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. 2025 May 29.
doi: 10.1002/mdc3.70143. Online ahead of print.

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

Maria Teresa Pellecchia  1 , Marina Picillo  1 , Maria Claudia Russillo  1 , Marianna Amboni  1 , Gennarina Arabia  2 , Laura Avanzino  3 , Margherita Canesi  4 , Alessia Catania  5 , Roberto Ceravolo  6 , Calogero Edoardo Cicero  7 , Roberto Cilia  8 , Isabel Colangelo  5 , Giovanna Dati  1 , Rosa De Micco  9 , Anna De Rosa  10 , Alessio Di Fonzo  11 , Roberto Eleopra  8 , Vincenza Fetoni  12 , Barbara Garavaglia  5 , Augusta Giglio  10 , Martina Giuntini  6 , Federica Invernizzi  5 , Giulia Lazzeri  13 , Roberta Marchese  14 , Alessandra Nicoletti  7 , Claudio Pacchetti  15 , Celeste Panteghini  5 , Manuela Pilleri  13 , Fabiana Radicati  16 , Chiara Reale  5 , Cesa Scaglione  17 , Andrea Soricelli  18 , Fabrizio Stocchi  19 , Alessandro Tessitore  9 , Laura Vacca  16 , Maria Antonietta Volontè  20 , Graziella Volpi  21 , Roberta Zangaglia  15 , Francesco Amato  22 , Carlo Ricciardi  22 , Michela Russo  22 , Paolo Barone  1   18
Affiliations

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

Maria Teresa Pellecchia et al. Mov Disord Clin Pract. .

Abstract

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.

Keywords: dyskinesia; gender; levodopa‐naïve; wearing‐off.

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