| Summary: | Background and objective: Sex plays a role in Parkinson’s disease (PD) mechanisms. We analyzed sex difference manifestations among Spanish patients with PD. Patients and Methods: PD patients who were recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. A cross-sectional and a two-year follow-up analysis were conducted. Univariate analyses and general linear model repeated measure were used. Results: At baseline, data from 681 PD patients (mean age 62.54 ± 8.93) fit the criteria for analysis. Of them, 410 (60.2%) were males and 271 (39.8%) females. There were no differences between the groups in mean age (62.36 ± 8.73 vs. 62.8 ± 9.24; <i>p</i> = 0.297) or in the time from symptoms onset (5.66 ± 4.65 vs. 5.21 ± 4.11; <i>p</i> = 0.259). Symptoms such as depression (<i>p</i> < 0.0001), fatigue (<i>p</i> < 0.0001), and pain (<i>p</i> < 0.00001) were more frequent and/or severe in females, whereas other symptoms such as hypomimia (<i>p</i> < 0.0001), speech problems (<i>p</i> < 0.0001), rigidity (<i>p</i> < 0.0001), and hypersexuality (<i>p</i> < 0.0001) were more noted in males. Women received a lower levodopa equivalent daily dose (<i>p</i> = 0.002). Perception of quality of life was generally worse in females (PDQ-39, <i>p</i> = 0.002; EUROHIS-QOL8, <i>p</i> = 0.009). After the two-year follow-up, the NMS burden (Non-Motor Symptoms Scale total score) increased more significantly in males (<i>p</i> = 0.012) but the functional capacity (Schwab and England Activities of Daily Living Scale) was more impaired in females (<i>p</i> = 0.001). Conclusion: The present study demonstrates that there are important sex differences in PD. Long-term prospective comparative studies are needed.
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