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

Mechanisms Of Ovarian Hormones

Ovarian hormones, whether encountered during menstrual cycles or with hormonal therapies, could modulate migraine headache through a number of mechanisms including the "rate of change,""magnitude of change,""hormonal burden," or a "threshold effect." The "rate of change" of ovarian hormones is calculated by determining the "slope of a rise or fall" in hormone levels around a hormonal peak. "Magnitude of change" is defined as the absolute difference between peak and trough hormone levels of a hormonal peak. The "hormonal burden" is calculated by measuring the area-under-the-curve of hormones during hormone peaks. There could also be a "threshold effect" of ovarian hormones, which refers to a level of serum hormones above or below which migraine may be triggered or prevented (Figure 6).

Theorized mechanisms through which ovarian hormones could modulate migraine headaches. (A) "Rate of change" is calculated by the slope of the rise or decline in serum hormone levels. (B) "Hormonal burden" is determined by measuring the area-under-the-curve of hormone peaks. (C) "Magnitude of change" signifies the absolute difference in peak and trough hormone levels. (D) The "threshold effect" indicates that a certain level of ovarian hormone exists above or below which migraine is triggered.

A recent study[16] did not find that "rates of change,""magnitude of change," or "total hormonal burden" of urinary estrogen metabolites influenced headache outcome measures during menstrual cycles in premenopausal female migraineurs. Higher "hormonal burdens" of urinary progesterone metabolites, however, were associated with worse headache outcome measures during mid-luteal time periods. This might appear to be contrary to the above mentioned hypothesis that progesterone could be preventative for migraine during the mid-luteal phase of the menstrual cycle, but could suggest that a threshold of serum progesterone levels exists above which migraine is provoked and below which it is prevented. There may also be a "threshold" of serum estradiol levels below which migraine might be triggered after a decline of estrogen. Sommerville[24] and Lichten[127] noted that menstrual migraine was triggered when serum levels of estradiol fell below 45 to 50 pg/mL during the perimenstrual time period. Therefore, preliminary evidence would suggest that a "threshold effect" may be the most relevant mechanism through which ovarian hormones modulate migraine headache.


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