Department of Neurology, Singapore General Hospital Campus, National Neuroscience Institute, Singapore, Singapore.
Department of Neurology, Singapore General Hospital Campus, National Neuroscience Institute, Singapore, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Am J Med Sci. 2024 Apr;367(4):251-258. doi: 10.1016/j.amjms.2023.11.003. Epub 2023 Nov 20.
Tamoxifen 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.
A 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.
A 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 (I = 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 (I = 26%, Cochran's Q test P = 0.258).
Our 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.
他莫昔芬被广泛用于激素敏感性乳腺癌，通过组织特异性调节雌激素受体活性来实现。有证据支持雌激素对帕金森病（PD）的保护作用，PD 是一种常见的神经退行性疾病。一些流行病学研究表明，他莫昔芬的使用可能会调节 PD 风险。我们进行了一项荟萃分析，以检查他莫昔芬与 PD 风险之间的关联。
使用同义词“他莫昔芬”和“帕金森病”对 PubMed 进行搜索。感兴趣的结果是比较暴露于他莫昔芬的女性与未暴露于他莫昔芬的女性 PD 的优势比（OR），以及暴露于他莫昔芬的女性 PD 的发病率。
共有 37932 名患有乳腺癌的患者符合纳入标准，其中 17233 名暴露于他莫昔芬，20699 名未暴露于他莫昔芬。他莫昔芬的暴露时间从 30 到 96 个月不等。使用共同效应模型，PD 的汇总 OR 为 2.4，（95%CI 1.91-3.01，P < 0.0001），存在高度异质性（I = 81.5%，Cochran's Q 检验 P = 0.001）。在共同效应模型下，对 28640 名暴露于他莫昔芬的患者进行汇总，发现发病率为每 10000 人年 5.86 例（95%CI 4.82-7.12），异质性极小（I = 26%，Cochran's Q 检验 P = 0.258）。
我们的荟萃分析表明，他莫昔芬的使用可能与女性 PD 风险增加有关。然而，由于存在异质性和一些研究的潜在局限性，还需要进一步的临床和功能验证。有影像学和生物标志物评估支持的纵向研究将有助于确定将他莫昔芬与 PD 风险联系起来的机制。
