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Background <p>Non-motor symptoms (NMSs) are highly prevalent in Parkinson’s disease (PD) and affect patients’ quality of life. Data on gender differences in NMSs are largely cross-sectional and derived from chronically treated populations. Longitudinal evidence in early, levodopa-naïve PD patients remains limited. This study aims to longitudinally investigate gender differences in a wide range of NMSs in early-stage levodopa-naïve PD patients during the first 2&#xa0;years following levodopa initiation.</p> Methods <p>This multicenter, prospective study enrolled 216 levodopa-naïve PD patients (139 men, 77 women) from 17 Italian movement disorder centers. Patients were evaluated at baseline and after 24&#xa0;months (24&#xa0;M) using validated scales. Baseline gender differences were explored using group comparisons. Gender effects at 24&#xa0;M were examined using ANCOVA models adjusted for baseline values and levodopa dose at follow-up.</p> Results <p>At baseline, women showed greater cardiovascular and thermoregulatory autonomic dysfunction, higher anxiety, pain, fatigue, and worse quality of life, whereas men exhibited greater sexual dysfunction, daytime sleepiness, and better attentional performance. At the 24&#xa0;M, gender differences persisted only for anxiety, pain, mobility, and emotional well-being, while additional significant differences emerged, including hypersexuality, visuo- spatial domain, and orthostatic-hypotension. Women exhibited greater symptom severity than men across all aforementioned variables, with the exception of hypersexuality.</p> Conclusions <p>Gender significantly influences the expression and early evolution of NMSs in PD, independently of levodopa exposure. Gender-specific NMSs profiles are already evident in the first two years of treatment. These findings highlight the importance of integrating gender considerations into early assessment and personalized management of NMSs in PD.</p>

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Gender differences in non-motor symptoms in Parkinson’s disease: a multicenter longitudinal study

  • 期刊论文

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  • 发表日期：

    2026年4月16日

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  • Sofia Cuoco,
  • Michela Russo,
  • Marina Picillo,
  • Carlo Ricciardi,
  • Maria Claudia Russillo,
  • Marianna Amboni,
  • Gennarina Arabia,
  • Laura Avanzino,
  • Margherita Canesi,
  • Alessia Catania,
  • Roberto Ceravolo,
  • Calogero Edoardo Cicero,
  • Roberto Cilia,
  • Isabel Colangelo,
  • Giovanna Dati,
  • Rosa De Micco,
  • Anna De Rosa,
  • Alessio Di Fonzo,
  • Roberto Eleopra,
  • Vincenza Fetoni,
  • Barbara Garavaglia,
  • Augusta Giglio,
  • Martina Giuntini,
  • Federica Invernizzi,
  • Giulia Lazzeri,
  • Roberta Marchese,
  • Alessandra Nicoletti,
  • Claudio Pacchetti,
  • Celeste Panteghini,
  • Manuela Pilleri,
  • Fabiana Giada Radicati,
  • Chiara Reale,
  • Cesa Scaglione,
  • Andrea Soricelli,
  • Fabrizio Stocchi,
  • Alessandro Tessitore,
  • Laura Vacca,
  • Maria Antonietta Volontè,
  • Graziella Volpi,
  • Roberta Zangaglia,
  • Francesco Amato,
  • Paolo Barone,
  • Maria Teresa Pellecchia

摘要

Background

Non-motor symptoms (NMSs) are highly prevalent in Parkinson’s disease (PD) and affect patients’ quality of life. Data on gender differences in NMSs are largely cross-sectional and derived from chronically treated populations. Longitudinal evidence in early, levodopa-naïve PD patients remains limited. This study aims to longitudinally investigate gender differences in a wide range of NMSs in early-stage levodopa-naïve PD patients during the first 2 years following levodopa initiation.

Methods

This multicenter, prospective study enrolled 216 levodopa-naïve PD patients (139 men, 77 women) from 17 Italian movement disorder centers. Patients were evaluated at baseline and after 24 months (24 M) using validated scales. Baseline gender differences were explored using group comparisons. Gender effects at 24 M were examined using ANCOVA models adjusted for baseline values and levodopa dose at follow-up.

Results

At baseline, women showed greater cardiovascular and thermoregulatory autonomic dysfunction, higher anxiety, pain, fatigue, and worse quality of life, whereas men exhibited greater sexual dysfunction, daytime sleepiness, and better attentional performance. At the 24 M, gender differences persisted only for anxiety, pain, mobility, and emotional well-being, while additional significant differences emerged, including hypersexuality, visuo- spatial domain, and orthostatic-hypotension. Women exhibited greater symptom severity than men across all aforementioned variables, with the exception of hypersexuality.

Conclusions

Gender significantly influences the expression and early evolution of NMSs in PD, independently of levodopa exposure. Gender-specific NMSs profiles are already evident in the first two years of treatment. These findings highlight the importance of integrating gender considerations into early assessment and personalized management of NMSs in PD.