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. 2025 Apr;34(2):e14311.
doi: 10.1111/jsr.14311. Epub 2024 Aug 19.

Sex-based disparities in dopamine agonist response in patients with restless legs syndrome

Maria P Mogavero  1   2 , Elena Antelmi  3   4 , Giuseppe Lanza  5   6 , Sara Marelli  1   2 , Alessandra Castelnuovo  1   2 , Michele Tinazzi  3   7 , Lourdes M DelRosso  8 , Rosalia Silvestri  9 , Raffaele Ferri  5 , Luigi Ferini Strambi  1   2
Affiliations

Sex-based disparities in dopamine agonist response in patients with restless legs syndrome

Maria P Mogavero et al. J Sleep Res. 2025 Apr.

Abstract

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 D3, 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.

Keywords: dopamine agonists; isolated leg movements during sleep; periodic leg movements during sleep; restless legs syndrome; sex.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Distribution of inter‐movement intervals obtained at baseline and during the treatment night in females and males.
See this image and copyright information in PMC

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References

    1. Allen, R. , Becker, P. M. , Bogan, R. , Schmidt, M. , Kushida, C. A. , Fry, J. M. , Poceta, J. S. , & Winslow, D. (2004). Ropinirole decreases periodic leg movements and improves sleep parameters in patients with restless legs syndrome. Sleep, 27(5), 907–914. 10.1093/sleep/27.5.907 - DOI - PubMed
    1. Allen, R. P. , Picchietti, D. L. , Garcia‐Borreguero, D. , Ondo, W. G. , Walters, A. S. , Winkelman, J. W. , Zucconi, M. , Ferri, R. , Trenkwalder, C. , Lee, H. B. , & International Restless Legs Syndrome Study, Group . (2014). Restless legs syndrome/Willis–Ekbom disease diagnostic criteria: Updated international restless legs syndrome study group (IRLSSG) consensus criteria – history, rationale, description, and significance. Sleep Medicine, 15(8), 860–873. 10.1016/j.sleep.2014.03.025 - DOI - PubMed
    1. Bao, A.‐M. , & Swaab, D. F. (2010). Sex differences in the brain, behavior, and neuropsychiatric disorders. The Neuroscientist, 16(5), 550–565. - PubMed
    1. Bassetti, C. L. A. , Randerath, W. , Vignatelli, L. , Ferini‐Strambi, L. , Brill, A. K. , Bonsignore, M. R. , Grote, L. , Jennum, P. , Leys, D. , Minnerup, J. , Nobili, L. , Tonia, T. , Morgan, R. , Kerry, J. , Riha, R. , McNicholas, W. T. , & Papavasileiou, V. (2020). EAN/ERS/ESO/ESRS statement on the impact of sleep disorders on risk and outcome of stroke. The European Respiratory Journal, 55(4), 1901104. 10.1183/13993003.01104-2019 - DOI - PubMed
    1. Bliwise, D. L. , Freeman, A. , Ingram, C. D. , Rye, D. B. , Chakravorty, S. , & Watts, R. L. (2005). Randomized, double‐blind, placebo‐controlled, short‐term trial of ropinirole in restless legs syndrome. Sleep Medicine, 6(2), 141–147. 10.1016/j.sleep.2004.12.002 - DOI - PubMed

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