Why Are Women Prone to Restless Legs Syndrome?

Abstract

Restless legs syndrome is a relatively common neurologic disorder considerably more prevalent in women than in men. It is characterized by an inactivity-induced, mostly nocturnal, uncomfortable sensation in the legs and an urge to move them to make the disagreeable sensation disappear. Some known genes contribute to this disorder and the same genes contribute to an overlapping condition—periodic leg movements that occur during sleep and result in insomnia. Dopamine and glutamate transmission in the central nervous system are involved in the pathophysiology, and an iron deficiency has been shown in region-specific areas of the brain. A review of the literature shows that pregnant women are at particular risk and that increased parity is a predisposing factor. Paradoxically, menopause increases the prevalence and severity of symptoms. This implies a complex role for reproductive hormones. It suggests that changes rather than absolute levels of estrogen may be responsible for the initiation of symptoms. Both iron (at relatively low levels in women) and estrogen (at relatively high oscillating levels in women) influence dopamine and glutamate transmission, which may help to explain women’s vulnerability to this condition. The syndrome is comorbid with several disorders (such as migraine, depression, and anxiety) to which women are particularly prone. This implies that the comorbid condition or its treatment, or both, contribute to the much higher prevalence in women than in men of restless legs syndrome.

Grey matter alterations in restless legs syndrome: A coordinate‐based meta‐analysis

“…It has been reported that women are more prone to RLS, with it occurring about twice as frequently for women as for men in adults aged > 35 years (Allen et al., 2014; Manconi et al., 2012; Seeman, 2020). The underlying pathophysiology of preponderance of women in RLS remains unclear (Manconi et al., 2012; Seeman, 2020). Sex differences in human brain morphology have been consistently reported (Ruigrok et al., 2014).…”

Restless Leg Syndrome Is Underdiagnosed in Hereditary Hemorrhagic Telangiectasia—Results of an Online Survey

“…In this study, more female patients answered the survey. In general, women are also more prone to RLS than men [ 35 ]. In addition, regional differences in the prevalence of RLS exist.…”

Sleep Disorders in Pregnancy

“…Restless legs syndrome (RLS) or Willis-Ekbom disease is a motor-sensory disorder of the lower limbs associated with increased likelihood of sleep-wake disorders, such as poor sleep, poor daytime function and excessive daytime sleepiness in pregnancy. This condition is almost twice as common in women as in men, but reasons for this imbalance in prevalence are not precisely understood [76]. Indeed, the first known epidemiological study of RLS during pregnancy reported a prevalence of 11.3%, but in the third trimester prevalence appeared to rise up to 30%.…”

“…Other pharmacological agents, such as clonazepam, clonidine, and opioids may be needed in severe conditions, despite there is a high risk of neonatal withdrawal with these drugs [9,18]. Non-pharmacological treatments that can be used in pregnant women with RLS are physical exercise and behavioural strategies, such as reduced caffeine intake [76].…”