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


METHODS
We enrolled 79 healthy postmenopausal women (mean [+/- SD] age, 56 +/- 4 years) and randomly assigned them to receive continuous estrogen/progestin therapy (n = 26; 17beta-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.


RESULTS
Treatment with genistein increased levels of nitrites/nitrates (mean increase, 21 micromol/L; 95% confidence interval [CI]: 15 to 26 micromol/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).


CONCLUSIONS
One year of genistein therapy improves endothelium function in postmenopausal women to a similar extent as does an estrogen/progestin regimen.
Squadrito
Francesco
F
Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, School of Medicine, University of Messina, Italy. Francesco.Squadrito@unime.it
Altavilla
Domenica
D
Crisafulli
Alessandra
A
Saitta
Antonino
A
Cucinotta
Domenico
D
Morabito
Nunziata
N
D'Anna
Rosario
R
Corrado
Francesco
F
Ruggeri
Pietro
P
Frisina
Nicola
N
Squadrito
Giovanni
G
D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000502:physiology; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D005260:Female; D019833:Genistein / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077563:Norethindrone Acetate; D017698:Postmenopause / Q000502:physiology*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
D015415:Biomarkers; D019332:Endothelin-1; D009566:Nitrates; D009573:Nitrites; D004958:Estradiol; D000077563:Norethindrone Acetate; D019833:Genistein; D009640:Norethindrone