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

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. 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. 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. 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.

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Publication Details

Journal
Neurological Sciences
Published
2026-04-16
DOI
https://doi.org/10.1007/s10072-026-09031-2
Primary Topic
Parkinson's Disease Mechanisms and Treatments
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Martina Giuntini, Margherita Canesi, Giulia Lazzeri, Isabel Colangelo et al.
Neurological Sciences
Parkinson's Disease Mechanisms and Treatments
article

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

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

Abstract

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. 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. 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. 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.

Neurological SciencesVol. 47(5)
University of Pisa (IT), Synlab Czech (Czechia) (CZ), University of Salerno (IT), Vita-Salute San Raffaele University (IT), University of Campania "Luigi Vanvitelli" (IT), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), San Raffaele University of Rome (IT), Magna Graecia University (IT), University of Catania (IT), Ospedale Maggiore (IT), Moriggia Pelascini Hospital (IT), Parkinson's UK (GB), Ospedale Sant'Anna (IT), Federico II University Hospital (IT), Istituto delle Scienze Neurologiche di Bologna (IT), IRCCS Ospedale San Raffaele (IT), Metropolitana Milanese (Italy) (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), ASST Fatebenefratelli Sacco (IT), Fondazione IRCCS Istituto Neurologico Carlo Besta (IT), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT), University of Naples Federico II (IT), University of Genoa (IT)
Università degli Studi di Salerno, Agenzia Italiana del Farmaco, Ministero della Salute
Gender equality
Openalex Percentile: Top 17%
Parkinson's Disease Mechanisms and Treatments
DOIOpen Access PDFOpenAlex
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