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 suggests an overlap between pain modulatory pathways and pathways of other sensory disturbances.
There is a complex relationship between estrogens, dopamine, and movement disorders in RLS [ 32 ]. Estrogen acts as a dopamine antagonist in schizophrenia [ 33 ] and this has been hypothesized as its role in RLS, but it may be changes in level rather than the absolute level that influence RLS expression [ 32 ].
The prevalence rises significantly during pregnancy as estrogen levels are rising and often first appears in women during pregnancy [ 34 , 35 ].
The meta-analysis of Makrani et al. The association with pregnancy is attributable not only to rising estrogen levels but also to falling iron levels during gestation. The more times a woman is pregnant, the higher the risk of RLS later in life. This strongly suggests that pregnancy is a specific risk factor for the development of RLS [ 37 ]. However, pregnancy hormones cannot be wholly responsible.
If high levels of estrogen triggered RLS, one would expect the rate or severity to diminish after menopause but this does not happen, nor does the use of hormone replacement therapy lead to an increased incidence [ 38 ]. Periodic limb movements, in fact, increase at menopause and are associated with vasomotor symptoms [ 39 ].
There is no statistical relationship between the use of hormone replacement therapy, the postmenopausal state and RLS [ 37 ].
There is considerable comorbidity of RLS with diseases that are particularly common in women [ 40 , 41 , 42 , 43 , 44 ], notably migraine, sleep disorder, depression, and anxiety [ 3 , 4 , 5 , 44 ]. The drugs that treat these disorders may, in fact, be the culprits [ 45 , 46 , 47 , 48 , 49 ], as is shown by the fact that RLS symptoms start within days of initiating treatment.
This may help to further explain the high prevalence of RLS in women relative to men. It is possible that a comorbid disease or its treatment serves as a trigger for the emergence of RLS.
The list of therapeutic drugs that can potentially exacerbate RLS is very long, as detailed by Zucconi et al. RLS is a treatable condition that generally responds well to pharmacologic therapy. A variety of treatments have been studied in randomized controlled trials, and treatment guidelines for RLS have been periodically revised [ 51 ].
The first-line treatments currently recommended are dopamine agonists [ 52 ], but also alphadelta calcium channel ligands such as gabapentin enacarbil, pregabalin, and gabapentin [ 2 ]. Other treatments include iron supplementation [ 53 , 54 ], benzodiazepines [ 55 ], and opioids [ 56 , 57 ]. In patients with mild symptoms, nonpharmacologic therapies may be sufficient. These include wearing sensible shoes, exercise and behavioral strategies, distraction through mental activities, reduced caffeine intake, and massage [ 58 ].
RLS is a common disorder about which there is relatively little consensus because no biomarker exists. There is considerable overlap with conditions whose symptoms are very similar. What makes demarcation especially difficult is that the description of the symptoms varies from person to person and, in addition, accepted diagnostic criteria undergo change over time.
To overcome some of the gaps in knowledge, one would need to amass a very large respondent sample of individuals of all ages from all parts of the world. Because the symptoms are subjective, what is needed is an extensive database of personal symptom descriptions. There exists an online survey method, the real-time interactive worldwide intelligence RIWI method, that is able to obtain responses to brief questions from large numbers of people in any geographic location that has internet access [ 59 ].
This method has proven to be quick and reliable. Sensitive questions can be asked because respondents remain anonymous. The method was recently used with great success by Harvard researchers to examine healthcare quality in 12 low- and middle-income countries [ 60 ]. It abates with movement.
RLS is a partially heritable disorder more prevalent in women than in men and commonly associated with periodic leg movements that occur during sleep and lead to insomnia. Symptoms overlap with those of drug-induced akathisia. Dopamine and glutamate transmission in the central nervous system is involved, as well as regional iron deficiency in the brain, though, in the idiopathic form of RLS, peripheral blood iron remains normal.
Pregnant women are at particular risk, and increased parity is a predisposing factor. This suggests a role for reproductive hormones except for the fact that menopause increases rates of occurrence, rather than decreasing them.
One hypothesis is that change in the level of hormones, rather than absolute levels, is responsible. A major contribution to the higher prevalence in women is likely to be the associated comorbidities such as migraine, depression, and anxiety. National Center for Biotechnology Information , U.
Published online Jan 6. Mary V. Author information Article notes Copyright and License information Disclaimer. Received Dec 3; Accepted Dec This article has been cited by other articles in PMC.
Abstract Restless legs syndrome is a relatively common neurologic disorder considerably more prevalent in women than in men. Keywords: restless legs syndrome, periodic limb movements, Willis—Ekbom disease, women.
Introduction Restless leg syndrome RLS or Willis—Ekbom disease is almost twice as common in women as it is in men but the reasons for this imbalance in prevalence are not precisely known.
Method The literature search was conducted by using the keywords restless legs syndrome, periodic limb movements, Willis—Ekbom disease, women as search terms and probing for them in PubMed and Google Scholar databases. Findings 3.
Making the Diagnosis RLS is a subjectively defined condition with diagnosis based on the following criteria: a the urge to move that emerges during periods of rest when sitting or lying down, and grows worse in the evening and at night and b uncomfortable sensations in the legs that are relieved by movement. Epidemiology Because the definition of RLS is subjective and under-reported, its exact prevalence remains inaccurately known. Genetics Twin studies and familial aggregation analysis estimate the heritability of RLS to be between Pathophysiology The pathophysiology of RLS is contested at present.
Estrogens There is a complex relationship between estrogens, dopamine, and movement disorders in RLS [ 32 ]. Comorbidity There is considerable comorbidity of RLS with diseases that are particularly common in women [ 40 , 41 , 42 , 43 , 44 ], notably migraine, sleep disorder, depression, and anxiety [ 3 , 4 , 5 , 44 ]. Treatment RLS is a treatable condition that generally responds well to pharmacologic therapy. But in up to two out of every five cases, the symptoms of RLS begin before age According to a review published in January in the International Journal of Environmental Research and Public Health , changes in hormone levels may play a role in explaining why women are more vulnerable to RLS.
This theory is based on the fact that both pregnancy and menopause appear to increase rates of occurrence. Another theory is that the higher prevalence in women is because RLS is comorbid with several disorders to which women are particularly prone, such as migraines , depression, and anxiety. RLS is common during pregnancy, particularly in the last trimester. Many people with RLS also experience uncontrollable, repetitive leg movements that occur while they are relaxed, drowsy, or sleeping.
When these movements occur during sleep, they are called periodic limb movements of sleep PLMS. When these occur while a person is awake, they are called periodic limb movements of wakefulness PLMW. RLS can cause exhaustion and daytime sleepiness, which can have a negative effect on mood, contributing to depression and anxiety. It can also affect your ability to perform well at school or at work. Untreated moderate to severe RLS can lead to a 20 percent decrease in work productivity.
American Sleep Association ASA This group was founded by physicians and scientists in with a mission to increase the awareness of the importance of sleep and the harmful effects of sleep disorders. National Sleep Foundation This foundation dedicates itself to improving health and well-being through sleep education and advocacy.
Editorial Sources and Fact-Checking. Cleveland Clinic. January 1, Restless Legs Syndrome Fact Sheet. March 17, September 18, Restless Leg Syndrome. Disease InfoSearch. Howard H, Kamat D. Restless Legs Syndrome in Children. Pediatric Annals. And you might attribute these movements to restlessness, nervousness, or stress.
A more severe case of RLS is challenging to ignore. It can complicate the simplest activities, like going to the movies. A long plane ride can also be difficult. People with RLS are likely to have trouble falling asleep or staying asleep because symptoms are worse at night.
Daytime sleepiness, fatigue, and sleep deprivation can harm your physical and mental health. Symptoms usually affect both sides of the body, but some people have them on only one side. In mild cases, symptoms may come and go. RLS can also affect other parts of the body, including your arms and head.
For most people with RLS, symptoms worsen with age. People with RLS often use movement as a way to relieve symptoms. That might mean pacing the floor or tossing and turning in bed.
If you sleep with a partner, it may well be disturbing their sleep as well. More often than not, the cause of RLS is a mystery. There may be a genetic predisposition and an environmental trigger. More than 40 percent of people with RLS have some family history of the condition. In fact, there are five gene variants associated with RLS.
When it runs in the family, symptoms usually start before age There may be a connection between RLS and low levels of iron in the brain, even when blood tests show that your iron level is normal. RLS may be linked to a disruption in the dopamine pathways in the brain. Some of the same medications are used to treat both conditions. Research on these and other theories is ongoing. Other potential causes include medications to treat:. But RLS can actually be an offshoot of another health problem, like neuropathy, diabetes, or kidney failure.
Learn more about the causes of restless leg syndrome ». There are certain things that may put you in a higher risk category for RLS. Having RLS can affect your overall health and quality of life.
If you have RLS and chronic sleep deprivation, you may be a higher risk of:. A large part of the diagnosis will be based on your description of symptoms. Your doctor will want to check for other neurological reasons for your symptoms. Be sure to provide information about any over-the-counter and prescription medications and supplements you take.
And tell your doctor if you have any known chronic health conditions. Blood tests will check for iron and other deficiencies or abnormalities. Home remedies, while unlikely to completely eliminate symptoms, may help reduce them.
It may take some trial and error to find the remedies that are most helpful. When scheduling things that require prolonged sitting, such as a car or plane trip, try to arrange them for earlier in the day rather than later.
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