ABSTRACT Association of oxidative stress and antioxidant parameters with metabolic risk markers in pre and post-menopausal women Background: Oxidative stress is a result of an imbalance between excess free radical and antioxidant defenses. The human body is naturally exposed to harmful free radicals (Reactive oxygen species (ROS) as a result of environmental stressors, dietary deficiencies and disease. Free radicals cause damages to human cells and tissues. Antioxidants are vital defense factors that neutralize these detrimental effects. Antioxidants contribute to decreasing oxidative stress by scavenging ROS or by donating electrons to free radicals, maintaining their stability. Managing free radical exposure and oxidative stress was shown to help in preventing metabolic disorders, ischemic heart disease, CVD, diabetes mellitus and many more. Several antioxidants have been linked to metabolic disorders these include thiols, Glutathione (GSH), glutathione peroxidase (GPx). On the other hand, there are factors that contribute to oxidative stress such as homocysteine (Hcy), and gamma glutamyltranferase (GGT). Hcy, in particular, has been found to contribute to increased cardiometabolic risk. Hcy and GGT becomes more prevalent in women as they age and reach menopause. During menopause, women have an increased CVD risk. Although antioxidants are linked to metabolic risk, studies on the association of antioxidants with anthropometric parameters, metabolic risk and hormones in women are limited. A major limitation is the effects of hormonal alterations during the menstrual cycle in women. Aim: The main aim of this study is to investigate the association between oxidative stress, antioxidant, metabolic risk parameters and female hormones and its relation in pre and post menopausal women in a setting of controlled hormone levels. Subjects and methods: This is a prospective cross-sectional study involving 410 apparently healthy Omani women (290 reproductive and 120 menopausal), age range (18-85 years). All subjects were free from metabolic disorders, take no medications, non-smokers, non-alcoholic, and are not pregnant. Anthropometric measures including height, weight, waist circumference, hip, fat percentage, visceral fat and skinfold thickness were recorded for all subjects. Blood samples were collected for all participants during the onset of the follicular phase to overcome the limitation of hormonal variation. In this study GSH, GPx, basal oxidation, thiols and other metabolic parameters were measured by specialized Kits and clinical biochemistry analyzers. All data obtained were analyzed by SPSS program (version 23). Result: Oxidative indices GSH, thiols, GGT and Hcy showed differences between pre and postmenopausal women while GPx had no significant difference (P >0.05). Favorable oxidative measures (GSH, Thiols) were high in reproductive women. On the other hand, the unfavorable oxidative measure (Hcy, GGT) were high in menopausal women. Hcy showed the greatest difference between pre and post-menopausal (P<0.001). Multiple regression analysis revealed that Hcy was the major positive predictor of basal oxidation (RP=0,023. P=0.036) followed by fat percent and visceral fat. Among all anthropometric measures, Hcy correlated with only visceral fat (P=0.002). Hcy also significantly correlated with decreased progesterone and estradiol levels, which support the findings of significant differences in Hcy levels between pre and postmenopausal. Conclusion: This study highlights the difference between antioxidant and oxidant oxidative markers in pre and postmenopausal women. It also emphasizes the importance of Hcy as a significant oxidative stress marker linked to visceral fat accumulation that may lead to CVD. Basal oxidation was mainly predicted by Hcy followed by fat percentage and visceral fat. These findings reveal the clinical importance of Hcy as an early marker of both oxidative stress and metabolic risk in women, and may contribute to better understanding and implementing early intervention measures.