Menstrual migraines: Which options and when?

Possible mechanisms of MRM and PMM. The etiology of migraine is not well understood and is likely multifactorial.⁴ Incidence of menstrual migraines is related to cyclic changes in female hormones—specifically, the decreasing levels of estrogen that typically happen the week before onset of menses.¹ The mechanism is not yet clear, though it is thought that a decline in estrogen levels triggers a decline in serotonin levels, which may lead to cranial vasodilation and sensitization of the trigeminal nerve.^5,6 Estrogen decline has also been linked to increased cranial nociception as well as decreased endogenous opioid activity. A study using positron emission tomography found increased activity of serotonergic neurons in migraineurs.⁷ The evidence that triptans and serotonin receptor agonists are effective in the treatment of migraine also supports the theory that serotonin neurohormonal signaling pathways play a critical role in the pathogenesis of migraines.⁷

Prevalence patterns point to the role of estrogen. The prevalence of migraines in women increases around puberty, peaks between ages 30 and 40, and decreases after natural menopause.⁶ Migraine prevalence increases during the first week postpartum, when levels of estrogen and progesterone decrease suddenly and significantly.¹ Migraine frequency and intensity decrease in the second and third trimesters of pregnancy and after menopause, when estrogen levels fluctuate significantly less.¹ In the Women’s Health Initiative study, women who used hormone replacement therapy (HRT) had a 42% increased risk of migraines compared with women in the study who had never used HRT.⁸

Migraines related to menses typically last longer, are more severe, less likely to be associated with aura, and more likely to be recalcitrant to treatment than non-menstrual migraines.The association of migraine with female hormones was further supported by a Dutch study of male-to-female transgender patients on estrogen therapy, who had a 26% incidence of migraine, equivalent to the 25% prevalence in natal female controls in this study, compared with just 7.5% in male controls.⁹ The association between migraine and estrogen withdrawal was investigated in studies performed more than 40 years ago, when women experiencing migraines around the time of menses were given intramuscular estradiol and experienced a delay in symptom onset.¹⁰