Idiopathic restless legs syndrome treatment: Progress and pitfalls?

The pathophysiology of Restless Legs Syndrome (RLS) remains uncertain. Although the dopaminergic and/or the iron breakdown homeostasis hypotheses are still considered to be the mainstay of the RLS underlying mechanism, therapeutic intervention aiming to alleviate RLS syndrome through dopamine agonists use and iron stores recovery failed so far to show short-term remarkable efficacy, and controlled trials to establish sustained long-term efficacy, tolerability and safety are lacking. Here we review available literature dealing with pharmacological treatment of RLS and consider some rational aspects of RLS pathophysiology that may support the use of available drug classes in treating this condition.

When gender matters: restless legs syndrome. Report of the "RLS and woman" workshop endorsed by the European RLS Study Group.

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.