Clinical study| Volume 114, ISSUE 6, P470-476, April 15, 2003

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Effect of genistein on endothelial function in postmenopausal women: a randomized, double-blind, controlled study



      Genistein, a phytoestrogen found in soybeans, corrects endothelial dysfunction induced by oophorectomy in animals. Using a double-blind, controlled, randomized design, we evaluated its effects on endothelial function in women.


      We enrolled 79 healthy postmenopausal women (mean [± SD] age, 56 ± 4 years) and randomly assigned them to receive continuous estrogen/progestin therapy (n = 26; 17β-estradiol [1 mg/d] combined with norethisterone acetate [0.5 mg/d]), genistein (n = 27; 54 mg/d), or placebo (n = 26). Brachial artery flow–mediated, endothelium-dependent vasodilation and plasma levels of nitrites/nitrates (a marker of nitric oxide metabolism) and endothelin-1 were measured at baseline and after 1 year of therapy.


      Treatment with genistein increased levels of nitrites/nitrates (mean increase, 21 μmol/L; 95% confidence interval [CI]: 15 to 26 μmol/L; P <0.001 vs. placebo); estrogen/progestin therapy caused similar changes (P <0.001 vs. placebo). Plasma endothelin-1 levels decreased following 12 months of genistein (mean decrease, 7 pg/mL; 95% CI: 3 to 10 pg/mL; P <0.001 vs. placebo) and after 12 months of estrogen/progestin (P <0.001 vs. placebo). When compared with placebo, brachial artery flow–mediated dilation was improved by genistein (mean increase, 5.5%; 95% CI: 3.9% to 7.0%; P <0.001) and by estrogen/progestin (P <0.001). There were no significant differences between estrogen and genistein for any of these parameters (all P >0.4).


      One year of genistein therapy improves endothelium function in postmenopausal women to a similar extent as does an estrogen/progestin regimen.


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        • Stampfer M.J.
        • Colditz G.A.
        Estrogen replacement therapy and coronary heart disease.
        Prev Med. 1991; 20: 47-63
        • Stampfer M.J.
        • Colditz G.A.
        • Willett W.C.
        • et al.
        Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the Nurses’ Health Study.
        N Engl J Med. 1991; 325: 756-762
        • Belchetz P.E.
        Hormonal treatment of postmenopausal women.
        N Engl J Med. 1994; 330: 1062-1071
        • Nelson H.D.
        • Humphrey L.L.
        • Nygren P.
        • Teutsch S.M.
        • Allan J.D.
        Postmenopausal hormone replacement therapy.
        JAMA. 2002; 288: 872-881
        • Writing Group for the Women’s Health Initiative Investigators
        Risks and benefits of estrogen plus progestin in healthy postmenopausal women.
        JAMA. 2002; 288: 321-333
        • 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: 605-613
        • Herrington D.M.
        • Reboussin D.M.
        • Brosnihan K.B.
        • et al.
        Effects of estrogen replacement on the progression of coronary-artery atherosclerosis.
        N Engl J Med. 2000; 343: 522-529
        • The Writing Group for the PEPI trial
        Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial.
        JAMA. 1995; 273: 199-208
        • Farhat M.Y.
        • Lavigne M.C.
        • Ramwell P.W.
        The vascular protective effects of estrogens.
        FASEB J. 1996; 10: 615-624
        • Reis S.E.
        • Gloth S.T.
        • Blumenthal R.S.
        • et al.
        Ethinyl estradiol acutely attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women.
        Circulation. 1994; 89: 52-60
        • Gilligan D.M.
        • Quyyumi A.A.
        • Cannon III, R.O.
        Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women.
        Circulation. 1994; 89: 2545-2551
        • Colditz G.A.
        • Hankinson S.E.
        • Hunter D.J.
        • et al.
        The use of estrogen and progestins and the risk of breast cancer in postmenopausal women.
        N Engl J Med. 1995; 332: 1589-1593
        • Clarkson T.B.
        Soy, soy phytoestrogens and cardiovascular disease.
        J Nutr. 2002; 132(suppl): 566S-569S
        • Glazier M.G.
        • Bowman M.A.
        A review of the evidence for the use of phytoestrogens as a replacement for traditional estrogen replacement therapy.
        Arch Intern Med. 2001; 161: 1161-1172
        • Mishra S.K.
        • Abbot S.E.
        • Choudhury Z.
        • et al.
        Endothelium-dependent relaxation of rat aorta and main pulmonary artery by phytoestrogens genistein and daidzein.
        Cardiovasc Res. 2000; 46: 539-546
        • Honore E.K.
        • Williams J.K.
        • Anthony M.S.
        • Clarkson T.B.
        Soy isoflavones enhance coronary vascular reactivity in atherosclerotic female macaques.
        Fertil Steril. 1997; 67: 148-154
        • Deodato B.
        • Altavilla D.
        • Squadrito G.
        • et al.
        Cardioprotection by the phytoestrogen genistein in experimental myocardial ischaemia.
        Br J Pharmacol. 1999; 128: 1683-1690
        • Squadrito F.
        • Altavilla D.
        • Squadrito G.
        • et al.
        Genistein supplementation and estrogen replacement therapy improve endothelial dysfunction induced by ovariectomy in rats.
        Cardiovasc Res. 2000; 45: 454-462
        • Supko J.G.
        • Phillips L.R.
        High-performance liquid chromatography assay for genistein in biological fluids.
        J Chromatogr B Biomed Sci Appl. 1995; 666: 157-167
        • Busse R.
        • Fleming I.
        Endothelial dysfunction in atherosclerosis.
        J Vasc Res. 1996; 33: 181-194
        • Walker H.A.
        • Dean T.S.
        • Sanders T.A.
        • Jackson G.
        • Ritter J.M.
        • Chowienczyk P.J.
        The phytoestrogen genistein produces acute nitric oxide-dependent dilation of human forearm vasculature with similar potency to 17β estradiol.
        Circulation. 2001; 103: 258-262
        • Minchenkoy A.
        • Caro J.
        Regulation of endothelin-1 gene expression in human microvascular endothelial cells by hypoxia and cobalt.
        Mol Cell Biochem. 2000; 208: 53-62
        • Guzic-Salobir B.
        • Keber I.
        • Seljeflot I.
        • Arnesen H.
        • Vrabic L.
        Combined hormone replacement therapy improves endothelial function in healthy postmenopausal women.
        J Intern Med. 2001; 250: 508-515
        • Vitale C.
        • Fini M.
        • Leonardo F.
        • et al.
        Effect of estradiol valerate alone or in association with cyproterone acetate upon vascular function of postmenopausal women at increased risk for cardiovascular disease.
        Maturitas. 2001; 40: 239-245
        • Teede H.J.
        • Liang Y.L.
        • Kotsopoulos D.
        • Zoungas S.
        • Cravent R.
        • McGrath B.P.
        A placebo-controlled trial of long-term oral combined continuous hormone replacement therapy in postmenopausal women.
        Clin Endocrinol (Oxf). 2001; 55: 673-682
        • Hodgson J.M.
        • Puddey I.B.
        • Beilin L.J.
        • Mori T.A.
        • Croft K.D.
        Supplementation with isoflavonoid phytoestrogens does not alter serum lipid concentration.
        J Nutr. 1998; 128: 728-732
        • Nestel P.J.
        • Yamashita T.
        • Sasahara T.
        • et al.
        Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women.
        Arterioscler Thromb Vasc Biol. 1997; 17: 3392-3398