Sex-specific differences in metabolic syndrome-related biomarkers across body fluids: a systematic review

Background Metabolic Syndrome (MetS) exhibits significant sex differences in clinical presentation and cardiometabolic outcomes. However, sex- and gender-specific patterns in biomarkers across different body fluids among patients with MetS have not been comprehensively synthesized so far. This systematic review aims to evaluate evidence on sex- and gender differences in conventional and emerging MetS biomarkers measured in human body fluids and to identify gaps relevant to sex-sensitive approaches for monitoring and treatment of MetS. Methods A PRISMA–guided systematic search of Medline, Embase, Cochrane, and Web of Science was conducted from inception to October 17, 2024. Eligible studies included adult participants with diagnosed MetS, enrolled both female and male participants or individuals with non-binary gender identities, and reported gender- or sex-stratified biomarker measurements in any body fluid with statistical comparison, in English-language peer-reviewed research. We performed a risk of bias assessment for the included studies. Findings were synthesized narratively by body fluid and biomarker class. Results Thirty-six studies (24 cross-sectional, 5 cohort, 1 case–control, 6 interventional) comprising 118,704 MetS participants (67,846 female; 50,858 male) were included. Most studies focused on whole blood or its derivatives such as serum and plasma. Only one study assessed saliva, and none evaluated urine, sweat, or interstitial fluid in a sex-stratified MetS context. None of the included studies reported data on gender-related dimensions, including identities. Across studies, male participants with MetS more consistently showed higher fasting blood glucose (FBG), triglycerides (TG), uric acid, and cardiovascular risk scores, reflecting a more insulin-resistant and atherogenic profile. Female participants more frequently demonstrated higher levels of high-density lipoprotein cholesterol (HDL-C), apolipoprotein-A (Apo-A), adiponectin, leptin, and antioxidant vitamins, suggesting relative preservation of hormonal and antioxidant profiles in women with MetS. Conclusion Sex-specific biomarker patterns in MetS are consistent across diverse populations but remain overwhelmingly derived from blood. Future studies should prioritize non-blood biofluids and explicitly account for gender-related determinants to enable sex- and gender-sensitive risk algorithms and patient-inclusive monitoring technologies.