Ovarian Hormones and Migraine Headache: Understanding Mechanisms and Pathogenesis--Part 2

Vincent T. Martin, MD; Michael Behbehani, PhD


Headache. 2006;46(3):365-386. 

In This Article

Reproductive Life Events And Hormonal Therapies

Reproductive life events as well as hormonal therapies can be preventative or provocative for migraine depending on the "hormonal milieu" to which the patient is exposed. A decline of serum estradiol levels of the magnitude experienced prior to menstruation (eg, decline from 250 to 300 pg/mL to 25 to 50 pg/mL) is clearly provocative for patients with menstrual migraine. It is unknown if a similar "magnitude" of decline at higher serum levels would be provocative for migraine. More stable levels of estrogen (eg, serum levels maintained within a 45 to 75 pg/mL range) as administered in the form of a 100-mcg transdermal estradiol patch are preventative for migraine in some postmenopausal women. A complete remission of attacks of MWoA can be induced during the third trimester of pregnancy with serum estradiol levels ranging from 13,000 to 15,000 pg/mL and progesterone levels ranging from 150 to 200 ng/mL.[79] Therefore, different hormonal milieus can have vastly different effects on the clinical course of migraine ( Table 4 ).

Reproductive life events affect MWA differently than MWoA ( Table 4 ). The onset of MWoA occurs after the development of menarche suggesting that the development of the female menstrual cycle could play a role in its initiation, while MWA generally begins prior to menarche or at least prior to development of consistent menstrual cycles. Falling estradiol levels at the time of menstruation seem to trigger attacks of MWoA, but not attacks of MWA. MWoA tends to improve with pregnancy, but patients with pure MWA may not.[79,87] The prevalence of migraine increases during the perimenopausal time period in patients experiencing MWoA, but remains unchanged in those with MWA. Therefore, patients with MWoA seem to be more responsive to the effects of changing ovarian hormones. Interestingly, symptoms of premenstrual syndrome and menopause (eg, hot flashes) have also been reported in some studies to be more common in patients with MWoA.[12,87]

There may be different subgroups of migraineurs that are more sensitive to the changes in hormones encountered with reproductive events. For example, women with migraine onset during menarche are more likely to have improvement in their migraines during pregnancy, while those with menstrual migraine are less likely to improve during the first and third trimesters of pregnancy.[9,79] Women who experience hot flashes during the perimenopause or those with a history of premenstrual syndrome may be more likely to experience migraine during the perimenopause.[12,95] Therefore, a history of menstrual migraine, premenstrual syndrome, hot flashes, or onset of migraine during menarche may signify that a given patient is "hormonally sensitive" and thus more likely to be affected, either positively or negatively, by other hormonal events.


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