Transient Willis-Ekbom's disease (restless legs syndrome) during pregnancy may be caused by estradiol-mediated dopamine overmodulation

Willis-Ekbom's disease (WED), formerly called restless legs syndrome, is more common in pregnant than in non-pregnant women, implying that the physiological and biochemical changes during pregnancy influence its development. During pregnancy, many hormone levels undergo significant changes, and some hormones significantly increase in activity and can interfere with other hormones. For example, the steroid hormone estradiol interferes with the neuroendocrine hormone dopamine. During pregnancy, the activity of the thyroid axis is enhanced to meet the increased demand for thyroid hormones during this state. Dopamine is a neuroendocrine hormone that diminishes the levels of thyrotropin and consequently of thyroxine, and one of the roles of the dopaminergic system is to counteract the activity of thyroid hormones. When the activity of dopamine is not sufficient to modulate thyroid hormones, WED may occur. Robust evidence in the medical literature suggests that an imbalance between thyroid hormones and the dopaminergic system underpins WED pathophysiology. In this article, we present evidence that this imbalance may also mediate transient WED during pregnancy. It is possible that the main hormonal alteration responsible for transient WED of pregnancy is the excessive modulation of dopamine release in the pituitary stalk by estradiol. The reduced quantities of dopamine then cause decreased modulation of thyrotropin, leading to enhanced thyroid axis activity and subsequent WED symptoms. Iron deficiency may also be a predisposing factor for WED during pregnancy, as it can both diminish dopamine and increase thyroid hormone.