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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- Estrogen replacement therapy and coronary heart disease.Prev Med. 1991; 20: 47-63
- Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the Nurses’ Health Study.N Engl J Med. 1991; 325: 756-762
- Hormonal treatment of postmenopausal women.N Engl J Med. 1994; 330: 1062-1071
- Postmenopausal hormone replacement therapy.JAMA. 2002; 288: 872-881
- Risks and benefits of estrogen plus progestin in healthy postmenopausal women.JAMA. 2002; 288: 321-333
- 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
- Effects of estrogen replacement on the progression of coronary-artery atherosclerosis.N Engl J Med. 2000; 343: 522-529
- 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
- The vascular protective effects of estrogens.FASEB J. 1996; 10: 615-624
- Ethinyl estradiol acutely attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women.Circulation. 1994; 89: 52-60
- Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women.Circulation. 1994; 89: 2545-2551
- The use of estrogen and progestins and the risk of breast cancer in postmenopausal women.N Engl J Med. 1995; 332: 1589-1593
- Soy, soy phytoestrogens and cardiovascular disease.J Nutr. 2002; 132(suppl): 566S-569S
- 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
- Endothelium-dependent relaxation of rat aorta and main pulmonary artery by phytoestrogens genistein and daidzein.Cardiovasc Res. 2000; 46: 539-546
- Soy isoflavones enhance coronary vascular reactivity in atherosclerotic female macaques.Fertil Steril. 1997; 67: 148-154
- Cardioprotection by the phytoestrogen genistein in experimental myocardial ischaemia.Br J Pharmacol. 1999; 128: 1683-1690
- Genistein supplementation and estrogen replacement therapy improve endothelial dysfunction induced by ovariectomy in rats.Cardiovasc Res. 2000; 45: 454-462
- High-performance liquid chromatography assay for genistein in biological fluids.J Chromatogr B Biomed Sci Appl. 1995; 666: 157-167
- Endothelial dysfunction in atherosclerosis.J Vasc Res. 1996; 33: 181-194
- The phytoestrogen genistein produces acute nitric oxide-dependent dilation of human forearm vasculature with similar potency to 17β estradiol.Circulation. 2001; 103: 258-262
- Regulation of endothelin-1 gene expression in human microvascular endothelial cells by hypoxia and cobalt.Mol Cell Biochem. 2000; 208: 53-62
- Combined hormone replacement therapy improves endothelial function in healthy postmenopausal women.J Intern Med. 2001; 250: 508-515
- 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
- A placebo-controlled trial of long-term oral combined continuous hormone replacement therapy in postmenopausal women.Clin Endocrinol (Oxf). 2001; 55: 673-682
- Supplementation with isoflavonoid phytoestrogens does not alter serum lipid concentration.J Nutr. 1998; 128: 728-732
- Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women.Arterioscler Thromb Vasc Biol. 1997; 17: 3392-3398
Accepted: November 27, 2002
Received in revised form: November 19, 2002
Received: September 17, 2002
© 2003 Excerpta Medica Inc. Published by Elsevier Inc. All rights reserved.