Abstract
BACKGROUND: Metabolic syndrome (MS) poses a growing threat to adolescent health, yet its sex-specific patterns remain inadequately characterized. This study aimed to investigate sex differences in MS prevalence, risk factor clustering, and metabolic phenotypes among U.S. adolescents. METHODS: We analyzed cross-sectional data from 6,989 adolescents aged 12-19 years, representing 30.97 million U.S. adolescents, from the National Health and Nutrition Examination Survey (1999-2020). MS was defined based on abdominal obesity, elevated blood pressure, hyperglycemia, and dyslipidemia, using weighted analyses to account for complex survey design. RESULTS: The overall MS prevalence was 5.1%, with a significantly higher prevalence in males than in females (6.1% vs. 4.1%, P = 0.017). Critically, no significant temporal trends in MS prevalence were observed over the 20-year period for either sex. Males accumulated more metabolic risk factors than females, showing higher rates of elevated BP (5.9% vs. 0.9%), fasting glucose (22.7% vs. 10.4%), and triglycerides (8.8% vs. 6.4%), whereas, females had higher prevalences of abdominal obesity (25.9% vs. 12.6%) and low HDL-C (22.8% vs. 18.8%). Moreover, metabolically unhealthy obesity was more common in males (13.7% vs. 10.0%). Subgroup analyses showed significant sex disparities persisted among ages 12-15, obese, non-Hispanic White, and high-income subgroups. Sensitivity analyses using alternative definitions, including waist-to-height ratio for abdominal obesity, robustly confirmed the male predominance in MS prevalence. CONCLUSION: Male U.S. adolescents exhibited a higher MS prevalence and a more unfavorable aggregation of metabolic risk factors than females. The stability of MS prevalence over the two-decade period highlighted the need for sex-specific and developmentally targeted interventions, especially within identified high-disparity subgroups.