Estrogen-associated migraine

Author Anne H Calhoun, MD Section Editors Robert L Barbieri, MDJerry W Swanson, MD Deputy Editor Vanessa A Barss, MD

INTRODUCTION A decline in estrogen concentration is an important factor in triggering migraine in women [1]. Estrogen-associated migraine refers to migraine headaches that occur when there is a decline in estrogen concentration after exposure to high levels of the hormone for several days (estrogen priming), as in the following settings [2,3]: Natural declines in endogenous estrogen, such as at the beginning of the menstrual cycle (figure 1) or postpartum. Scheduled withdrawal from exogenous estrogen-containing products, such as during the hormone-free interval in users of cyclic estrogen-progestin contraceptives (pills, transdermal patch, ring) or with interruptions in estrogen therapy. Unintentional estrogen withdrawal, such as from missed doses of estrogen-containing drugs or as a result of drug interactions that reduce availability.

Estrogen-associated migraine, primarily menstrual migraine, will be reviewed here. The pathophysiology, clinical manifestations and diagnosis of migraine and treatment of nonestrogenwithdrawal migraine are discussed separately. (See "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults" and "Acute treatment of migraine in adults".) Headaches (including migraine) in pregnant women and use of estrogen-containing contraceptives in women with preexisting migraine headache are also discussed elsewhere. (See "Headache in pregnancy" and "Risks and side effects associated with estrogen-progestin contraceptives", section on 'Migraine headaches'.) PATHOPHYSIOLOGY Estrogen has several important actions in the central nervous system that may account for its association with migraine [4]. The predominant effects are facilitation of the serotonergic and glutamatergic systems. Serotonergic tone in women is positively correlated with estrogen levels. When estrogen concentrations decline, serotonin concentrations also fall due to a decline in production coupled with an increased rate of elimination. The resultant decline in serotonergic function is associated with release of calcitonin gene-related peptide and substance P from trigeminal nerves, and may lead to vasodilation of cranial vessels and sensitization of meningeal afferents of the trigeminal nerve [5]. Estrogen may also affect other chemical mediators, such as nitric oxide, magnesium, or prostaglandins, which may also modulate the balance between excitatory and inhibitory neurotransmission [4,6].