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• Metabolic syndrome is a major risk factor for cardiovascular diseases. • Sex, and gendered related variables are important consideration for development of MetS. • older age, educational attainment less than university, and low income were associated with an increased risk of developing MetS. • significant interaction between sex and strata of age, education, income, smoking, and employment were identified showing that the reduced risk of MetS in female individuals was attenuated in the lowest education, income, and advanced age strata. • Gender-related factors such as income level and educational attainment play a greater role in the development of MetS in female than individuals. The burden of metabolic syndrome (MetS) and its components has been increasing mainly amongst male individuals. Nevertheless, clinical outcomes related to MetS (i.e., cardiovascular diseases), are worse among female individuals. Whether these sex differences in the components and sequalae of MetS are influenced by gender (i.e., psycho-socio-cultural factors)) is a matter of debate. Therefore, the purpose of this study was to determine the association between gender-related factors and the development of MetS, and to assess if the magnitude of the associations vary by sex. Data from the Colaus/PsyColaus study, a prospective population-based cohort of 6,734 middle-aged participants in Lausanne (Switzerland) (2003–2006) were used. The primary endpoint was the development of MetS as defined by the Adult Treatment Panel III of the National Cholesterol Education Program. Multivariable models were estimated using logistic regression to assess the association between gender-related factors and the development of MetS. Two-way interactions between sex, age and gender-related factors were also tested. Among 5,195 participants without MetS (mean age=51.3 ± 10.6, 56.1 % females), 27.9 % developed MetS during a mean follow-up of 10.9 years. Female sex (OR:0.48, 95 %CI:0.41–0.55) was associated with decreased risk of developing MetS. Conversely, older age, educational attainment less than university, and low income were associated with an increased risk of developing MetS. Statistically significant interaction between sex and strata of age, education, income, smoking, and employment were identified showing that the reduced risk of MetS in female individuals was attenuated in the lowest education, income, and advanced age strata. However, females who smoke and reported being employed demonstrated a decreased risk of MetS compared to males. Conversely smoking and unemployment were significant risk factors for MetS development among male adults. Gender-related factors such as income level and educational attainment play a greater role in the development of MetS in female than individuals. These factors represent novel modifiable targets for implementation of sex- and gender-specific strategies to achieve health equity for all people. [ABSTRACT FROM AUTHOR]