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

Vincent T. Martin, MD; Michael Behbehani, PhD

Disclosures

Headache. 2006;46(3):365-386. 

In This Article

Estrogen And Migraine

Estrogen in particular appears to modulate the frequency, severity, and disability of migraine headache. The effects of estrogen appear to be strongly influenced by the specific levels of serum estradiol levels. A decline in estrogen levels during the perimenstrual time period will trigger menstrual migraine, but only when serum levels fall below a threshold of 45 to 50 pg/mL. Sustained moderate-to-high serum estradiol levels such as these experienced with pregnancy and HRT seem to be preventative for some patients with MWoA. High serum levels of estrogen such as those experienced with pregnancy and HRT or high potency estrogens (eg, OCPs) may worsen MWA in some patients. Thus moderate-to-high levels of serum estradiol seem to be preventative for some patients with MWoA while provocative for others with MWA.

How sensitive might some migraineurs be to changes in serum estradiol levels? The above mentioned medical oophorectomy study[109] found that headache outcome measures were 45–50% higher during the first 2 days after application of a transdermal estradiol patch when compared to the fifth and sixth days after a patch change while no differences were seen between patch days in the placebo group. Within the estradiol treated group, serum estradiol levels were maintained in a very narrow range varying from 50 pg/mL during the first 2 patch days to 42 pg/mL during the last 2 days of the patch. Therefore, despite an "overall" preventative effect with the transdermal estradiol patch compared with placebo, a small rise (eg, 11 pg/mL) in serum estradiol levels on the first 2 days of the patch might be provocative for migraine headache. These results emphasize how exquisitely sensitive some migraineurs may be to small changes in serum estradiol levels and demonstrate that estrogen can be preventative in some situations and provocative in others.

The above data also suggest that migraine with and without aura are triggered by different mechanisms. Attacks of MWoA are triggered by declines in serum estradiol, while attacks of MWA are triggered by sustained high levels of estradiol. The mechanisms through which estrogen triggers these two subtypes of migraine are largely speculative. One might hypothesize that moderate-to-high serum levels of estrogen trigger attacks of MWA through enhancement of cortical glutamatergic neurotransmission or development of platelet microemboli, which could then trigger attacks on a vascular or ischemic basis. In regard to MWoA, declining levels of estradiol might trigger migraine through effects on excitatory and inhibitory neurotransmission within trigeminal pain pathways.

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