Bentall Lily M, Parr-Brownlie Louise C
Department of Anatomy, University of Otago, Dunedin, New Zealand.
Eur J Neurosci. 2025 May;61(9):e70144. doi: 10.1111/ejn.70144.
Sexual dimorphism is well-documented in Parkinson's disease (PD); however, when it comes to levodopa-induced dyskinesia (LID), epidemiological and clinical findings are scarce. This is an oversight because recent studies show significant correlations between LID risk and female sex. Estrogen strongly impacts neuronal function, affecting cognitive tasks such as movement, object recognition, and reward. In movement pathways, estrogen increases dopamine synthesis, transmission, and regulation, resulting in neuroprotection for PD in women. However, following menopause, PD prevalence, symptom severity, and LID risk increase for women. Consequently, early to mid-life estrogen state is neuroprotective, but later in life becomes a risk factor for PD and LID. This review explores estrogen's action in the brain, specifically within the dopamine system. Sexual dimorphism is described for the prevalence and onset of PD and LID. We examine the cellular basis of estrogen's role in sexual dimorphism and integrate these ideas to hypothesize why the risk for LID is higher for women, than men, with PD. Lastly, this review proposes that women with PD need their symptoms to be considered and managed differently to males. Treatment of women with PD should be based on their menopausal stage, as estrogen may be masking, exacerbating, or complicating symptoms. Importantly, we present these concepts to stimulate discussion among clinical and bench scientists so that key experiments can be conducted to examine the mechanisms underlying LID, so they can be prevented to improve the quality of life for women and men living with PD in the future.
帕金森病（PD）中的性别二态性已有充分记录；然而，关于左旋多巴诱导的异动症（LID），流行病学和临床研究结果却很匮乏。这是一个疏忽，因为最近的研究表明LID风险与女性性别之间存在显著相关性。雌激素强烈影响神经元功能，影响诸如运动、物体识别和奖赏等认知任务。在运动通路中，雌激素增加多巴胺的合成、传递和调节，从而对女性的帕金森病起到神经保护作用。然而，绝经后，女性的帕金森病患病率、症状严重程度和LID风险都会增加。因此，中年早期的雌激素状态具有神经保护作用，但在生命后期却成为帕金森病和LID的一个风险因素。本综述探讨雌激素在大脑中的作用，特别是在多巴胺系统中的作用。描述了帕金森病和LID患病率及发病的性别二态性。我们研究了雌激素在性别二态性中作用的细胞基础，并整合这些观点来推测为什么帕金森病女性比男性发生LID的风险更高。最后，本综述提出，帕金森病女性的症状需要与男性区别对待和管理。帕金森病女性的治疗应基于其绝经阶段，因为雌激素可能会掩盖、加重或使症状复杂化。重要的是，我们提出这些概念以激发临床科学家和基础科学家之间的讨论，以便能够开展关键实验来研究LID的潜在机制，从而在未来预防LID，提高帕金森病患者的生活质量。
