Metabolic Syndrome and Parkinson‘s Disease in Chinese Women: Menopausal Status as an Effect Modifier

Background Metabolic syndrome (MetS) has been implicated in neurodegenerative diseases, but its association with Parkinson‘s disease (PD) in women remains unclear, and the role of menopausal status as a potential effect modifier has not been examined. This study aimed to investigate: (1) whether MetS is associated with PD risk in Chinese women, and whether menopausal status modifies this relationship; (2) whether MetS is associated with disease severity in PD patients; and (3) whether estradiol mediates the MetS-PD association. Methods This cross-sectional study enrolled 213 Chinese women (103 PD patients, 110 healthy controls). MetS was defined using modified NCEP-ATP III criteria incorporating four components, with a continuous MetS score (0–4) calculated for dose-response analyses. Multivariable logistic regression assessed MetS-PD associations with hierarchical adjustment. Subgroup analyses were stratified by menopausal status with formal interaction testing. Sensitivity analysis stratified by disease duration was performed to evaluate reverse causality. Mediation analysis with 2,000 bootstrap resamples examined whether estradiol mediates the MetS-PD association. Within the PD subgroup (n = 103), linear regression examined associations between MetS and severity outcomes. Results PD patients had significantly lower BMI (22.9 vs. 24.6 kg/m², P < 0.001), higher HDL-C (1.4 vs. 1.2 mmol/L, P < 0.001), and lower MetS score (1.2 vs. 1.5, P = 0.020) than controls. The MetS score showed an inverse dose-response association with PD (adjusted OR per 1-point increase = 0.71, 95% CI: 0.52–0.95, P = 0.023), predominantly driven by women with menopause at or after age 45 (OR = 0.61, 95% CI: 0.44–0.84, P = 0.003; P for interaction = 0.097). Disease duration-stratified analysis showed the inverse association was strongest in early-stage PD (β=−0.37, P = 0.035; P for trend = 0.050), supporting disease-driven metabolic reversal. Estradiol did not mediate the MetS-PD association (indirect effect = − 0.0054, P = 0.300; 5.7% mediated). Among PD patients, MetS was not significantly associated with UPDRS-III, NMS, or MoCA (all P > 0.05). Conclusions MetS is paradoxically associated with lower PD risk in Chinese women, with menopausal status as a potential effect modifier, supporting the reverse causality hypothesis. Estradiol does not mediate this association, suggesting that the metabolic-neurodegenerative relationship operates largely through central pathways rather than peripheral sex hormone mechanisms. Once PD is established, MetS does not appear to influence disease severity. These findings highlight the importance of considering reproductive stage in future metabolic-neurodegeneration research.