ou osteoporose: 24 foram submetidas à terapia com raloxifeno, 60 mg/dia, durante seis meses e nove fizeram parte do grupo-controle. Foram dosados a homocisteína plasmática antes do início e após três e seis meses de tratamento, além do colesterol total, HDL-colesterol, LDL-colesterol e triglicérides. Resultados: Observamos redução significativa do colesterol total (227.6 ± 56.3 vs 200.6 ± 29.8 vs 192.8 ± 32.1 mg/dl; p < 0.001) e do LDL-colesterol (151.4 ± 46.3 vs 122.7 ± 29.4 vs 119.0 ± 28.6 mg/dl; p < 0.001), aumento significativo do HDL-colesterol (44.7 ± 10.8 vs 52.2 ± 12.6 vs 49.0 ± 10.8 mg/dl; p < 0.05) e nenhuma alteração significativa dos triglicérides no grupo tratado. No grupo controle não houve modificação em nenhum desses parâmetros. Embora não significativa, foi observada redução da homocisteína de 4.5% entre os períodos pré e pós-tratamento com raloxifeno, com uma correlação significativa entre os níveis basais e os percentuais de redução após o tratamento (r = 0.72; p < 0.001). Não observamos alteração significativa da homocisteina ou qualquer correlação entre a queda e os níveis basais no grupo-controle. Conclusões: A terapia com raloxifeno, 60 mg/dia, em mulheres na pós-menopausa durante seis meses, melhora o perfil lipídico e o seu efeito de redução sobre os níveis de homocisteína é mais favorável nas pacientes com níveis basais elevados do aminoácido.

Palabras clave
menopausa, doença cardiovascular, raloxifeno, homocisteína, perfil lipídico


Artículo completo

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Abstract
Objective: To evaluate the effects of raloxifene on the plasma concentration of homocysteine and on the lipid profile of postmenopausal women. Methods: Thirty-three healthy postmenopausal women aged 50 to 70 years with a diagnosis of osteopenia and/or osteoporosis were studied. Twenty-four were treated with raloxifene, 60 mg/day, for six months, and nine were used as untreated controls. Plasma homocysteine, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides were determined at the beginning and after three and six months of treatment. Results: We observed a significant reduction of total cholesterol (227.6 ± 56.3 vs 200.6 ± 29.8 vs 192.8 ± 32.1 mg/dl; p < 0.001) and LDL-cholesterol (151.4 ± 46.3 vs 122.7 ± 29.4 vs 119.0 ± 28.6 mg/dl; p < 0.001), a significant increase in HDL-cholesterol (44.7 ± 10.8 vs 52.2 ± 12.6 vs 49.0 ± 10.8 mg/dl; p < 0.05) and no significant change in triglycerides in the treated group. The control group showed no changes in any of these parameters. Although nonsignificant, a 4.5% reduction in homocysteine was observed between pre- and post-treatment with raloxifene, with a significant correlation between basal levels and percent reduction after treatment (r = 0.72; p < 0.001). There was no significant reduction in homocysteine or any correlation between basal and reduced levels in the control group. Conclusions: Treatment of menopausal women with raloxifene, 60 mg/day, for six months improved the lipid profile, and the effect of the drug on homocysteine levels was more favorable in patients with elevated basal levels of the amino acid.

Key words
menopause, cardiovascular disease, raloxifene, homocysteine, lipid profile


Clasificación en siicsalud
Artículos originales > Expertos de Iberoamérica >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: 
Relacionadas: Bioquímica, Endocrinología y Metabolismo, Farmacología, Obstetricia y Ginecología, Oncología



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Enviar correspondencia a:
Marcos Felipe Silva de Sá, Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, 14049-900, Av. Bandeirantes, 3900, Ribeirão Preto, Brasil
Bibliografía del artículo
1. Centers for Disease Control and Prevention. www.cdc.gov/nchs/hus.htm, 2004.
2. Welch GN, Loscalzo J. Homocysteine and atherothrombosis. N Engl J Med 338:1042-50, 1998.
3. Mudd SH, Levy HL, Skovby F. Disorders of transsulfuration. The metabolic basis of inherited disease. 1st ed. New York: McGraw-Hill, pp. 693-734, 1989.
4. Jacobsen DW. Homocysteine and vitamins in cardiovascular disease. Clin Chem 44:1833-43, 1998.
5. Chambers JC, McGregor A, Jean-Marie J, Obeid OA, Kooner JS. Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia: an effect reversible with vitamin C therapy. Circulation 99:1156-60, 1999.
6. Nappo F, De Rosa N, Marfella R, e col. Impairment of endothelial functions by acute hyperhomocysteinemia and reversal by antioxidant vitamins. JAMA 281:2113-18, 1999.
7. Morris MS, Jacques PF, Selhub J, Rosenberg IH. Homocisteína total e indicadores da situação dos estrógenos no terceiro levantamento nacional de saúde e avaliação da nutrição (NHANES III). Am J Epidemiol 152:140-8, 2000.
8. Wouters MGAJ, Moorrees EC, Van der Mooren MJ, e col. Plasma homocysteine and menopausal status. Eur J Clin Invest 25:801-5, 1995.
9. Grady D, Herrington D, Bittner V, e col. Cardiovascular disease outcomes during 6.8 years of hormone therapy. Heart and Estrogen/Progestin Replacement Study Follow-up (HERS II). JAMA 288:49-57, 2002.
10. Rossouw JE, Anderson GL, Prentice RL, e col. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the Women's Health Initiative Randomized Controlled Trial. JAMA 288:321-33, 2002.
11. Ettinger B, Black DM, Mitlak BH, e col. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. JAMA 282:637-45, 1999.
12. Martino S, Cauley JA, Barrett-Connor E, e col. Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Nat Cancer Inst 96:1751-61, 2004.
13. Barrett-Connor E, Grady D, Sashegyi A, e col. Raloxifene and cardiovascular events in osteoporotic postmenopausal women. Four-year results from the MORE (Multiple Outcomes of Raloxifene Evaluation) randomized trial. JAMA 287:847-57, 2002.
14. Duvernoy CS, Kulkarni PM, Dowsett SA, Keech CA. Vascular events in the Multiple Outcomes of Raloxifene Evaluation (MORE) trial: incidence, patient characteristics, and effect of raloxifene. Menopause 12:444-52, 2005.
15. Martino S, Disch D, Dowsett SA, Keech CA, Mershon JL. Safety assessment of raloxifene over eight years in a clinical trial setting. Curr Med Res Opin 21:1441-51, 2005.
16. Barrett-Connor E, Mosca L, Collins P, Geiger MJ, Grady D, Kornitzer M, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 355:125-137, 2006.
17. Mijatovic V, Netelenbos C, Van der Mooren MJ, De Valk-De Roo GW, Jakobs C, Kenemans P. Randomized, double-bind, placebo-controlled study of the effects of raloxifene and conjugated equine estrogen on plasma homocysteine levels in healthy postmenopausal women. Fertil Steril 70:1085-89, 1998.
18. Walsh BW, Paul S, Wild RA, e col. The effects of hormone replacement therapy and raloxifene on C-reactive protein and homocysteine in healthy postmenopausal women: a randomized, controlled trial. J Clin Endocrin Metab 85:214-8, 2000.
19. Smolders RGV, Vogelvang TE, Mijatovic V, e col. A 2-year, randomized, comparative, placebo-controlled study on the effects of raloxifene on lipoprotein (a) and homocysteine. Maturitas 41:105-14, 2002.
20. Anderson A, Brattstrom L, Israelsson B, Isaksson A, Hamfelt A, Hultberg B. Plasma homocysteine before and after methionine loading with regard to age, gender, and menopausal status. Eur J Clin Invest 22:79-87, 1992.
21. Lufkin EG, Whitaker MD, Nickelsen T, e col. Treatment of established postmenopausal osteoporosis with raloxifene: a randomized trial. J Bone Miner Res 13:1747-54, 1998.
22. Walsh BW, Kuller LH, Wild RA, e col. Effects of raloxifene on serum lipids and coagulation factors in healthy postmenopausal women. JAMA 279:1445-51, 1998.
23. Nichelsen T, Creatsas G, Rechberger T, e col. Differential effects of raloxifene and continuous combined hormone replacement therapy on biochemical markers of cardiovascular risk: results from the Euralox 1 study. Climateric 4:320-31, 2001.
24. Francucci CM, Daniele P, Iori N, Camilletti A, Massi F, Boscaro M. Effects of raloxifene on body fat distribution and lipid profile in healthy post-menopausal women. J Endocrinol Invest 28:623-31, 2005.
25. Barrett-Connor E, Ensrud KE, Harper K, e col. Post Hoc analysis data from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial on the effects of three years of raloxifene treatment on glycemic control and cardiovascular disease risk factors in women with and without type 2 diabetes. Clin Ther 25:919-30, 2003.
26. Jolly EE, Bjarnason NH, Neven P, e col. Prevention of osteoporosis and uterine effects in postmenopausal women taking raloxifene for 5 years. Menopause 10:337-44, 2003.
27. Eikelboom JW, Lonn E, Genest J Jr, Hankey G, Yusuf S. Homocysteine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med 131:363-75, 1999.
28. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA 274:1049-57, 1995.
29. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 325:1202, 2002.
30. Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG. MTHFR 677 (rightarrow) T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA 288:2023-31, 2002.
31. The Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 288:2015-22, 2002.
32. Rees MM, Rodgers GM. Homocysteinemia: association of a metabolic disorder with vascular disease and thrombosis. Thromb Res 71:337-59, 1993.
33. Harpel PC, Zhang X, Borth W. Homocysteine and hemostasis: pathogenic mechanisms predisposing to thrombosis. J Nutr 126:1285S-9S, 1996.
34. Tawakol A, Omland T, Gerhard M, Wu JT, Creager MA. Hyperhomocyst(e)inemia is associated with impaired endothelium-dependent vasodilation in humans. Circulation 95:1119-21, 1997.
35. Lonn E, Yusuf S, Arnold MJ, e col. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 354:1567-77, 2006.
36. Bonaa KH, Inger N, Ueland PM, e col. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 354:1578-88, 2006.
37. Vogelvang TE, Mijatovic V, Kenemans P, Teerlink T, van der Mooren MJ. HMR 3339, a novel selective estrogen receptor modulator, reduces total cholesterol, low-density lipoprotein cholesterol, and homocysteine in healthy postmenopausal women. Fertil Steril 82(6):1540-9, 2004.
38. De Leo V, La Marca A, Morgante G, Lanzetta D, Setacci C, Petraglia F. Randomized control study of the effects of raloxifene on serum lipids and homocysteine in older women. Am J Obstet Gynec 184:350-3, 2001.
39. Christodoulakos G, Lambrinoudaki I, Panoulis C, Rizos D, Coutoukos J, Creatsas G. Effect of raloxifene, estrogen, and hormone replacement therapy on serum homocysteine levels in postmenopausal women. Fertil Steril 79:455-6, 2003.
40. Gol M, Akan P, Dogan E, Karas C, Saygili U, Posaci C. Effects of estrogen, raloxifene, and hormona peplacement therapy on serum C-reactive protein and homocysteine levels. Maturitas 53:252-9, 2006.
41. Griffiths KA, Sader MA, Skilton MR, Harmer JA, Celermajer DS. Effects of raloxifene on endothelium-dependent dilation, lipoproteins, and markers of vascular function in postmenopausal women with coronary artery disease. JACC 42:698-704, 2003.
42. Cerquetani E, Vitale C, Mercuro G, Fini M, Zoncu S, Rosano GM. Comparative vascular effects of hormone replacement therapy and raloxifene in women at increased cardiovascular risk. Gynecol Endocrinol 18:291-8, 2004.

 
 
 
 
 
 
 
 
 
 
 
 
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