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Observational Study
. 2025 Nov;12(11):1774-1783.
doi: 10.1002/mdc3.70143. Epub 2025 May 29.

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
Observational Study

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. 2025 Nov.

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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Conflict of interest statement

Ethical Compliance Statement: The study was approved by Comitato Etico Campania Sud (P.U. n. 4 obtained on February 4, 2019). Written informed consent was obtained for each enrolled patient. We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflict of Interest: This study was funded by AIFA, Italian Medicines Agency (grant: AIFA‐2016‐02364714).

The authors declare that they have no conflict of interest relevant to this work.

Financial Disclosures for the Previous 12 Months: The authors declare that there are no additional disclosures to report.

Figures

Fig. 1
Fig. 1
Study flowchart.
Fig. 2
Fig. 2
Percentage of patients developing wearing‐off (A) and motor fluctuations (B) based on gender assessed over a 2‐year observational period since the start of levodopa treatment.
Fig. 3
Fig. 3
Percentage of patients developing dyskinesia based on gender assessed over a 2‐year observational period since the start of levodopa treatment.
See this image and copyright information in PMC

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