Mogavero Maria P, Antelmi Elena, Lanza Giuseppe, Marelli Sara, Castelnuovo Alessandra, Tinazzi Michele, DelRosso Lourdes M, Silvestri Rosalia, Ferri Raffaele, Ferini Strambi Luigi
Vita-Salute San Raffaele University, Milan, Italy.
Sleep Disorders Center, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
J Sleep Res. 2025 Apr;34(2):e14311. doi: 10.1111/jsr.14311. Epub 2024 Aug 19.
This study aimed to investigate sex-related differences in the response to ropinirole and pramipexole in patients with restless legs syndrome (RLS). By analysing clinical parameters and polysomnographic (PSG) findings, we sought to elucidate the potential factors related to sex disparities modulating treatment responses and sleep quality in RLS. A total of 41 drug-free patients with RLS, aged ≥18 years, underwent two consecutive nocturnal PSG recordings, without medication at baseline; before the second night, 26 patients received an oral dose of 0.25 mg pramipexole whereas 15 received 0.5 mg ropinirole. After each PSG recording, patients self-evaluated the severity of their previous night symptoms by means of an ad hoc visual analogue scale (VAS). At baseline, sleep efficiency and percentage of Stage N2 tended to be higher in females while wakefulness after sleep onset was significantly higher in males. After treatment, total leg movements during sleep (LMS), periodic LMS (PLMS), and periodicity indexes were significantly lower in females than in males. The VAS score was lower after treatment in all patients, without differences between the two sexes. This study demonstrates a higher acute responsiveness of PLMS to dopamine agonists (pramipexole and ropinirole) in females than in males with RLS. These findings might be explained by differential sex-related expression of dopamine receptors, especially D, within the central nervous system. In addition, our findings provide translational hints toward a better tailored and sex-specific approach to the treatment of RLS associated with PLMS, with dopamine agonist possibly associated with a better outcome in females than in males.
本研究旨在调查不安腿综合征（RLS）患者对罗匹尼罗和普拉克索反应的性别差异。通过分析临床参数和多导睡眠图（PSG）结果，我们试图阐明与性别差异相关的潜在因素，这些因素调节RLS患者的治疗反应和睡眠质量。共有41名年龄≥18岁的无药物治疗的RLS患者，在基线时未用药，连续进行了两次夜间PSG记录；在第二个晚上之前，26名患者口服0.25mg普拉克索，而15名患者口服0.5mg罗匹尼罗。每次PSG记录后，患者通过专门的视觉模拟量表（VAS）对前一晚症状的严重程度进行自我评估。在基线时，女性的睡眠效率和N2期百分比往往较高，而男性的睡眠后觉醒则明显较高。治疗后，女性睡眠期间的总腿部运动（LMS）、周期性LMS（PLMS）和周期性指数显著低于男性。所有患者治疗后的VAS评分均较低，两性之间无差异。本研究表明，女性RLS患者的PLMS对多巴胺激动剂（普拉克索和罗匹尼罗）的急性反应性高于男性。这些发现可能是由于中枢神经系统内多巴胺受体，尤其是D受体的性别相关差异表达所致。此外，我们的发现为更好地定制针对与PLMS相关的RLS的性别特异性治疗方法提供了转化线索，多巴胺激动剂可能使女性的治疗效果优于男性。
