Effects of the combined hormonal replacement drug estradiol valerate/levonorgestrel on climacteric complaints, endometrium and lipid profile of peri- and postmenopausal women.

The effects of the combined hormone replacement (HRT) drug estradiol valerate/levonorgestrel (Klimonorm) on climacteric complaints, endometrial status and lipid profile was studied in 100 peri- and postmenopausal women aged between 41 and 57 years. The duration of therapy was 6 months. The following parameters were investigated: Kuppermann index, endometrial thickness, duration of bleeding, arterial blood pressure, body weight and serum lipids and lipoproteins (total cholesterol TC, LDL cholesterol, HDL cholesterol, and triglycerides [TG]). A separate analysis was made for 27 patients who had abnormal lipid status before treatment. Total cholesterol above 6.0 mmol/l and/or LDL of more than 3.5 mmol/l was considered abnormal and those patients were labeled as "high risk". The results showed a statistically significant reduction in the severity of climacteric symptoms (Kupperman index). A large decrease in the score was observed during the first 3 months of treatment (from 27.9 at the start to mean values of 9.3, p < 0.001). A further slight decrease of the score to 4.0 (p < 0.001) was seen after 6 months of treatment. Endometrial thickness did not change. At the start of the treatment the mean duration of bleeding was 5.1 +/- 0.3 days and at the end of the 6th month it was 3.8 +/- 0.2 days (p < 0.001) Klimonorm favorably affected the lipid profile. TC decreased significantly during the therapy: by 5.2% (p < 0.05) in all women and 7.1% (p < 0.05) in the high risk group. LDL cholesterol decreased slightly: by 4.3% (p < 0.05) in all women and was more pronounced in the high risk group (7.0%, p < 0.01). HDL cholesterol increased by 12.1% (p < 0.01) in all women and by 14.7% (p < 0.001) in the high risk group. TG were elevated slightly by 9.5% (p < 0.05) in all women and 3.9% (p > 0.05) in the high risk group. LDL/HDL ratio decreased from 2.7 to 2.3 in all women and from 3.0 to 2.4 (p < 0.05) in the high risk group. No significant changes in systolic and diastolic blood pressure were recorded. Body weight did not change significantly during the treatment period.

Reduced concentrations of soluble adhesion molecules after antioxidant supplementation in postmenopausal women with high cardiovascular risk profiles--a randomized double-blind study.

BACKGROUND: One of the suggested mechanisms of increased cardiovascular risk in postmenopause is a loss of the antioxidant effects of estrogens. It has been shown that classical cardiovascular risk factors increase oxidative stress on the arterial wall, and that endothelial cells react to this insult by increased expression of cellular adhesion molecules (CAM), which in turn are markers of arterial wall inflammation. METHODS: A randomized, placebo-controlled, double-blind study was performed in 60 postmenopausal women with high cardiovascular risk profiles, but free from clinical atherosclerotic disease. Patients were randomized to either antioxidant supplementation (using a combination of natural antioxidants; n = 30) or placebo (n = 30), and followed for 12 weeks. The concentrations of the adhesion molecules sVCAM-1 and sICAM-1 were measured by ELISA at baseline and at the end of the study, as well as total cholesterol, LDL, HDL, triglycerides and blood pressure. RESULTS: 27 women in the antioxidant supplementation group and 29 on placebo completed the study. At baseline, there were no significant differences in measured parameters between the groups: sICAM-1 concentrations were 341.8 +/- 116.9 vs. 349.9 +/- 104.6 ng/ml (active treatment vs. placebo; p = n.s.) and sVCAM-1 concentrations were 780.5 +/- 325.8 vs. 761.0 +/- 333.7 ng/ml (p = n.s.). In contrast, at the end of the study, sICAM-1 concentrations were 301.6 +/- 56.0 vs. 356.0 +/- 134.8 ng/ml (active treatment vs. placebo; p = 0.053) and sVCAM-1 concentrations were 656.0 +/- 326.5 vs. 818.5 +/- 381.0 ng/ml (p = 0.04). There were no significant differences between or changes within the groups in measured cholesterol and blood pressure. CONCLUSION: Antioxidant supplementation reduces serum concentrations of endothelium-derived adhesion molecules sICAM-1 and sVCAM-1 in postmenopausal women with high cardiovascular risk profiles.

Serum level of IgG autoantibodies against oxidized low density lipoproteins and lag-phase of serum oxidation in coronary heart disease--inverse correlation.

High affinity IgG autoantibodies (ABs) against oxLDLs and lag-phase of serum oxidation were tested in patients with coronary heart disease (CHD). Fifty one (37 M/14 F) patients with CHD defined as Q-wave myocardial infarction and/or stenosis of more than 50% and 51 (34 M/17 F) healthy blood donors as controls participated in this study. LDLs were isolated by gradient ultracentrifugation and oxidized with CuSO4. The modified LDLs (oxLDLs) or native LDLs (nLDLs) were used as antigens in an enzyme immunoassay (ELISA) to detect IgG ABs in both groups. The serum was oxidized by CuSO4 and the oxidation was monitored spectrophotometrically at lambda = 234 nm to follow the formation of conjugated diens. The lag-phase (in minutes) is the interval between the addition of CuSO4 to the serum and the beginning of extensive oxidation (increasing absorbance at 234 nm). The concentrations of total cholesterol, triglycerides, HDL-cholesterol, apo-A and apo-B were measured as well. The mean level of ABs against oxLDLs (expressed as optical density units) was 0.590 +/- 0.330 in CHD-patients vs 0.244 +/- 0.200 in controls (p < 0.001). The lag-phase in minutes was 47.00 +/- 27.19 in CHD-patients and 80.23 +/- 26.30 in controls (p < 0.001). A negative correlation between ABs levels and lag-phase was established in CHD-patients (r = -0.69, p < 0.001) and controls (r = -0.62, p < 0.001). A poor correlation was established between ABs levels or lag-phase, on one hand, and other measured parameters. In conclusion, the lag-phase of serum oxidation by Cu2+ could be informative for LDL susceptibility to modification and the extent of consequent humoral immune response.

Oxidation of low density lipoproteins leads to disturbance of their binding with alpha-tocopherol.

The dynamics of binding of exogenous alpha-tocopherol (alpha-T) added to native or oxidatively modified LDLs (LDLs or oxLDLs) were investigated. Venous blood from 31 clinically healthy blood donors (15 males and 16 females) was used. LDLs were isolated by density gradient ultracentrifugation. LDLs were oxidized in vitro by CuSO4. LDLs or oxLDLs were enriched with exogenous alpha-T (initial concentrations: 0; 10; 20; 50; or 100 nmol per mg protein). The contents of alpha-T in LDLs or in oxLDLs were measured by HPLC. Lag-phase of LDL oxidation before or after saturation with alpha-T was recorded. Correlation analysis of the lag-phase of LDL oxidation and alpha-T content in LDLs was carried out by the method of Esterbauer et al. The experimental results demonstrated that: (i) alpha-T was incorporated into native LDLs to a higher extent as compared to oxLDLs. (ii) A saturation of LDLs and oxLDLs with alpha-T was observed. (iii) A positive correlation was observed between the duration of the lag-phase of LDL oxidation in vitro and the content of alpha-T in LDLs. (iv) Based on LDL saturation with alpha-T, the persons could be classified in two groups: LDLs from group I of 26 persons were found to incorporate exogenous alpha-T to the extent of 1.8 to 3 times its initial concentration; LDLs from group II of 5 persons incorporated little or no exogenous alpha-T. In the first group, oxidation of LDLs lead to a considerable decrease in alpha-T dependent variable k and to a moderate reduction of alpha-T-independent variable alpha in the equation of Esterbauer et al.: lag-phase = k.[alpha-tocopherol]+alpha. In the second group, oxidation of LDLs lead to insignificant changes in k, as well as in a. (v) According to the levels of k and a the native LDLs from the second group of 5 persons were very close to oxLDLs from the first group of 26 persons. Presumably, native LDLs from the second group of persons were initially oxidatively modified, and probably this will be a risk group in relation to atherogenic disorders.

Oxidative modifications of blood serum in humans with coronary artery disease.

Oxidative modifications of blood serum in humans with and without coronary artery disease were investigated. Four parameters were analyzed: the intensity of serum fluorescence, which is indicative of the content of lipofuscine-like lipid peroxidation products; the content of thiobarbituric acid-reactive substances; the lag-phase of serum oxidation by azo-compounds; and the content of lipophilic natural antioxidants--alpha-tocopherol, beta-carotene and ubiquinol-9(10). It was found that coronary artery disease resulted in a significant increase of serum fluorescence and the content of TBARS. The atherogenic disorders in humans with coronary artery disease drastically decreased the lag-phase of serum oxidation in the presence of 2,2'-azo-bis-(2-amidinopropane) dihydrochloride. The oxidative modifications of serum were in close correlation with the balance of natural lipophilic antioxidants in blood serum, i.e. alpha-tocopherol, ubiquinols and beta-carotene. The contents of all antioxidants tested in serum were significantly decreased in patients with coronary artery disease.