BackgroundDespite its relevance, the clinical progression of motor- and non-motor symptoms associated with Parkinson's disease (PD) is poorly described and understood, particularly in relation to sex-specific differences in clinical progression.ObjectiveIdentification of differential aspects in disease progression in men and women with PD.MethodsLinear mixed-model analyses of 802 people with typical PD from the Luxembourg Parkinson's study's prospective cohort (median time of follow-up = three years). We estimated the effect of time and its moderation by sex (alpha ≤ 0.05), including confidence intervals, for the following outcomes: MDS-UPDRS I-IV, Starkstein Apathy Scale, Beck Depression Inventory, Montreal Cognitive Assessment (MoCA), Sniffin' sticks, bodily discomfort, rapid eye movement sleep behavior disorder questionnaire, PD Sleep Scale (PDSS), Munich Dysphagia Test-PD, Functional Mobility Composite Score, and the MDS-based tremor and postural instability and gait disturbances scale. In addition, the marginal means illustrated the symptoms' trajectories in men and women. Men and women had similar age.ResultsOverall, we observed a slower progression (interaction effect) in women compared to men, especially for MoCA (-0.159, 95%CI [-0.272, -0.046], p = 0.006), PDSS (-0.716, 95%CI [-1.229, -0.203], p = 0.006), PIGD (0.133, 95%CI [0.025 0.241], p = 0.016), and MDS-UPDRS II (0.346, 95%CI [0.120, 0.572], p = 0.003). The finding for MDS-UPDRS II was significant (FWER of 5%) after adjustment for multiple comparisons (Bonferroni-Holm).ConclusionsNext to the further exploration of sex-specific progression, interventions, proactive monitoring and communication strategies tailored to the symptoms progression and needs of men and women need to be developed.