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


The World Health Organization has defined the perimenopause as the time period 2 to 8 years prior to menopause as well as the year after cessation of menses.[92,93] Women experience variable lengths of their menstrual cycles, heavier menstrual bleeding, anovulation, and intermittent amenorrhea during this time. Levels of ovarian hormones during native menstrual cycles may differ between perimenopausal and younger women. Santoro et al[94] found that the urinary estrogen metabolites were higher and progesterone metabolites were lower throughout the menstrual cycle in perimenopausal than younger women (Figure 5). Such a "hormonal milieu" might be provocative for migraine during the perimenopausal time period if higher levels or greater fluctuations in estrogen provoke migraine. If mid-luteal progesterone is preventative for migraine, then anovulation encountered during the perimenopause could be provocative for migraine.

Urinary estrogen and progesterone metabolites during natural menstrual cycles in perimenopausal and younger cycling women. Note that urinary estrogen metabolites are higher and progesterone metabolites are lower in perimenopausal women than in younger cycling women aged 19 to 38 (Graphs A and B, respectively). Day 1 is the first day of menstruation and day 28 is the last day before the next menstrual cycle. All urinary hormone values are divided by creatinine to correct for variations in concentrations within urine samples. (Reproduced with permission from Santoro N. J Clin Endocrinol Metab 1996;81:1495-1501.)

No longitudinal diary studies have been conducted to determine the exact effect of the perimenopausal time period on migraine headache. Two cross-sectional studies,[12,95] however, have suggested that the prevalence of migraine headache is higher during the perimenopausal transition than during early menopausal time periods. The increased prevalence of migraine, however, was only encountered in those with a past history of MWoA and premenstrual syndrome. Therefore, these two subgroups of migraineurs may be more prone to the hormonal effects of the perimenopause.


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