Menstrual Migraine and Treatment Options: Review

Abstract

Objective: A review of treatment options for menstrual migraine.

Background: Migraine affects ∼30 million people in the US. A subset of female migraineurs have migraines that are mainly associated with menstruation. Menstrual migraine (MM) is divided into pure MM and menstrually related migraine. Pure MM attacks occur only with menstruation and have a prevalence of 1%. Menstrually related migraine has a prevalence of 6-7%, and occurs both during menstruation as well as during the rest of the cycle. MM is usually without aura and is more severe, longer lasting, and more resistant to treatment due to the effects of ovarian hormones, specifically estrogen. MM treatment is divided into acute, short-term prophylaxis, and daily prevention. The best-studied acute treatments are triptans. For short-term prophylaxis, triptans, non-triptans, or combinations are used. Some preventive medications may be used daily to prevent MM. Many anti-epileptic medications used in migraine prevention can affect the efficacy of oral contraceptives and hormonal treatments, so caution is indicated when these are used.

Methods: PubMed, Scopus, Cochrane, and Embase were searched for MM and treatments.

Results: Many randomized, placebo-controlled, prospective studies have evaluated the efficacy of sumatriptan, rizatriptan, naratriptan, zolmitriptan, and almotriptan in MM. Reviewing numerous studies with statistically significant results, rizatriptan has the best overall evidence for acute treatment of MM, ranging from pain-free responses of 33-73% at 2 hours. Sumatriptan and rizatriptan have shown similar efficacies of 61-63% in terms of 2 hour pain freedom. Rizatriptan showed sustained pain relief between 2 and 24 hours with an efficacy of 63% and sustained pain freedom for MM between 2 and 24 hours with an efficacy of 32%. For short-term prevention of MM, there were four randomized controlled trials for frovatriptan taken twice daily, one trial for zolmitriptan taken three times daily, and two studies for naratriptan taken twice daily, all of which showed statistically significant results. Among studies on non-triptans for short-term prevention of MM, magnesium, estrogen, naproxen sodium, and dihydroergotamine all had statistically significant results. Many antiepileptic medications taken for prevention of MM can cause enzyme induction affecting oral contraceptives (OCs) and hormonal treatments to different degrees. Topiramate has the least effect on OCs at doses below 200 mg/day. Lamotrigine noticeably decreases oral contraceptive levels; however, the evidence for it as a preventive medication is not strong.

Conclusion: MM can be very difficult to treat. For acute treatments, rizatriptan has the best overall evidence. For short-term prevention, frovatriptan, zolmitriptan, or naratriptan, as well as magnesium, estrogen, naproxen sodium, or dihydroergotamine may be useful.

Keywords: estrogen; hormones; menstrual migraine; menstrually related migraine; prophylaxis.