Gender Is the Main Predictor of Wearing‐Off and Dyskinesia in Levodopa‐Naïve Patients with Parkinson's Disease

Background: Evidence suggests that female gender represents a risk factor for the development of motor/nonmotor fluctuations and dyskinesia in Parkinson's disease (PD). So far, no prospective study has analyzed this aspect in relation to the introduction of levodopa treatment. Objective: This prospective multicenter study aims to assess the development of motor/nonmotor fluctuations and dyskinesia based on gender over a 2-year observation period in PD patients starting levodopa. Methods: Two hundred and eighty-nine PD patients requiring levodopa at baseline were enrolled at 17 Movement Disorders Centers and followed for 2 years. Gender differences in the development of fluctuations, defined as a score ≥2 in the 19-item Wearing-Off Questionnaire, and dyskinesia, defined by Movement Disorders Society Unified Parkinson's Disease Rating Scale Part IV (MDS-UPDRS-IV) score >0 on item 4.1 were assessed. Baseline predictors of such complications were evaluated by stepwise multivariate logistic regression analysis. Results: Two hundred and sixteen patients (139 men, 77 women) completed the follow-up (M24). By M24, 53,2% of men and 64.9% of women had fluctuations (P = 0.048), whereas 5% of men and 14.3% of women developed dyskinesia (P = 0.0185). Multivariate analysis showed that female gender significantly predicted wearing-off (Odds ratio [OR] = 1.930; P = 0.0333), whereas older age was a significant protective factor (for 5-year increase: OR = 0.712; P < 0.0001). Multivariate analysis showed that gender (OR = 3.405; P = 0.0228) and MDS-UPDRS Part III score (for a 5-unit increase: OR = 1.281; P = 0.0239) were significant predictors of dyskinesia at M24. Conclusions: Female gender was the strongest predictor of fluctuations and dyskinesia after 2-year intake of levodopa. This finding could have important implications for the development of gender-oriented therapeutic recommendations in early PD.