• Brendan Bryan Jen-Wei Tan, Aaron Shengting Mai, Selene Joon-Yan Lee, and Eng-King Tan.
• Department of Neurology, Singapore General Hospital Campus, National Neuroscience Institute, Singapore, Singapore.
• Am. J. Med. Sci. 2024 Apr 1; 367 (4): 251258251-258.

BackgroundTamoxifen is widely used for hormone-sensitive breast cancer, achieved by modulating the estrogen receptor activity in a tissue-specific manner. There is evidence to support the protective effects of estrogen against Parkinson's disease (PD), a common neurodegenerative condition. Some epidemiologic studies suggest the use of tamoxifen may modulate the PD risk. We conducted a meta-analysis to examine the association between tamoxifen and risk of PD.MethodsA search of PubMed using search terms synonymous with "tamoxifen" and "Parkinson's disease" was conducted. Outcomes of interest were the odds ratio (OR) of PD comparing tamoxifen-exposed to -unexposed women, as well as the incidence rate of PD in tamoxifen-exposed women.ResultsA total of 37,932 subjects with breast cancer, comprising 17,233 tamoxifen-exposed subjects and 20,699 tamoxifen-unexposed subjects, satisfied the inclusion criteria. The exposure to tamoxifen ranged from 30-96 months. Using the common-effect model, the pooled OR of PD was 2.4, with (95% CI 1.91-3.01, P < 0.0001), with high heterogeneity (I2 = 81.5%, Cochran's Q test P = 0.001). Pooling 28,640 tamoxifen-exposed patients under the common-effect model found an incidence rate of 5.86 events per 10,000 person-years (95% CI 4.82-7.12) with minimal heterogeneity (I2 = 26%, Cochran's Q test P = 0.258).ConclusionsOur meta-analysis suggests that tamoxifen use may be associated with an increased PD risk in women. However, due to heterogeneity and potential limitations of some of the studies, further clinical and functional validation will be needed. Longitudinal studies supported by imaging and biomarkers evaluation will be useful to identify the mechanisms linking tamoxifen and PD risk.Copyright © 2023 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

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