Systemic Oxidative Stress Is Increased in Postmenopausal Women and Independently Associates with Homocysteine Levels

Oxidative stress plays a pivotal role in the pathogenesis of cardiovascular diseases (CVD). Postmenopausal women have an increased risk of developing CVD due to decreased estrogen availability, which is accompanied by increased oxidative stress. Serum free thiols (R-SH) provide a robust and powerful read-out of systemic oxidative stress. In this study, we aimed to establish serum levels of free thiols and explore associations between free thiols and demographic, clinical, and biochemical parameters related to obesity and the risk for developing CVD in both pre- and postmenopausal women. Serum free thiols were measured in a cohort consisting of healthy pre- (n = 223) and postmenopausal (n = 118) Omani women. Postmenopausal women had significantly lower levels of serum free thiols as compared to premenopausal women (762.9 ± 85.3 vs. 780 ± 80.9 μM, age-adjusted p < 0.001). Women′s age was positively associated with serum free thiol levels in premenopausal women (β = 0.36, p = 0.002), whereas an inverse association was observed in postmenopausal women (β = −0.29, p = 0.002). Homocysteine levels were significantly inversely associated with serum free thiol levels in both pre- (β = −0.19, p = 0.005) and postmenopausal (β = −0.20, p = 0.032) women, independent from known cardiovascular risk factors. In this study, we show that postmenopausal women are affected by increased systemic oxidative stress, which independently associates with homocysteine levels.

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Systemic Oxidative Stress, Aging and the Risk of Cardiovascular Events in the General Female Population

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.630543 ◽

2021 ◽

Vol 8 ◽

Author(s):

Martin F. Bourgonje ◽

Arno R. Bourgonje ◽

Amaal E. Abdulle ◽

Lyanne M. Kieneker ◽

Sacha la Bastide-van Gemert ◽

...

Keyword(s):

Oxidative Stress ◽

Cardiovascular Risk ◽

Postmenopausal Women ◽

Menopausal Status ◽

Female Population ◽

Serum Free ◽

Free Thiol ◽

Systemic Oxidative Stress ◽

Stage Disease ◽

End Stage

Introduction: Menopause is associated with increased cardiovascular risk, in which oxidative stress plays a pivotal role. Systemic oxidative stress is reflected by decreased levels of free thiols (R-SH, sulfhydryl groups), which are key components of the extracellular antioxidant machinery. In this study, we investigated the relation between serum free thiols as marker of oxidative stress and the female cardiovascular phenotype, as well as potential associations with the risk of cardiovascular (CV) events in pre- and postmenopausal women from the general population.Methods: Female participants (n = 2,980) of the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort study were included. Serum free thiol concentrations were analyzed for associations with demographic, clinical, biochemical, and gynecological parameters, as well as with menopausal status and, prospectively, with the risk of CV events.Results: Postmenopausal women had significantly reduced levels of serum free thiols (4.8 ± 1.0 vs. 5.2 ± 1.0 μmol/g, P < 0.001) compared to reproductive women. In multivariable analyses, serum free thiols were significantly associated with menopausal status (OR 0.70 [0.49–0.98], P = 0.039), even when adjusted for potential confounding factors, except for age (P = 0.550). Prospectively, serum free thiols were significantly associated with the risk of CV events (HR 0.52 [0.27–0.97], P = 0.040), even with covariate adjustment, although this disappeared when correcting for age.Conclusion: In this study, we revealed serum free thiols to be strongly associated with the female cardiovascular phenotype as well as with female risk of CV events, where the influence of age itself seemed to outweigh that of female menopause. Future studies are warranted to further unravel the clinical utility of serum free thiol levels in the context of female cardiovascular risk management.

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Mild Coronavirus Disease 2019 (COVID-19) Is Marked by Systemic Oxidative Stress: A Pilot Study

Antioxidants ◽

10.3390/antiox10122022 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2022

Author(s):

Larissa E. van Eijk ◽

Adriana Tami ◽

Jan-Luuk Hillebrands ◽

Wilfred F. A. den Dunnen ◽

Martin H. de Borst ◽

...

Keyword(s):

Oxidative Stress ◽

Treatment Options ◽

Critical Role ◽

Healthy Controls ◽

Serum Samples ◽

Discriminative Ability ◽

Discriminative Performance ◽

Serum Free ◽

Free Thiol ◽

Systemic Oxidative Stress

Oxidative stress has been implicated to play a critical role in the pathophysiology of coronavirus disease 2019 (COVID-19) and may therefore be considered as a relevant therapeutic target. Serum free thiols (R-SH, sulfhydryl groups) comprise a robust marker of systemic oxidative stress, since they are readily oxidized by reactive oxygen species (ROS). In this study, serum free thiol concentrations were measured in hospitalized and non-hospitalized patients with COVID-19 and healthy controls and their associations with relevant clinical parameters were examined. Serum free thiol concentrations were measured colorimetrically (Ellman’s method) in 29 non-hospitalized COVID-19 subjects and 30 age-, sex-, and body-mass index (BMI)-matched healthy controls and analyzed for associations with clinical and biochemical disease parameters. Additional free thiol measurements were performed on seven serum samples from COVID-19 subjects who required hospitalization to examine their correlation with disease severity. Non-hospitalized subjects with COVID-19 had significantly lower concentrations of serum free thiols compared to healthy controls (p = 0.014), indicating oxidative stress. Serum free thiols were positively associated with albumin (St. β = 0.710, p < 0.001) and inversely associated with CRP (St. β = −0.434, p = 0.027), and showed significant discriminative ability to differentiate subjects with COVID-19 from healthy controls (AUC = 0.69, p = 0.011), which was slightly higher than the discriminative performance of CRP concentrations regarding COVID-19 diagnosis (AUC = 0.66, p = 0.042). This study concludes that systemic oxidative stress is increased in patients with COVID-19 compared with healthy controls. This opens an avenue of treatment options since free thiols are amenable to therapeutic modulation.

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Serum Free Thiols Are Superior to Fecal Calprotectin in Reflecting Endoscopic Disease Activity in Inflammatory Bowel Disease

Antioxidants ◽

10.3390/antiox8090351 ◽

2019 ◽

Vol 8 (9) ◽

pp. 351 ◽

Cited By ~ 3

Author(s):

Arno R. Bourgonje ◽

Ruben Y. Gabriëls ◽

Martin H. de Borst ◽

Marian L. C. Bulthuis ◽

Klaas Nico Faber ◽

...

Keyword(s):

Oxidative Stress ◽

Disease Activity ◽

Severe Disease ◽

Fecal Calprotectin ◽

Redox Status ◽

Healthy Controls ◽

Serum Free ◽

Free Thiol ◽

Systemic Oxidative Stress ◽

Inflammatory Bowel

Oxidative stress plays a pivotal role in the pathogenesis of inflammatory bowel diseases (IBD). Serum free thiols (R-SH) reliably reflect systemic oxidative stress, since they are readily oxidized by reactive species. Here, we aimed to establish concentrations of serum free thiols in IBD and assessed their discriminating capacity regarding endoscopic disease activity. Albumin-adjusted serum free thiol concentrations were measured in 78 IBD patients (31 Crohn’s disease (CD) and 47 ulcerative colitis (UC) patients) and 50 healthy controls and analyzed for associations with disease parameters and their discriminative value regarding endoscopic disease activity (n = 54) or fecal calprotectin (n = 36) in patients for which those data were available. Mean serum free thiol concentrations were significantly lower in both CD and UC as compared to healthy controls (19.4 ± 3.1 and 17.8 ± 3.4 vs. 21.1 ± 1.9 µmol/g albumin, P < 0.001). Free thiols highly accurately discriminated between mild and moderate-to-severe disease activity, better than fecal calprotectin (FC) levels (AUC = 0.87, P < 0.001 vs. AUC = 0.76, P < 0.05, respectively) and this was maintained after cross-validation (AUC = 0.89, P < 0.001). Serum free thiols are reduced in IBD as compared to healthy controls and strongly correlate with the degree of endoscopic disease activity. Quantifying systemic redox status in IBD may be a promising, minimally invasive strategy to monitor IBD disease activity.

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Lifetime alcohol consumption and breast cancer: a case–control study in Finland

Public Health Nutrition ◽

10.1017/s1368980000000033 ◽

2000 ◽

Vol 3 (1) ◽

pp. 11-18 ◽

Cited By ~ 12

Author(s):

Satu Männistö ◽

Mikko Virtanen ◽

Vesa Kataja ◽

Matti Uusitupa ◽

Pirjo Pietinen

Keyword(s):

Breast Cancer ◽

Alcohol Consumption ◽

Postmenopausal Women ◽

Case Control Study ◽

Premenopausal Women ◽

Case Control ◽

Total Lifetime ◽

Increased Risk ◽

Control Study ◽

Current Alcohol

AbstractObjectiveTo study the association between lifetime alcohol consumption and the risk of breast cancer.Design and settingA case–control study carried out in eastern Finland. Information about alcohol consumption was obtained by two methods: a self-administered food frequency questionnaire (FFQ) including alcohol consumption during the previous 12 months, and a lifetime alcohol consumption questionnaire (AQ) which was administered by the study nurse.SubjectsThe study consisted of 301 breast cancer cases (25–75 years old) and 443 population controls.ResultsThe subjects reported higher current alcohol consumption in the AQ compared to the FFQ. According to the AQ, premenopausal cases consumed on average 28 g and controls 24 g alcohol week−1; in postmenopausal women the values were 15 and 14 g, respectively. About 30% of premenopausal and 60% of postmenopausal women were classified as non-drinkers. The correlation for current alcohol consumption between the FFQ and the AQ was 0.80 in premenopausal women but only 0.40 in postmenopausal women. Current alcohol consumption seemed to influence the reporting of total lifetime alcohol consumption. Current alcohol consumption was not associated with the risk of breast cancer either in premenopausal or postmenopausal women; neither were associations found between alcohol consumption at age of first use, use before the age of 30, or total lifetime alcohol consumption and the risk of breast cancer.ConclusionsOn average, one to three drinks per week did not increase the risk of breast cancer in this study. Consumption levels were, however, too low to exclude increased risk with high regular consumption. Further research is necessary on lifetime alcohol consumption.

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Anti-Mullerian hormone concentrations are inversely associated with subclinical atherosclerosis in premenopausal women

European Heart Journal ◽

10.1093/ehjci/ehaa946.3183 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

D Delialis ◽

I Lamprinoudaki ◽

S Stergiotis ◽

R Patras ◽

P Chatzivasileiou ◽

...

Keyword(s):

Risk Factors ◽

Lipid Profile ◽

Subclinical Atherosclerosis ◽

Acute Infection ◽

Premenopausal Women ◽

Reproductive Age ◽

Premature Menopause ◽

Inverse Association ◽

Increased Risk ◽

Cv Disease

Abstract Background Anti-Müllerian hormone (AMH) constitutes a marker of ovarian reserve and appears to have a predictive role regarding the time of menopause. Moreover, AMH is associated with adverse cardiac events. History of premature menopause and early onset of menopause have been associated with increased risk of cardiovascular (CV) disease. In addition, menopausal transition and duration of menopause have been associated with increased burden of subclinical atherosclerosis. However, the association between AMH as a marker of female reproductive age with atherosclerosis in premenopausal women is currently unknown. Purpose To investigate whether AMH concentrations are associated with markers of early atherosclerosis in healthy, normally menstruating women. Methods In a cross-sectional study, vascular structure and function were assessed by measurement of carotid and femoral intima-media thickness (IMT), lipid profile and serum AMH concentrations were assessed. Exclusion criteria were clinically overt CV disease, abnormal ovulatory cycles, polycystic ovarian syndrome, acute infection or chronic inflammatory disease, risk factors for CV disease and any medication Results Seventy premenopausal women, aged 32.7±6.5 years, were included. Mean AMH levels were lower in smokers than in non-smokers and negatively associated with total cholesterol (TC) levels. An inverse association between mean AMH concentrations and IMT in all segments was observed. No correlation with other markers of subclinical atherosclerosis or traditional CV risk factors was found. After multi-variable adjustment for traditional CV risk factors, the association between AMH concentrations combined IMT and carotid bulb IMT, remained significant. Conclusions In healthy, normally ovulating women, low AMH concentrations are associated with an adverse lipid profile and subclinical atherosclerosis, independently of traditional CV risk factors. This finding suggest a role of decreased follicular reserve with atherosclerotic disease. Funding Acknowledgement Type of funding source: None

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COMPONENTS OF A HEALTHFUL DIET ARE ASSOCIATED WITH WAIST CIRCUMFERENCE AMONG PRE- AND POSTMENOPAUSAL WOMEN

Innovation in Aging ◽

10.1093/geroni/igz038.214 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S55-S55

Author(s):

Lisa M Troy ◽

Sarah Witkowski

Keyword(s):

Waist Circumference ◽

Postmenopausal Women ◽

Premenopausal Women ◽

Visceral Adiposity ◽

Omega 3 ◽

Refined Grains ◽

Increased Risk ◽

Menopausal Women ◽

Post Menopausal ◽

Dark Green

Abstract After menopause, women are at increased risk of diabetes and cardiovascular disease. A contributing factor to increased risk may be weight gain, especially visceral adiposity. Diet plays a role in maintaining weight at all ages but less is known about the specific contributions of a healthful dietary pattern after menopause. Therefore, we evaluated associations between diet and WC as a measure of visceral adiposity. We compared 869 pre- (aged 35-45 years) and 353 post-menopausal (aged 40-65 years) women from NHANES III (1988-94). Women were pre-menopausal if they self-reported menses in the past 2 months and postmenopausal if they reported no menses in past 12 months and were aged > 40 years. Compared to premenopausal women, postmenopausal women consumed fewer Calories (-200 kcal/d) and had a higher mean waist circumference (+4.43 cm, p=0.007), after adjusting for age, race-ethnicity, height, physical activity, and smoking. Higher intakes of dark green vegetables (p=0.03) and lower intakes of potatoes (p=0.03), refined grains (p=0.001), and meats (p=0.04) were associated with lower WC for all women. Higher intakes of nuts and seeds and fish high in Omega-3 fatty acids were associated with smaller WC while higher intakes of poultry and dairy products were associated with higher WC in post- but not pre-menopausal women. Our findings generally support a diet high in nuts and seeds, dark green vegetables, and fish, and low in potatoes, refined grains, and meats. After menopause it may be important to incorporate fatty fish, nuts and seeds into the diet for lower visceral adiposity.

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Evaluation of Salivary and Serum Total Antioxidant Capacity and Lipid Peroxidation in Postmenopausal Women

International Journal of Dentistry ◽

10.1155/2020/8860467 ◽

2020 ◽

Vol 2020 ◽

pp. 1-5

Author(s):

Fatemeh Zovari ◽

Hadi Parsian ◽

Ali Bijani ◽

Ameneh Moslemnezhad ◽

Atena Shirzad

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Antioxidant Capacity ◽

Postmenopausal Women ◽

Total Antioxidant Capacity ◽

Premenopausal Women ◽

Control Group ◽

Antioxidant Power ◽

Whole Saliva ◽

Total Antioxidant

Objective. In menopause, reduction of estrogen hormone affects oxidative stress process in serum. Oxidative stress in saliva plays a significant role in the pathogenesis of oral diseases. The aim of this study was to investigate the total antioxidant capacity and lipid peroxidation in the serum and saliva of premenopausal and postmenopausal women. Methods. In this case control study, 50 postmenopausal women (case group) and 48 premenopausal women (control group) were selected. The unstimulated whole saliva and serum of the postmenopausal and premenopausal women were collected. The total antioxidant capacity (TAC) of the saliva and serum was measured by ferric reducing antioxidant power (FRAP). Also, malondialdehyde (MDA) was measured by thiobarbituric acid reactive substance (TBARS) method for serum and saliva. Then, the obtained data were analyzed by SPSS 17, whereby Mann–Whitney test and Spearman’s correlation test were used. P < 0.05 was considered statistically significant. Results. The postmenopausal group had significantly lower mean serum TAC and higher mean serum MDA than the control group ( P < 0 < 001 and P < 0.01 , respectively). The mean salivary TAC and MDA, however, did not differ significantly between the case and control group ( P = 0.64 and P = 0.08 , respectively). Conclusion. In postmenopausal women, with elevation of serum MDA and reduction of serum TAC, the extent of serum oxidative stress grows, but MDA and TAC levels of saliva do not change.

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The Association Between Phytosterol Intake and Breast Cancer Incidence in the Adventist Health Study-2 Cohort

Current Developments in Nutrition ◽

10.1093/cdn/nzaa044_051 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 352-352

Author(s):

Rawiwan Sirirat ◽

Yessenia Tantamango-Bartley ◽

Celine Heskey ◽

Ella Haddad ◽

Gary Fraser ◽

...

Keyword(s):

Breast Cancer ◽

Postmenopausal Women ◽

Cancer Incidence ◽

Breast Cancer Incidence ◽

Premenopausal Women ◽

Epidemiological Studies ◽

Health Study ◽

Breast Cancer Cell Lines ◽

Inverse Association ◽

Adventist Health Study

Abstract Objectives Breast cancer is the most diagnosed form of cancer among American women. Worldwide, it is second only to lung cancer. Phytosterols are phytochemicals found in plant foods that have potential benefits for breast cancer. Research on phytosterols and cancer associations to date has been limited to breast cancer cell lines and animal studies, and the results have been promising. Our objective is to examine the association between breast cancer incidence and phytosterol intake in the Adventist Health Study-2, a large cohort in North America. Methods The present study estimated the association between phytosterol intake and breast cancer incidence in 52,734 females who were part of the Adventist Health Study 2 (AHS-2) cohort. Breast cancer cases (n = 1050) were ascertained with tumor registries from 2008 to 2014. Phytosterols content in foods was quantified by using USDA 17 and other published sources. These values were used to estimate phytosterol intake from food intake assessed by a self-administered food frequency questionnaires (FFQ). Results Hazard ratios were below the null, but statistically non-significant for β-sitosterol [HR = 0.77, 95%CI (0.44–1.36)], campesterol [HR = 0.84, 95%CI (0.46–1.55)], stigmasterol [HR = 0.76 (0.46–1.26)], and total phytosterol [HR = 0.77, 95%CI (0.43–1.40)]. In premenopausal women, HRs ranged between 0.95–1.72; in postmenopausal women, HRs were below the null, ranging between 0.67–0.83. In both premenopausal and postmenopausal women, HRs were statistically non-significant. Conclusions The inverse association between phytosterol consumption and breast cancer incidence appears uncertain. The uncertainty possibly could be due to lack of power or measurement error. Additional epidemiological studies with a larger number of breast cancer cases, improved phytosterol intake estimates, or both are needed. Funding Sources Unilever Research &Development, Vlaardingen, The Netherlands.

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Effect of Menopause on Low Density Lipoprotein

Ibrahim Cardiac Medical Journal ◽

10.3329/icmj.v4i2.52989 ◽

2016 ◽

Vol 4 (2) ◽

pp. 32-36

Author(s):

Shafeya Khanam ◽

Nahid Reaz ◽

Shahnaj Akter Jahan ◽

Mirza Md Asaduzzaman ◽

Ayesha Siddika Purabi ◽

...

Keyword(s):

Postmenopausal Women ◽

Ldl Cholesterol ◽

Elevated Serum ◽

Premenopausal Women ◽

Outcome Variable ◽

Control Group ◽

Case Group ◽

Natural Menopause ◽

Increased Risk ◽

Significant Difference

Background and Objectives: The present study was done on postmenopausal and premenopausal women with an objective to evaluate the effect of menopause on LDL cholesterol. Patients & Methods: The cross-sectional analytical study was done in the Departments of Obstetrics & Gynaecology, Dhaka Medical College Hospital, Dhaka over a period 1 year between July 2012 to June 2013. A total of 60 women who underwent natural menopause were consecutively included in the study as case, while an equal number of premenopausal women were included as control. The outcome variable was level of serum LDL cholesterol. Result: The study demonstrated that 60% of postmenopausal women were > 50years old with mean age being 51.2 ± 2.7 years, whereas 40% of premenopausal women were in their 4th decades life with mean age being 39.1 ± 8.1 years (p = 0.001). There was no significant difference between the groups in terms of BMI with mean BMI of the former and the later groups being 24.45 ± 3.43 and 23.76 ± 3.46 kg/m2. The mean serum cholesterol was observed to be significantly higher in case group than that in the control group (212.3 ± 50.1 vs. 186.3 ± 38.2 mg/dl, p = 0.002). The LDL cholesterol was also significantly higher in the case group than that in the control group (141.47 ± 47.9 vs. 124.2 ± 31.5 mg/dl, p < 0.001). However, the groups were almost homogeneous with respect to HDL cholesterol and triglycerides (38.2 ± 5.0 vs. 37.6 ± 5.3 mg/dl, p =0.526 and 167.0 ± 67.2 vs. 181.0 ± 82.6 3 mg/dl, p = 0.311 respectively). Nearly three-quarters (73.3%) of the cases exhibited elevated serum LDL cholesterol compared to one-third (33.3%) of the controls. The risk of having raised LDL in case is more than 5(95% CI = 2.5 – 12.1) times higher than that in controls. The correlation graph between duration of menopause and serum LDL level showed that the two variables bear linear relationship (r = +0.338, p = 0.008). Conclusion: The postmenopausal women are at increased risk of having higher LDL cholesterol than the premenopausal women and longer the duration of menopause the higher the level of LDL Cholesterol. Ibrahim Cardiac Med J 2014; 4(2): 32-36

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Tocotrienol Supplementation Led to Higher Serum Levels of Lysophospholipids but Lower Acylcarnitines in Postmenopausal Women: A Randomized Double-Blinded Placebo-Controlled Clinical Trial

Frontiers in Nutrition ◽

10.3389/fnut.2021.766711 ◽

2021 ◽

Vol 8 ◽

Author(s):

Chwan-Li Shen ◽

Huanbiao Mo ◽

Dale M. Dunn ◽

Bruce A. Watkins

Keyword(s):

Oxidative Stress ◽

Postmenopausal Women ◽

Serum Levels ◽

Phospholipid Metabolism ◽

The Body ◽

Controlled Clinical Trial ◽

Serum Samples ◽

Major Health Problem ◽

Double Blinded ◽

And Oxidative Stress

Osteoporosis is a major health problem in postmenopausal women. Herein we evaluated the effects of 12-week tocotrienols (TT) supplementation on serum metabolites in postmenopausal, osteopenic women. Eighty-nine participants (59.7 ± 6.8 yr, BMI 28.7 ± 5.7 kg/m2) were assigned to 3 treatments: placebo (860 mg olive oil/day), 300mg TT (300 mg TT/day), and 600mg TT (600 mg TT/day) for 12 weeks. TT consisted of 90% δ-TT and 10% γ-TT. In this metabolomic study, we evaluated the placebo and 600mgTT at baseline and 12 weeks. As expected, TT and its metabolite levels were higher in the supplemented group after 12 weeks. At baseline, there were no differences in demographic parameters or comprehensive metabolic panels (CMP). Metabolomics analysis of serum samples revealed that 48 biochemicals were higher and 65 were lower in the 600mg TT group at 12 weeks, compared to baseline. The results confirmed higher serum levels of tocotrienols and lysophospholipids, but lower acylcarnitines and catabolites of tryptophan and steroids in subjects given 600mg TT. In summary, 12-week TT supplementation altered many serum metabolite levels in postmenopausal women. The present study supports our previous findings that TT supplementation helps reduce bone loss in postmenopausal osteopenic women by suppressing inflammation and oxidative stress. Furthermore, the body incorporates TT which restructures biomembranes and modifies phospholipid metabolism, a response potentially linked to reduced inflammation and oxidative stress.

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