When gender matters: Restless legs syndrome. Report of the “RLS and woman” workshop endorsed by the European RLS Study Group

Mauro Manconia, , , Jan Ulfbergb, Klaus Bergerc, Imad Ghorayebd, Jan Wesströme, Stephany Fuldaf, Richard P. Alleng, Thomas Pollmächerf, ha Sleep and Epilepsy Center, Neurocenter (EOC) of Southern Switzerland, Civic Hospital, Lugano, Via Tesserete 46, 6900 Lugano, Switzerlandb Department of Medicine, Uppsala University, Uppsala, Swedenc Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germanyd Clinical Neurophysiology Department, Centre Hospitalier et Universitaire de Bordeaux, Bordeaux cedex, Francee Center for Clinical Research Dalarna, Department of Women's and Children's Health, Uppsala University, Swedenf Max Planck Institute of Psychiatry, Munich, Germanyg Center of Mental Health, Klinikum Ingolstadt, Ingolstadt, Germanyh Department of Neurology, Johns Hopkins University, Bayview Medical Center, Baltimore, MD, USAReceived 13 May 2011. Revised 30 August 2011. Accepted 30 August 2011. Available online 9 November 2011.View full text Sleep is an essential human behavior that shows prominent gender differences. Disturbed sleep, in particular, is much more prevalent in females than males. Restless legs syndrome (RLS) as one cause of disturbed sleep was observed to be somewhat more common among women than men in Ekbom's 1945 seminal series of clinical cases with the disease. He, however, reported this gender difference mainly for those with more severe symptoms. Since then numerous studies have reported that women are affected by RLS about twice as often as males for mild as well as moderate to severe RLS. The present review focuses on RLS in females from the perspectives of both epidemiology and pathophysiology. RLS will generally become worse or might appear for the first time during pregnancy. Parity increases the risk of RLS later in life suggesting that pregnancy is a specific behavioral risk factor for developing RLS. Some evidence suggests that dysfunction in iron metabolism and high estrogen levels might contribute to RLS during pregnancy. But, menopause does not lower the incidence of RLS nor does hormone replacement therapy lead to an increase, suggesting a quite complex uncertain role of hormones in the pathophysiology of RLS. Therefore, further, preferably longitudinal studies are needed to unravel the factors causing RLS in women. These studies should include genetic, clinical and polysomnographic variables, as well as hormonal measures and variables assessing iron metabolism.

prs.rt("abs_end");Restless legs syndrome; Gender; Female; Sleep; Insomnia; Pregnancy; Estrogens; Menopause; Quality of life

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Fig. 1. Epidemiological results on RLS and pregnancy. Histograms show the prevalence trend of RLS in a group of 606 women surveyed at the end of pregnancy. In the period before pregnancy, 60 women already experienced RLS symptoms in their life (in a non pregnancy period) and were classified as “pre-existing RLS”. The remaining 546 women had never experienced RLS symptoms before and were classified as “healthy”. During the first assessed pregnancy (2nd histogram) 101 women, out of the 546 “healthy” ones, developed a transient RLS form strictly related to the pregnancy and were classified as “pregnancy-related RLS”. All these 101 women with a new form of pregnancy-related RLS form, except 6 women, recovered after delivery (3rd histogram). Fifty nine of the same pregnancy-related RLS group suffered again RLS symptoms during a further following pregnancy. After a mean follow up of 7 years, 25 out of the 101 women who experienced the symptoms during the first pregnancy (pregnancy-related RLS group) developed a chronic apparently idiopathic RLS form even out of pregnancy. Elaborated data from the study of Cesnik et al.37

View Within ArticleFig. 2. Prevalence of RLS among women in two age groups and according to number of children born in the German general practioner study.43

View Within ArticleFig. 3. Median serum ferritin by age for major USA gender and population groups.

View Within ArticleFig. 4. Prevalence of clinically significant RLS by gender and age from large European and United States population-based samples. (Slightly modified from Allen et al).21

View Within ArticleTable 1. Studies on the prevalence of RLS performed in random samples of the general population of different countries, using the IRLSSG criteria to assess the diagnosis.

View Within ArticleTable 2. Epidemiological studies published in literature on RLS prevalence that included an assessment on the quality of life.

Abbreviations: EQ-5D VAS, visual analogue scale score for the EQ-5D, a quality of life questionnaire developed by the EuroQoL Group; HRQoL, health related quality of life; MCS, mental component score of the SF-36; RLS, restless legs syndrome; PCS, physical component score of the SF-36; SF-36, SF-12, short form health survey.

View Within ArticleTable 3. Studies exploring the role of estrogens in RLS.

Abbreviations: AC, active controlled; CO, crossover; DB, double blind; HRT, hormone replacement therapy; IQR, interquartile range; PC, placebo controlled; PG, parallel group; PLM, periodic leg movements; R, randomized; SD, standard deviation.

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