Melatonin secretion in patients with Parkinson's disease receiving different-dose levodopa therapy

Objective: Melatonin is involved in the regulation of sleep and circadian biological rhythmicity; decreased melatonin secretion has been associated with circadian disruptions. Previous studies evalu-ating melatonin levels between patients with Parkinson's disease (PD) and controls without PD have found conflicting results; however, large-scale studies have not been performed. Our aim is to compare endogenous melatonin levels between patients with Parkinson's disease (PD) and non-PD older adults. Methods: In this cross-sectional study on 201 outpatients with PD and 380 community-dwelling older Japanese adults (controls), urinary 6-sulfatoxymelatonin excretion was measured to estimate endogenous melatonin levels. Results: Urinary 6-sulfatoxymelatonin excretion (UME) did not significantly differ overall between PD patients and non-PD controls, even after adjusting for age, gender, medications, sleep habits, and seasons. Among PD patients, a clear and robust dose-response association was found between levodopa equivalent dose and UME, independent of potential confounding factors, including Parkinson's disease severity. Compared with the lowest levodopa equivalent dose quartile group (mean levodopa equivalent dose, 132 mg/day), the highest group (mean levodopa equivalent dose, 973 mg/day) exhibited a 68% increase in UME (17.8 vs. 30.0 ng/mg cre, respectively). In addition, compared with the non-PD controls, PD patients receiving a lower levodopa equivalent dose displayed decreased UME and those receiving higher levodopa equivalent dose displayed increased UME. Conclusion: Our study suggests that melatonin levels in PD patients receiving average levodopa doses are comparable with those in older adults, even after considering confounding factors. This association was modulated by daily levodopa dose in PD patients. (c) 2020 Elsevier B.V. All rights reserved.