Can estradiol (estrogen) worsen migraines?

From the Guidelines

Estradiol can worsen migraines in some individuals, particularly when hormone levels fluctuate. Many women experience more frequent or severe migraines during times of hormonal changes such as menstruation, when estrogen levels drop rapidly. This relationship is so established that there's a specific diagnosis called "menstrual migraine" for headaches that predictably occur around menstruation. Estrogen-containing medications like birth control pills or hormone replacement therapy can trigger or worsen migraines in susceptible individuals, as noted in guidelines for managing women with premature ovarian insufficiency 1. For those with migraine with aura, estrogen-containing contraceptives may even be contraindicated due to increased stroke risk. The mechanism involves estrogen's effects on blood vessels, neurotransmitters (particularly serotonin), and inflammation pathways in the brain. If you suspect estrogen is triggering your migraines, tracking your headaches in relation to your menstrual cycle or hormone medication use can help identify patterns. Some patients benefit from continuous hormone therapy to avoid fluctuations, while others do better avoiding hormonal medications altogether, as suggested by studies on hormone therapy for migraine prevention 1. Discussing these patterns with your healthcare provider can help determine the best approach for your specific situation. Key considerations include:

• The potential for estradiol to exacerbate migraines, especially in individuals with a history of menstrual migraine
• The importance of monitoring headache patterns in relation to hormonal changes or medication use
• The need for personalized treatment approaches, which may involve continuous hormone therapy, avoidance of hormonal medications, or alternative preventive strategies.

From the FDA Drug Label

1. Fluid retention Because estrogens may cause some degree of fluid retention, patients with conditions that might be influenced by this factor, such as asthma, epilepsy, migraine, and cardiac or renal dysfunction, warrant careful observation when estrogens are prescribed. 9 Exacerbation of other conditions Estrogens may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine or porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions.

Estradiol and Migraine: Estradiol may worsen migraines due to its potential to cause fluid retention and exacerbate conditions such as migraine.

• Patients with migraine should be carefully observed when taking estradiol.
• Estradiol should be used with caution in women with a history of migraine 2.

From the Research

Estradiol and Migraine

• Estradiol, a form of estrogen, has been linked to migraine attacks in various studies 3, 4, 5, 6, 7.
• The exact mechanisms by which estradiol affects migraine are not fully understood, but it is believed that fluctuations in estrogen levels can trigger migraine attacks 3, 4, 6, 7.
• Some studies suggest that a fall in plasma estradiol levels can trigger attacks of migraine without aura, while higher estradiol levels may be protective 7.
• Hormonal replacement therapy with estrogen, including estradiol, can exacerbate migraine in some women, particularly those with a history of menstrual migraine 5, 6.

Estradiol Fluctuations and Migraine

• Estradiol fluctuations during the menstrual cycle, menopause, and pregnancy can contribute to migraine attacks 4, 6, 7.
• The perimenopausal years, characterized by fluctuating and falling estrogen levels, may increase the frequency and severity of migraine in some women 6.
• Continuous combined hormone replacement therapy with estrogen and progesterone may be beneficial for women with migraine, as it can help stabilize estrogen levels and reduce migraine frequency 6.

Treatment Considerations

• Hormonal treatment of migraine is not a first-line treatment strategy for most women with migraine, and evidence regarding its long-term safety and efficacy is limited 4.
• The use of exogenous estrogen, including estradiol, is contraindicated in women with aura and those aged 35 or older due to the increased risk of stroke and other cardiovascular events 4.