Effects of soy germ isoflavones and hormone therapy on nitric oxide derivatives, low-density lipoprotein oxidation, and vascular reactivity in hypercholesterolemic postmenopausal women.

OBJECTIVE: To evaluate the effects of soy germ isoflavones and hormone therapy on vascular reactivity, the formation of nitric oxide derivatives, and lipid peroxidation in hypercholesterolemic postmenopausal women. DESIGN: Women were treated with soy germ, 17beta-estradiol or 17beta-estradiol + noretisterone acetate for 3 months after taking placebo for 1 month. The plasma concentrations of nitrite + nitrate and S-nitrosothiols were evaluated by gaseous phase chemiluminescence; nitrotyrosine, electronegative low-density lipoprotein, and estradiol levels were determined by enzyme-linked immunosorbent assay; cholesterol oxides and isoflavones were determined by gas chromatography and high-performance liquid chromatography, respectively. Vascular reactivity was analyzed by high-resolution ultrasonography. RESULTS: Soy germ isoflavones and hormone therapy induced a decrease in nitrite + nitrate, electronegative low-density lipoprotein, and cholesterol oxides, as well as an increase in S-nitrosothiols. Soy germ isoflavones lowered electronegative low-density lipoprotein, and cholesterol oxides more efficiently than did hormone therapy. Only soy isoflavones inhibited nitrotyrosine formation. A significant improvement of vascular reactivity was only seen in women treated with 17beta-estradiol. CONCLUSIONS: The soy germ isoflavones and 17beta-estradiol, alone or associated with noretisterone acetate, in the doses and forms used here, have similar effects on the bioavailability of nitric oxide. Soy germ treatment inhibited lipid peroxidation more effectively than hormone therapy.

Progesterone abolishes estrogen and/or atorvastatin endothelium dependent vasodilatory effects.

UNLABELLED: This double blind randomized placebo controlled study assessed the effects of atorvastatin, estradiol and norethisterone, isolated and in combination, on the lipid profile and on vascular reactivity, in post-menopausal women with hypercholesterolemia and arterial hypertension. Ninety-four women aged 50-65 were selected. All have received dietary counseling (4 weeks), placebo (4 weeks), and drug therapy (12 weeks): 17-beta estradiol 2mg/day (E) (n=17); E + norethisterone acetate 1mg/day (P) (n=18); Atorvastatin 10mg/day (A) (n=20); E + A (n=21) and E + P + A (n=18). All treatment modalities have significantly reduced total cholesterol (TC) (E=8.8%, E + P=10.1%, A=27.9%, A + E=29.4% and E + P + A=35.7%) and LDL-cholesterol (LDL-c) levels (E + P + A=46.6%, E + A=45.9%, A=40.2%, E=20.3%, and E + P=12.1%). As concerns HDL-cholesterol (HDL-c), Groups E and E + A had increases of 15.5% and 13.1%, respectively. The addition of a progesterone compound reduced its concentration (Group E + P=-9.1%, and Group E + P + A=-9.5%). By random, approximately half of the patients in each group were designated to the endothelial function evaluation (brachial artery ultrasound). We observed that in Group A (n=10), in Group E (n=10) and with the association (Group E + A) (n=7), there was a significant increase in the flow-mediated vasodilatation as compared to basal measurements. The addition of a progestin has annulled these benefits. CONCLUSIONS: Atorvastatin has promoted more beneficial effects on TC and LDL-c, whereas estradiol was responsible for an increase in HDL-c. The addition of a progesterone derivative abolished these benefits. Atorvastatin, estradiol or both together improved endothelial function, an effect suppressed by the addition of norethisterone.