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.