When gender matters: Restless Legs Syndrome. Report of the “RLS and Woman” workshop endorsed by the European RLS Study Group

Sleep and Epilepsy Center, Neurocenter (EOC) of Southern Switzerland, Civic Hospital, Lugano, Via Tesserete 46, 6900 Lugano, Switzerland.
Sleep Medicine Reviews (Impact Factor: 8.51). 11/2011; 16(4):297-307. DOI: 10.1016/j.smrv.2011.08.006
Source: PubMed


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.

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    • "From a pathophysiological point of view, respiratory events in female subjects may be less severe, with more common partial upper-airway obstruction accounting for the differential impact on EDS (Anttalainen et al., 2007). RLS Similarly to what has been observed in relation to migraines, RLS has been associated with high estrogen levels (Manconi et al., 2012). Accordingly, it is well known that RLS is more common in women than in men (Berger et al., 2004). "

    Full-text · Article · Sep 2015 · Archives italiennes de biologie
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    • "Restless legs syndrome (RLS) affects 4%–14% of the adult population, depending on the rigorousness of the definition applied.1 It is twice as common in women, and has a prevalence of 2% in the pediatric population.2,3 RLS is a sensorimotor disorder, in which there is an irresistible urge to move the leg, although it can progress to involve other parts of the body, including the arms, trunk, and head.4 "
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    ABSTRACT: Gabapentin enacarbil XR is a new extended-release formulation which attempts to overcome the reduced efficacy of shorter-acting gabapentin, with sustained delivery over a 24-hour period. It is a gabapentin prodrug which is efficiently and rapidly converted to gabapentin during active transport throughout the length of the intestine via high-capacity monocarboxylate type 1 nutrient transporters unlike its predecessor, which is absorbed via low-capacity transporters largely confined to the upper intestinal region. Its lack of saturable absorption allows for dose-proportional absorption and hence increased bioavailability. Several clinical trials addressing its efficacy in moderate to severe restless legs syndrome (RLS) demonstrate improvements in the International RLS Rating Scale after a 2-week to 3-month period. Open-label studies of 52 weeks' duration showed maintenance of symptom reduction with once-daily administration of the extended-release formulation. The most commonly reported treatment-emergent adverse effects were somnolence and dizziness. Although the incidence of emergent adverse effects is high, it is comparable with that of gabapentin. No studies thus far have documented augmentation as an issue, unlike that observed with most dopaminergic agents. In addition, both dopamine precursors and agonists have not been shown to increase slow wave sleep or improve overall sleep architecture consistently despite improvement in the periodic leg movement index, in contrast with gabapentin enacarbil. Presently, gabapentin enacarbil has not been approved by the Therapeutic Goods Administration or Medsafe for use in RLS. The cost of this medication may also be a potential barrier for many patients. Future comparative efficacy studies with gabapentin, first-line dopaminergic agents, rotigotine, being the other once daily RLS medication, and pregabalin, the structural analog of gabapentin, will be necessary.
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    ABSTRACT: Sleep disorders affect women differently than they affect men and may have different manifestations and prevalences. With regard to obstructive sleep apnea (OSA), variations in symptoms may cause misdiagnoses and delay of appropriate treatment. The prevalence of OSA appears to increase markedly after the time of menopause. Although OSA as defined by the numbers of apneas/hypopneas may be less severe in women, its consequences are similar and perhaps worse. Therapeutic issues related to gender should be factored into the management of OSA. The prevalence of insomnia is significantly greater in women than in men throughout most of the life span. The ratio of insomnia in women to men is approximately 1.4:1.0, but the difference is minimal before puberty and increases steadily with age. Although much of the higher prevalence of insomnia in women may be attributable to the hormonal or psychological changes associated with major life transitions, some of the gender differences may result from the higher prevalence of depression and pain in women. Insomnia's negative impact on quality of life is important to address in women, given the high relative prevalence of insomnia as well as the comorbid disorders in this population. Gender differences in etiology and symptom manifestation in narcolepsy remain understudied in humans. There is little available scientific information to evaluate the clinical significance and specific consequences of the diagnosis of narcolepsy in women. Restless legs syndrome (RLS) is characterized by an urge to move the legs or other limbs during periods of rest or inactivity and may affect as much as 10% of the population. This condition is more likely to afflict women than men, and its risk is increased by pregnancy. Although RLS is associated with impaired quality of life, highly effective treatment is available.
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