Menopause, the cardiovascular risk factor homocysteine, and the effects of treatment

Treatments in Endocrinology

Volumn 3, Issue 6, 2004, Pages 393-400

  De Leo, Vincenzo ^a   La Marca, Antonio ^b   Morgante, Giuseppe ^a   Musacchio, Maria Concetta ^a   Luisi, Stefano ^a   Petraglia, Felice ^a  

^a UNIVERSITY OF SIENA   (Italy)

^b UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CONJUGATED ESTROGEN; CYANOCOBALAMIN; ESTRADIOL; ESTROGEN; FOLIC ACID; GESTAGEN; HOMOCYSTEINE; MEDROGESTONE; NORETHISTERONE ACETATE; PYRIDOXINE; RALOXIFENE; TAMOXIFEN;

AMINO ACID BLOOD LEVEL; AMINO ACID METABOLISM; ATHEROSCLEROSIS; BREAST CANCER; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CLINICAL TRIAL; DRUG EFFECT; DRUG EFFICACY; DRUG FORMULATION; DRUG MEGADOSE; ENZYME DEFICIENCY; EPIDEMIOLOGICAL DATA; ESTROGEN THERAPY; GENE MUTATION; GENETIC EPIDEMIOLOGY; HEART PROTECTION; HEREDITY; HUMAN; HYPERHOMOCYSTEINEMIA; ISCHEMIC HEART DISEASE; LIFESTYLE; LOW DRUG DOSE; MENOPAUSE; NUTRITIONAL STATUS; PATHOGENESIS; POSTMENOPAUSE; PRIMARY PREVENTION; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT; RISK BENEFIT ANALYSIS; RISK FACTOR; SECONDARY PREVENTION; SEX DIFFERENCE; STROKE; TREATMENT OUTCOME;

CARDIOVASCULAR DISEASES; ESTROGEN REPLACEMENT THERAPY; FEMALE; FOLIC ACID; HOMOCYSTEINE; HUMANS; MENOPAUSE; RISK FACTORS; VITAMIN B 12; VITAMIN B 6;

EID: 9144267767     PISSN: 11756349     EISSN: None     Source Type: Journal    
DOI: 10.2165/00024677-200403060-00007     Document Type: Review

References (107)

1. de la Calle M, Usandizaga R, Sancha M, et al. Homocysteine, folic acid and B-group vitamins in obstetrics and gynaecology. Eur J Obstet Gynecol Reprod Biol 2003; 107 (2): 125-34
2. Still RA, McDowell IF. Clinical implications of plasma homocysteine measurement in cardiovascular disease. J Clin Pathol 1998; 51: 183-8
3. Refsum H, Fiskerstrand T, Guttormsen AB, et al. Assessment of homocysteine status. J Inherit Metab Dis 1997; 20; 286-94
4. Mudd SH, Levy HL, Jenden DJ, et al. Disorders of trans-sulfuration. In: Scriver CR, Beaudet AL, Sly VS, et al., editors. The metabolic and molecular bases of inherited disease. New York (NY): McGraw-Hill, 2001
5. Finkelstein JD. Methionine metabolism in mammals. J Nutr Biochem 1990; 1: 228-37
6. Finkelstein JD. The metabolism of homocysteine: pathways and regulation. Eur J Pediatr 1998; 157: S40-4
7. Ueland PM, Refsum H, Stabler SP, et al. Total homocysteine in plasma or serum: methods and clinical applications. Clin Chem 1993; 39: 1964-79
8. Jenks DA, Matthews RG. Allosteric inhibition of methylenetetrahydrofolate reductase by adenosylmethionine. J Biol Chem 1987; 262: 2485-93
9. Selhub J, Miller JW. The pathogenesis of homocysteinemia: interruption of the coordinate regulation by S-adenosylmethionine of the remethylation and transsulfuration of homocysteine. Am J Clin Nutr 1992; 55: 131-8
10. Mudd SH, Skovby F, Levy HL, et al. The natural history of homocystinuria due to cystathionine beta-synthase deficiency. Am J Hum Genet 1985; 37: 1-31
11. Sardharwalla IB, Fowler B, Robins AJ, et al. Detection of heterozygotes for homocystinuria: study of sulphur-containing amino acids in plasma and urine after L-methionine loading. Arch Dis Child 1974; 49: 553-9
12. Ogier de Baulny H, Gerard M, Saudubray JM, et al. Remethylation defects: guidelines for clinical diagnosis and treatment. Eur J Pediatr 1998; 157: s77-83
13. Kang SS, Zhou J, Wong PW, et al. Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet 1988; 43: 414-21
14. Franco RF, Araujo AG, Guerreiro JF, et al. Analysis of the 677 C→T mutation of the methylenetetrahydrofolate reductase gene in different ethnic groups. Thromb Haemost 1998; 79: 119-21
15. Gudnason V, Stansbie D, Scott J, et al. C677T (thermolabile alanine/valine) polymorphism in methylenetetrahydrofolate reductase (MTHFR): its frequency and impact on plasma homocysteine concentration in different European populations. Atherosclerosis 1998; 136: 347-54
16. Stevenson RE, Scwartz CE, Du YZ, et al. Differences in methylenetetrahydrofolate reductase genotype frequencies, between whites and blacks. Am J Hum Genet 1997; 60: 229-30
17. Hegele RA, Tully C, Young TK, et al. V677 mutation of methylenetetrahydrofolate reductase and cardiovascular disease in Canadian Inuit. Lancet 1997; 349: 1221-2
18. Sacchi E, Tagliabue L, Duca F, et al. High frequency of the C677t mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in Northern Italy. Thromb Haemost 1997; 78: 963-4
19. Motulsky AG. Nutritional ecogenetics: homocysteine-related arteriosclerotic vascular disease, neural tube defects, and folic acids. Am J Hum Genet 1996; 58: 17-20
20. Vermaak WJ, Ubbink JB, Delport R, et al. Ethnic immunity to coronary heart disease? Atherosclerosis 1991; 89: 155-62
21. Ubbink JB, Delport R, Vermaak WJ. Plasma homocysteine concentrations in a population with a low coronary heart disease prevalence. J Nutr 1996; 126: 1254S-7S
22. Araki A, Sako Y. Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromatogr 1987; 422: 43-52
23. van der Mooren MJ, Woutre MG, Blom HJ, et al. Hormone replacement therapy may reduce high serum homocysteine in postmenopausal women. Eur J Clin Invest 1994; 24: 733-6
24. Boers GH, Smals AG, Trijbels FJ. Unique efficiency of methionine metabolism in premenopausal women may protect against vascular disease in the reproductive years. J Clin Invest 1983; 72: 1971-6
25. Andersson A, Hultberg B, Brattstrom L, et al. Decreased serum homocysteine in pregnancy. Eur J Clin Chem Clin Biochem 1992; 30: 377-9
26. Steegers-Theunissen RPM, Boers GHJ, Blom H, et al. Hyperhomocysteinemia and recurrent spontaneous abortion orabruptio placenta. Lancet 1992; 339: 1122-3
27. Laivuori H, Kaaja R, Turpeinen U, et al. Plasma homocysteine levels elevated and inversely related to insulin sensitivity in preeclampsia. Obstet Gynecol 1999; 93: 489-93
28. Selhub J, Jacques PF, Wilson PW, et al. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 1993; 270: 2693-8
29. Kang SS, Wong PWK, Norusis M. Homocysteinemia due to folate deficiency. Metabolism 1987; 36: 458-62
30. Nygard O, Nordrehaug JE, Refsum H, et al. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997; 337: 230-6
31. Nygard O, Refsum H, Ueland PM, et al. Coffee consumption and total plasma homocysteine: the Hordaland Homocysteine Study. Am J Clin Nutr 1997; 65: 136-43
32. Nygard O, Refsum H, Ueland PM, et al. Major lifestyle determinants of plasma total homocysteine distribution: the Hordaland Homocysteine Study. Am J Clin Nutr 1998; 67: 263-70
33. Hultberg B, Berglund M, Andersson A, et al. Elevated plasma homocysteine in alcoholics. Alcohol Clin Exp Res 1993; 17: 687-9
34. 6 status. Am J Clin Nutr 1996; 63: 220-4
35. Barak AJ, Beckenhauer HC, Tuma DJ. Betaine, ethanol, and the liver: a review. Alcohol 1996; 13: 395-8
36. Hidiroglou N, Camillo ME, Beckenhauer HC, et al. Effect of chronic alcohol ingestion on hepatic folate distribution in the rat. Biochem Pharmacol 1994; 47: 1561-6
37. Gloria L, Cravo M, Camillo ME, et al. Nutritional deficiencies in chronic alcoholics: relation to dietary intake and alcohol consumption. Am J Gastroenterol 1997; 92: 485-9
38. Bostom AG, Lathrop L. Homocysteinemia in end-stage renal disease: prevalence, etiology, and potential relationship to arteriosclerotic outcomes. Kidney Int 1997; 52: 10-20
39. Refsum H, Wesenberg F, Ueland PM. Plasma homocysteine in children with acute lymphoblastic leukemia: changes during a chemotherapeutic regimen including methotrexate. Cancer Res 1991; 51: 828-35
40. McDonald CJ, Calabresi P. Psoriasis and occlusive vascular disease. Br J Dermatol 1978; 99: 469-75
41. Nedrebo BG, Ericsson UB, Nygard O, et al. Plasma total homocysteine in hyperthyroid and hypothyroid patients. Metabolism 1998; 47: 89-93
42. McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arterioscerosis. Am J Pathol 1969; 56: 111-28
43. Wilcken DEL, Wilcken B. The pathogenesis of coronary artery disease: a possible role for methionine metabolism. J Clin Invest 1976; 57: 1079-82
44. Arnesen E, Refsum H, Bonaa KH, et al. Serum total homocysteine and coronary heart disease. Int J Epidemiol 1995; 24: 704-9
45. Boushey CJ, Beresford SA, Omenn GS. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. JAMA 1995; 274: 1049-57
46. Graham IM, Daly LE, Refsum HM. Plasma homocysteine as a risk factor for vascular disease. JAMA 1997; 277: 1775-81
47. Rubbanyi GM. The role of the endothelium in cardiovascular homeostasis and diseases. J Cardiovasc Pharmacol 1993; 22: S1-14
48. De Meyer GR, Herman AG. Vascular endothelial dysfunction. Prog Cardiovasc Dis 1997; 39: 325-42
49. van der Molen EF, Hiipakka MJ, van Lith-Zanders H. Homocysteine metabolism in endothelial cells of a patient homozygous for cystathionine beta-synthase deficiency. Thromb Haemost 1997; 78: 827-33
50. Lentz SR, Sobey CG, Piegors DJ. Vascular dysfunction in monkeys with diet-induced hyperhomocysteinemia. J Clin Invest 1996; 98: 24-9
51. Cines DB, Pollak ES, Buck CA. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998; 91: 3527-61
52. Celermajer DS, Sorensen K, Ryalls M. Impaired endothelial function occurs in the systemic arteries of children with homozygous homocystinuria but not in their heterozygous parents. J Am Coll Cardiol 1993; 22: 854-8
53. Tawakol A, Omland T, Gerhard M, et al. Hyperhomocysteinemia is associated with impaired endothelium-dependent vasodilation in humans. Circulation 1997; 95: 119-21
54. Woo KS, Chook P, Lolin YI. Hyperhomocysteinemia is a risk factor for arterial endothelial dysfunction in humans. Circulation 1997; 96: 2542-4
55. Chambers JC, McGregor A, Jean-Marie J, et al. Acute hyperhomocysteinemia and endothelial dysfunction. Lancet 1998; 351: 36-7
56. Wall RT, Harlan JM, Harker LA, et al. Homocysteine-induced endothelial cell injury in vitro: a model for the study of vascular injury. Thromb Res 1980; 18: 113-21
57. DeGroot PG, Willems C, Boers GHJ, et al. Endothelial cell dysfunction in homocystinuria. Eur J Clin Invest 1983; 13: 405-10
58. Starkebaum G, Harlan JM. Endothelial injury due to copper-catalyzed hydrogen peroxide generation from homocysteine. J Clin Invest 1986; 77: 1370-6
59. Dudman NBP, Hicks C, Wang J, et al. Human arterial endothelial cell detachment in vitro: its promotion by homocysteine and cysteine. Atherosclerosis 1991; 91: 77-83
60. Berman RS, Martin W. Arterial endothelial barrier dysfunction: actions of homocysteine and the hypoxanthine-xanthine oxidase free radical generating system. Br J Pharmacol 1993; 108: 920-6
61. Jones BJ, Rose FA, Tudball N. Lipid peroxidation and homocysteine induced toxicity. Atherosclerosis 1994; 105: 165-70
62. 12/folate status [abstract]. Circulation 1996; 94 Suppl. 1: 461-2
63. Freedman JE, Frei B, Welch GN, et al. Glutathione peroxidase potentiates the inhibition of platelet function by S-nitrosothiols. J Clin Invest 1995; 96: 394-400
64. Upchurch GR, Welch GN, Fabian AJ, et al. Homocysteine decreases bioavailable nitric oxide by a mechanism involving glutathione peroxidase. J Biol Chem 1997; 272: 17012-7
65. Dudman NBP, Wilcken DEL. Increased plasma copper in patients with homocystinuria due to cystathionine beta synthase deficiency. Clin Chim Acta 1983; 127: 105-13
66. Munro JM, Cotran RS. The pathogenesis of atherosclerosis: atherogenesis and inflammation. Lab Invest 1988; 58: 249-61
67. Rodgers GN, Kane WH. Activation of endogenous factor V by a homocysteine-induced vascular endothelial cell activator. J Clin Invest 1986; 77: 1909-16
68. Hajjar KA. Homocysteine-induced modulation of tissue plasminogen activator binding to its endothelial cell membrane receptor. J Clin Invest 1993; 91: 2873-9
69. Hajjar KA, Mauri L, Jacovina AT, et al. Tissue plasminogen activator binding to the annexin II tail domain-direct modulation by homocysteine. J Biol Chem 1998; 273: 9987-93
70. Nishinaga M, Ozawa T, Shimada K. Homocysteine, a thrombogenic agent, suppresses anticoagulant heparan sulfate expression in cultured porcine aortic endothelial cells. J Clin Invest 1993; 92: 1381-6
71. Fryer RH, Wilson BD, Fitzgerald LA, et al. Homocysteine, a risk factor for premature vascular disease and thrombosis, induces tissue factor activity in endothelial cells. Arterioscler Thromb 1993; 13: 1327-33
72. Stamler JS, Osborne JA, Jaraki O, et al. Adverse vascular effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen. J Clin Invest 1993; 91: 308-18
73. Graeber JE, Slott JH, Ulane RE, et al. Effect of homocysteine and homocystine on platelet and vascular arachidonic acid metabolism. Pediatr Res 1982; 16: 490-3
74. Harker LA, Slichter SJ, Scott CR, et al. Homocysteinemia: vascular injury and arterial thrombosis. N Engl J Med 1974; 291: 537-43
75. Harker LA, Ross R, Slichter SJ, et al. Homocysteine-induced arteriosclerosis: the role of endothelial cell injury and platelet response in its genesis. J Clin Invest 1976; 58: 731-41
76. Harker LA, Harlan JM, Ross R. Effect of sulfinpyrazone on homocysteine-induced endothelial injury and arteriosclerosis in baboons. Circ Res 1983; 53: 731-9
77. Durand P, Lussier-Cacan S, Blache D. Acute methionine load-induced hyperhomocysteinemia enhances platelet aggregation thromboxane biosynthesis, and macrophage-derived tissue factor activity in rats. FASEB J 1997; 11: 1157-68
78. Durand P, Prost M, Blache D. Pro-thrombotic effects of a folic acid deficient diet in rat platelets and macrophages related to elevated homocysteine and decreased n-3 polyunsaturated fatty acids. Atherosclerosis 1996; 121: 231-43
79. Tsai JC, Perrella MA, Yoshizumi M, et al. Promotion of vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis. Proc Natl Acad Sci USA 1994; 91: 6369-73
80. Tsai JC, Wang H, Perella MA, et al. Induction of cyclin A gene expression by homocysteine in vascular smooth muscle cells. J Clin Invest 1996; 97: 146-53
81. Majors A, Ehrhart LA, Pezacka EH. Homocysteine as a risk factor for vascular disease-enhanced collagen production and accumulation by smooth muscle cells. Arterioscer Thromb Vasc Biol 1997; 17: 2074-81
82. Nishio E, Watanabe Y. Homocysteine as a modulator of platelet-derived growth factor action in vascular smooth muscle cells: a possible role for hydrogen peroxide. Br J Pharmacol 1997; 122: 269-74
83. Tang LL, Mamotte CDS, Van Bockxmeer FM, et al. The effect of homocysteine on DNA synthesis in cultured human vascular smooth muscle. Atherosclerosis 1998; 136: 169-73
84. Tyagi SC. Homocysteine redox receptor and regulation of extracellular matrix components in vascular cells. Am J Physiol 1998; 274: C396-405
85. Blom HJ, Boers GHJ, Elzen JPAM, et al. Difference between pre-menopausal women and young men in the transamination pathway of methionine catabolism and the protection against vascular disease. Eur J Clin Invest 1988; 18: 633-8
86. Wouters MG, Moorrees MT, van der Mooren MJ, et al. Plasma homocysteine and menopausal status. Eur J Clin Invest 1995; 25: 801-5
87. Hak AE, Polderman KH, Westendorp IC, et al. Increased plasma homocysteine after menopause. Atherosclerosis 2000; 149 (1): 163-8
88. Ridker PM, Manson JE, Buring JE, et al. Homocysteine and risk of cardiovascular disease among postmenopausal women. JAMA 1999; 281 (19): 1817-21
89. Mijatovic V, Kenemans P, Netelenbos JC, et al. Postmenopausal oral 17-beta-estradiol continuously combined with dydrogesterone reduces fasting serum homocysteine levels. Fertil Steril 1998; 69: 876-82
90. van der Mooren MJ, Demacker PNM, Blom HJ, et al. The effect of sequential three-monthly hormone replacement therapy on several cardiovascular risk estimators in postmenopausal women. Fertil Steril 1997; 67: 67-73
91. Evio S, Titinen A, Turpeinen U, et al. Failure of the combination of sequential oral and transdermal estradiol plus norethisterone acetate to affect plasma homocysteine levels. Fertil Steril 2000; 74 (6): 1080-3
92. Barnabei VM, Phillips TM, Hsia J. Plasma homocysteine in women taking hormone replacement: the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. J Womens Health Gend Based Med 1999; 8 (9): 1167-72
93. Mijatovic V, van der Mooren MJ, Stehouwer CD, et al. Postmenopausal hormone replacement, risk estimators for coronary artery disease and cardiovascular protection. Gynecol Endocrinol 1999; 13 (2): 130-44
94. Kardos A, Casadei B. Hormone replacement therapy and ischaemic heart disease among postmenopausal women. J Cardiovasc Risk 1999; 6 (2): 105-12
95. Finkelstein J. Methionine metabolism in mammals: effect of age, diet and hormones on three enzymes of the pathway in rat tissues. Arch Biochem Biophys 1972; 122: 583-90
96. Anker G, Lonning PE, Ueland PM, et al. Plasma levels of the atherogenic amino acid homocysteine in postmenopausal women with breast cancer treated with tamoxifen. Int J Cancer 1995; 60: 365-8
97. Mijatovic V, Netelenbos C, van der Mooren MJ, et al. Randomized, double-blind, placebo-controlled study of the effects of raloxifene and conjugated equine estrogen on plasma homocysteine levels in healthy postmenopausal women. Fertil Steril 1998; 70 (6): 1085-9
98. Walsh BW, Paul S, Wild RA, et al. The effects of hormone replacement therapy and raloxifene on C-reactive protein and homocysteine in healthy postmenopausal women: a randomized, controlled trial. J Clin Endocrinol Metab 2000; 85(1): 214-8
99. De Leo V, La Marca A, Morgante G, et al. Randomized control study of the effects of raloxifene on serum lipids and homocysteine in older women. Am J Obstet Gynecol 2001; 184: 350-3
100. Brattstrom L. Vitamins as homocysteine-lowering agents. J Nutr 1996; 126: 1276S-80S
101. Ubbink JB. The role of vitamins in the pathogenesis and treatment of hyperhomo-cysteinemia. J Inherit Metab Dis 1997; 20: 316-25
102. Brattstrom LE, Israelsson B, Jeppsson J-O, et al. Folic acid: an innocuous means to reduce plasma homocysteine. Scand J Clin Lab Invest 1988; 48: 215-21
103. Anonymous. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials: Homocysteine Lowering Trialists' Collaboration. BMJ 1998; 316: 894-8
104. Brouwer IA, van Dusseldorp M, Thomas CMG, et al. Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial. Am J Clin Nutr 1999; 69: 99-104
105. De Leo V, La Marca A, Morgante G, et al. Low-dose folic acid supplementation reduces plasma levels of the cardiovascular risk factor homocysteine in postmenopausal women. Am J Obstet Gynecol 2000; 183: 945-7
106. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women: Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998; 280: 605-13
107. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002; 288: 321-33