Sex‐specific association of urate and levodopa‐induced dyskinesia in Parkinson’s disease

Abstract

Background and purpose As a major antioxidant, uric acid (UA) is known to be associated with the clinical progression of Parkinson’s disease (PD). This study investigated whether baseline UA levels are associated with the risk for levodopa‐induced dyskinesia (LID) in PD in a sex‐dependent manner. Methods In all, 152 patients with de novo PD (78 males and 74 females) who were followed up for >2 years were enrolled. The effect of baseline serum UA levels on LID‐free survival was assessed by Cox regression, separately for sex, whilst being adjusted for potential confounding factors. The optimal UA level cut‐off value to determine the high‐risk group for LID was set using Contal and O’Quigley’s method. Results Levodopa‐induced dyskinesia developed in 23 (29.5%) male patients and 30 (40.5%) female patients. Cox regression showed a significant interaction between UA level and sex. Higher UA levels were associated with a higher risk for LID in male PD patients (hazard ratio 1.380; 95% confidence interval 1.038–1.835; P = 0.027), although this relationship was not observed in female PD patients. The optimal UA level cut‐off for LID in male PD was 7.2 mg/dl, and the high UA group had a 5.7‐fold higher risk of developing LID than the low UA group. Conclusions Contrary to a presumptive beneficial role of UA, the present study demonstrated that higher UA levels are associated with increased risk of LID occurrence in male patients with PD, suggesting a sex‐dependent role of UA in LID.

Low serum uric acid levels and levodopa-induced dyskinesia in Parkinson's disease

“…34,35 In this sense, a previous study has not observed either relation of the risk of LID and UA levels in PD women. 11 Despite the literature, the results presented here suggest a relation between low UA levels and dyskinesia in PD women. In line with our results, an epidemiological cohort study suggested a slight inverse association between UA levels and the risk of DP in the female sex, but less significantly than in men 36 or only being observed after 8 years of follow-up.…”

“…However, a recent study that investigated the role of UA on LID in PD patients found an oppositive result, showing that higher serum UA levels are associated with increased risk of LID in men with PD. 11 Given the evidence about the relation of nigrostriatal depletion with UA and, with the appearance of LIDs, we hypothesize that lower serum UA levels are related with the presence of LID in PD patients. Additionally, we explored for possible associations among serum UA levels and clinical features of PD.…”

“…34 35 In this sense, a previous study has not observed either relation of the risk of LID and UA levels in PD women. 11…”

“…However, a recent study that investigated the role of UA on LID in PD patients found an oppositive result, showing that higher serum UA levels are associated with increased risk of LID in men with PD. 11…”

Anti-Hyperuricemic, Anti-Arthritic, Hemolytic Activity and Therapeutic Safety of Glycoconjugated Triazole-Phthalimides

“…Hyperuricemia can lead to complications such as heart failure, high blood pressure, kidney failure and diabetes mellitus [ 11 ]. In addition, several drugs used to treat other comorbidities can increase serum uric acid levels, such as diuretics, especially thiazides [ 12 ], immunosuppressants such as Ciclosporin [ 3 ], cytotoxic chemotherapy [ 13 ], and Levodopa [ 14 ], among other pharmaceutical formulations [ 15 , 16 ].…”