Stress In Postmenopausal Women Research Articles

Effects of menopause and tibolone on antioxidants in postmenopausal women

Oxidative stress has been implicated in the pathogenesis of ageing and menopause, and can arise through the increased production of lipid peroxides and/or a deficiency of antioxidant defence. To investigate the effects of the menopause and tibolone treatment (2.5 mg/day for six months) on plasma antioxidants and lipid peroxidation. Plasma concentrations of ascorbic acid, alpha-tocopherol, total thiol groups, caeruloplasmin, erythrocyte glutathione (GSH) and malondialdehyde (MDA) were measured in 24 postmenopausal and 24 premenopausal healthy women. Data analysis indicates a significant decrease in plasma ascorbic acid, alpha-tocopherol, total thiol groups, [corrected]erythrocyte GSH and a significant increase in lipid peroxides (expressed as MDA concentrations) in postmenopausal women. There was no significant difference between control and study groups in the mean plasma caeruloplasmin concentrations. It was found that there is a significant increase in alpha-tocopherol and significant decrease in lipid peroxide concentrations in postmenopausal after tibolone treatment. The menopause is associated with an increase in oxidative stress and a decrease of some antioxidants, such as ascorbic acid, alpha-tocopherol, total thiols and erythrocyte GSH. Tibolone treatment leads to a decrease in concentrations of plasma lipid peroxide, probably by stimulating direct and indirect mechanisms of tocopherol regeneration and increasing plasma concentrations of vitamin E. However, due to the relatively small numbers involved this study can be regarded as a pilot. Further studies performed on a larger scale are necessary to establish the exact mechanisms of tibolone in inhibiting oxidative stress in postmenopausal women.

Behaviour of some indicators of oxidative stress in postmenopausal and fertile women

Objective Unsaturated fatty acids are known to have a crucial role in the pathogenesis of atherosclerosis. They are very sensitive to oxidation caused by excess free oxygen radicals and the consequent oxidative status, and it is well known that lipid and lipoprotein metabolism is markedly altered in postmenopausal women. Oxidative stress is involved in the pathophysiology of atherosclerosis and our study aim was to assess the presence of such stress in postmenopausal women. Design One hundred and one women were enrolled in the study. Fifty were fertile (32.5 ± 1.1 years) with regular menses and fifty-one were postmenopausal women (52.1 ± 1.3 years). None of the study cohort had ever used hormone replacement therapy. Malonaldehyde (MDA), 4-hydroxynenal (4-HNE), oxidized lipoproteins (ox LDL) and glutathione peroxidase (GSH-PX) values were determined as we believe they reveal oxidative stress. Results MDA, 4-HNE and ox LDL concentrations were higher in postmenopausal than fertile women ( p < 0.001), while GSH-PX concentrations were significantly higher in fertile women than in postmenopausal subjects ( p < 0.001). Conclusions Our data revealed the presence of oxidative stress in postmenopausal women.

Oxytocinergic activity is linked to lower blood pressure and vascular resistance during stress in postmenopausal women on estrogen replacement

Estrogen administration results in increased release of the oxytocin (OT) prohormone reflected by increases in oxytocin intermediate peptide (OT Int) in both animal models and humans, and sequential treatment of ovariectomized rats with estrogen/progesterone then progesterone withdrawal leads to increased hypothalamic OT mRNA. Blood pressure (BP) reductions have been related to increased exogenous and endogenous OT in rats and to higher endogenous OT activity in premenopausal women, but not previously in postmenopausal women. Thus, we used plasma obtained at rest and during a speech stressor from 54 postmenopausal women who participated in a 6-month randomized trial of oral conjugated estrogens vs. placebo to examine effects of estrogen replacement therapy (ERT) on plasma OT and OT Int levels and their relationships to changes in BP during the trial. ERT alone and with progesterone (but not placebo) led to significant increases in plasma levels of OT Int, but no change in plasma OT levels. Women showing greater increases in OT Int during treatment showed greater decreases in BP and total vascular resistance during a series of behavioral stressors compared to women with moderate or no increases in OT Int, even after controlling for effects related to treatment condition or to changes in plasma estradiol. The findings suggest that enhanced oxytocinergic activity may contribute to BP decreases associated with ERT in more responsive postmenopausal women.

Effect of short-term hormone therapy on oxidative stress and endothelial function in African American and Caucasian postmenopausal women

Objective In postmenopausal women (PMW), the effect of a short-term course of estrogen/progestin HT on free radical oxidative stress was evaluated. In addition, HT’s effect on plasma nitric oxide (NO) activity was determined as a measure of vascular endothelial function. We investigated the relationship of these markers and HT across race and the cardiovascular risk factors of smoking, diabetes and hypertension. Design A prospective, observational study comparing preintervention and postintervention. Setting Academic research center. Patient(s) Twenty-seven (14 African American and 13 Caucasian) PMW volunteers. Intervention(s) Six weeks of continuous, combined estrogen/progestin HT. Main outcome measure(s) Plasma concentrations of free 8-epi-prostaglandin F 2α (8-isoprostane) before and after HT were compared as a measure of oxidative stress. Nitrite, the stable oxidation metabolite of NO, was measured by the Greiss reaction after nitrate reduction to nitrite with cadmium. Results Plasma levels of free 8-isoprostane decreased significantly after 6 weeks of HT. Although almost all subjects benefited from the reduction in free 8-isoprostane, PMW with at least one cardiovascular risk factor (n = 19) demonstrated higher free 8-isoprostane than did subjects with no risk factors. Plasma levels of nitrite increased after 6 weeks of HT, but the difference was not statistically significant. Caucasian PMW demonstrated a greater increase in plasma levels of nitrite after 6 weeks of HT as compared with African American subjects, who exhibited almost no change. Conclusion(s) Short-term administration of HT significantly reduces oxidative stress in PMW and is consistent across race. However, there was an observed racial difference in endothelial NO response to HT between African American and Caucasian PMW.

The Effects of Estrogen and Raloxifene Treatment on Antioxidant Enzymes in Brain and Liver of Ovarectomized Female Rats

Recent studies documented that estrogen have antioxidant properties in‐vitro, there are conflicting results on the effect of estrogen in vivo. We aimed to investigate the effects of estradiol and Raloxifene on the antioxidant enzyme [superoxide dismutase (SOD) and catalase (CAT)] activities and MDA levels in brain and liver homogenates of ovariectomized female rats. Twelve weeks after ovariectomy, female Sprague–Dawley rats (n = 26) were divided into three groups: (1) Ovariectomized placebo group (n = 6) was given physiologic saline. (2) Estrogen group (n = 10) was given Ethynyl estradiol, 0.1 mg/kg sc. (3) Raloxifene group (n = 10) was given raloxifene, 1 mg/kg sc during 8 weeks. Ten rats were used as naive controls without any treatment (Sham operated group, n = 10). Ovariectomy lead to an increase in the CAT activities in liver tissue samples compared to the sham group ( p = 0.056, Mann–Whitney test). While estrogen treatment reversed to normal levels of CAT activities, raloxifene remained as ineffective. Superoxide dismutase activities and MDA levels in liver were remained unchanged in all groups. There was no significant change in the brain tissue SOD and CAT activities between the control, ovariectomy, estrogen treated, and raloxifen treated groups. We determined an increase in MDA levels in brain of ovariectomised rat ( p = 0.02). While raloxifene treatment reversed to normal levels of MDA ( p = 0.008), estrogen treatment failed. Our data showed that estrogen may play a role in regulation of CAT and SOD activities in liver due to its antioxidative effects. We can suggest that estrogen and raloxifene exert their antioxidative effects in brain rather than liver. Since Raloxifene's effect is more clear than estradiol, raloxifene may be suggested primarily for treatment and/or prevention of diseases which can be resulted from oxidative stress in postmenopausal women.

Blood pressure control and hormone replacement therapy in postmenopausal women at risk for coronary heart disease

Background Coronary heart disease (CHD) in women is strongly associated with estrogen deprivation. For example, risk for CHD increases dramatically after menopause. However, the role of hormone replacement therapy (HRT) in CHD prevention currently is unresolved. To better understand CHD in women, the precise mechanisms by which estrogen affects circulatory function require clarification. Evidence suggests that exogenous estrogen may affect blood pressure (BP) control, but its interaction with other CHD risk factors has not been systematically characterized. The present study examines the role of mildly elevated resting BP, family history of CHD, and HRT on BP responses to stress in postmenopausal women. Methods Postmenopausal women on long-term HRT were recruited along with a control group of postmenopausal women not on HRT. These women were divided into higher versus lower risk for CHD on the basis of resting BP and family history of CHD. BP control mechanisms were assessed before, during, and after a computer-controlled laboratory stressor. Results Results indicate that women with elevated resting BP and positive family history of CHD have exaggerated BP reactivity to stress and that HRT inhibits this effect. Conclusions This study suggests that unmedicated postmenopausal women with mildly elevated resting BP and positive family history of CHD have altered BP control as indicated by exaggerated BP responses to stress. HRT eliminates the cumulative effect of resting BP and family history on BP reactivity, suggesting that the circulatory effects of estrogen replacement may operate, at least in part, through normalization of BP reactivity in higher-risk postmenopausal women. (Am Heart J 2002;143:711-7.)

EFFECTS OF HORMONAL REPLACEMENT THERAPY ON OXIDATIVE STRESS AND TOTAL ANTIOXIDANT CAPACITY IN POSTMENOPAUSAL HEMODIALYSIS PATIENTS

Background: Oxidative stress is known to be implicated in the pathogenesis of atherosclerotic cardiovascular disease. Many studies have demonstrated that hormone replacement therapy (HRT) has beneficial effects on oxidation injury in postmenopausal women with normal renal function. In this study, we examined the effects of HRT on plasma malondialdehyde (MDA) level and total antioxidant capacity (TAC) in postmenopausal hemodialysis women. Methods: We randomly assigned 70 postmenopausal women on maintenance hemodialysis into either a HRT group or a control group. Oral conjugated estrogen (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) was given daily for 12 weeks in HRT group. Plasma MDA, TAC, albumin, uric acid and C-reactive protein (CRP) were measured before, 4 and 12 weeks after the start of medication in the HRT group. In the control group, the same parameters were measured without HRT. Results: There was no difference in baseline values between the two groups. In the control group (n = 32), all these parameters showed no change at 4 and 12 weeks. HRT decreased MDA from 1.32 (0.55–1.88) µM to 1.08 (0.44–1.50) µM (p<0.001) at 4 weeks and to 1.11 (0.50–1.37) µM (p<0.001) at 12 weeks (n = 33). TAC was not changed at 4 weeks, however, it decreased from 1.59 (1.27–2.00) mM to 1.45 (1.08–1.65) mM (p<0.05) at 12 weeks. The albumin, uric acid and CRP levels were not changed significantly after HRT. Conclusions: These results suggest that HRT has a favorable effect on oxidative stress in postmenopausal women with ESRD as in the general population.

Effect of low-dose estrogen on hemodynamic response to stress

Objective: To determine the effect of low-dose esterified estrogen on hemodynamic responses at rest and during stress in postmenopausal women, and to compare the changes with those seen with conjugated equine estrogen. Design: Open-label study of esterified estrogen compared with a double-blind, placebo-controlled investigation of conjugated equine estrogen. Setting: Healthy volunteers in an academic research environment. Patient(s): Postmenopausal women with normal endometrium, not currently using hormones. Intervention(s): Cardiovascular parameters at rest and in response to stressors were assessed in 11 postmenopausal women before and 6 months after receiving 0.3 mg esterified estrogen. Responses were compared with 42 postmenopausal women randomized to 0.625 mg conjugated equine estrogen or placebo. Main Outcome Measure(s): Changes in mean arterial pressure (MAP) and vascular resistance index from before to after treatment. Result(s): At rest, MAP increased 3.3 ± 1.5 mm Hg (±SD) in the placebo group, while declining 2.3 ± 1.5 mm Hg and 4.8 ± 1.4 mm Hg, respectively, in the esterified estrogen and conjugated equine estrogen groups after treatment. During mental stressors, MAP dropped significantly in both treatment groups. At rest and during mental stressors, vascular resistance index decreased with estrogen treatment. Conclusion(s): Low-dose esterified estrogen improved hemodynamic patterns similar to standard doses of conjugated equine estrogen in postmenopausal women.

Hormone Replacement Therapy for Oxidative Stress in Postmenopausal Women With Hot Flushes

Hormone Replacement Therapy for Oxidative Stress in Postmenopausal Women With Hot Flushes

Hormone replacement therapy for oxidative stress in postmenopausal women with hot flushes

Objective: To assess the association of hot flushes during postmenopause with oxidative stress and to determine whether hormone replacement therapy (HRT) affects the plasma redox status of postmenopausal women. Methods: We conducted a prospective clinical study of 49 postmenopausal women who have ( n = 29) or do not have ( n = 20) hot flushes. Twelve of the postmenopausal women with hot flushes and six without were treated with HRT (estradiol patches and medroxyprogesterone acetate) for 4 months. Plasma level of estradiol, total antioxidant status, reduced sulfhydryl groups, lipoperoxides, total cholesterol, and triglycerides were measured at 4-month intervals in both groups, before and after treatment. Results: Postmenopausal women who have hot flushes, had lower total basal antioxidant status in plasma (.9 ± .01 compared with 1.14 ± .01 mmol/L), lower concentration of reduced sulfhydryl groups (145 ± 4 compared with 200 ± 3 μmol/L), and higher concentration of lipoperoxides (2.88 ± .04 compared with 2.61 ± .04 μmol/L) than women without hot flushes. After HRT, total antioxidant status and reduced sulfhydryl groups increased, and lipoperoxides decreased similarly in both groups. Hormone replacement therapy decreased the frequency of hot flushes per day from 11.2 ± 0.8 to 1.4 ± 0.3. Conclusion: Hot flushes in postmenopausal women were associated with the oxidative process. Hormone replacement therapy decreases oxidative stress and the number of episodes of hot flushes. Because oxidative stress is associated with a high risk for cardiovascular diseases, HRT might protect women with hot flushes.