Understanding the Causes and Prevention of Menstrual Migraine: The Role of Estrogen

Menstruation increases the risk of migraine in susceptible women. In a subpopulation of women with menstrual migraine, headaches occurring in association with onset of menses may be more severe and of longer duration than headaches experienced by the same woman at other times of her menstrual cycle. Although menstrual migraines share many clinical characteristics of other types of migraines, their occurrence is predictable provided that the patient has regular menstrual cycles. Therefore, short-term prevention regimens can be considered for women whose headaches are not adequately managed with acute therapies.     

Tailoring Management Strategies for the Patient With Menstrual Migraine: Focus on Prevention and Treatment

Many women report an increased frequency of headaches around the time of menses. For some women, these headaches are more severe, of longer duration, and lead to greater disability than those occurring at other times in the menstrual cycle. A headache diary is critical to properly diagnose menstrual migraine (MM) by prospectively documenting headache days, severity of headache, and the headaches' relationship to menses. In women with diagnosed MM, acute treatment has been proven to be effective in randomized clinical trials. For those women who have predictable periods and may require preventive therapy, short-term prevention is a reasonable approach due to the predictability of MM. Although several agents (eg, naproxen sodium, magnesium, triptans) have been evaluated for prevention of MM, all but triptans have been assessed in small trials of between 20 and 35 women. Naratriptan, frovatriptan, and, most recently, zolmitriptan have been proven effective in preventing MM. Triptans are generally well tolerated, and the long-term safety of these agents is currently being evaluated. The flexibility of using acute and preventive therapy allows physicians to tailor treatment of MM and meet the needs of individual patients.     

Reversible Hemiparesis in a Patient With Migraine

ABSTRACT

A third of patients with migraine may experience accompanying aura, and when this includes motor weakness, the condition is described as hemiplegic migraine. Young women who suffer from migraine with aura have a 6.2-fold increased risk of ischemic stroke. The slow progression and succession of symptoms help to provide the diagnosis of hemiplegic migraine.

This report is adapted from paineurope 2014; Issue 1, ©Haymarket Medical Publications Ltd., and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, Ltd., and is distributed free of charge to health care professionals in Europe. Archival issues can be accessed via the Web site: http://www.paineurope.com at which European health professionals can register online to receive copies of the quarterly publication.     

Scheduled Short-Term Prevention With Frovatriptan for Migraine Occurring Exclusively in Association With Menstruation

Objective.— This post hoc subgroup analysis evaluated scheduled short‐term preventive frovatriptan therapy for women with migraine occurring exclusively in association with menstruation (occurring day ?2 to +3; day 1 = menses start, no migraines outside this window). Background.— A previously published randomized, double‐blind, placebo‐controlled 3‐way crossover trial assessed the efficacy and safety of a scheduled 6‐day preventive regimen with frovatriptan for the treatment of menstrual migraine; the study population included women experiencing both menstrual and non‐menstrual migraine and women experiencing only menstrual migraine. Methods.— Women received each treatment (placebo, frovatriptan 2.5 mg once daily, and frovatriptan 2.5 mg twice daily) once over 3 perimenstrual periods in randomized sequence. For this subset analysis, screening questions were used to identify women with migraine occurring exclusively in association with menstruation. Efficacy was evaluated by occurrence and severity of migraine, functional impairment, and rescue medication use. Adverse events and tolerability were also assessed. Results.— Among 179 patients, the mean age (SD) was 37.3 (7.7) years and mean menstrual migraine history was 10.6 (8.7) years. Significantly fewer women experienced menstrual migraine during treatment with frovatriptan twice daily (37.7%, P < .001) or once daily (51.3%, P = .002) than during treatment with placebo (67.1%); a significant dose response was noted (P = .01, twice daily vs once daily). Significant treatment differences were also found for several secondary endpoints, but the data from this post hoc analysis must be interpreted with caution. Frovatriptan was well tolerated and most adverse events were mild or moderate and similar to those reported with the acute treatment of migraine with frovatriptan; the most common adverse events were nausea, dizziness, and headache. Conclusions.— Scheduled short‐term preventive frovatriptan therapy effectively reduced the occurrence of menstrual migraine in women with attacks occurring exclusively in association with menstruation.     

Factors associated with triptan use in episodic migraine: results from the American Migraine Prevalence and Prevention Study

Background.— Though triptans are considered the standard of acute therapy for migraine attacks with headache‐related disability, they are used by the minority of potentially eligible persons. Understanding the socio‐demographic and headache features that predict triptan use may help to clarify barriers to optimal treatment. Objective.— To assess the sociodemographic and headache features associated with triptan use in a US population sample of persons with episodic migraine. Methods.— The American Migraine Prevalence and Prevention Study (AMPP) is a longitudinal study conducted in a representative sample of US headache sufferers. Episodic migraineurs (n = 11,388) who provided treatment data in 2005 were included in the current analyses. We assessed factors associated with triptan use through univariate and multivariate analyses. Multivariate analyses were adjusted for sociodemographic factors, headache‐related disability, cutaneous allodynia, depression, and preventive headache medication use. Results.— Among persons with episodic migraine, 18.31% reported current use of triptans for acute headache treatment. In univariate analyses, triptan use was most common in midlife (ages 30‐59), among females, and was more common in Caucasians than in African Americans. Triptan use increased with headache frequency, headache‐related disability and allodynia, but decreased among persons with depression. In multivariate analyses, female gender, Caucasian race, age 40‐49, higher levels of education (college or higher), annual household income of ≥$40,000, having health insurance, the presence of cutaneous allodynia, greater headache‐related disability, and preventive medication use for migraine were significantly associated with triptan use. Conclusions.— Less than 1 in 5 persons with migraine in the United States who were respondents to this survey used triptans for acute headache treatment over the course of a year. Several markers of severe headache, including disability and allodynia, were associated with increased triptan use. Groups less likely to get triptans included males, African Americans, older adults, and the uninsured. Predictors of use provide insight into groups with unmet treatment needs.     

The Relationship of Ovarian Steroids, Headache Activity and Menstrual Distress: A Pilot Study With Female Migraineurs

Fourteen female volunteers who met diagnostic criteria for migraine headache monitored their headache activity and menstrual distress symptoms for one menstrual cycle. Serum estradiol and progesterone levels, and menstrual distress measures were collected at four points of the menstrual cycle: menstrual, ovulatory, luteal and premenstrual. Results indicated that one patient (7.1%) had menstrual migraine, 10 patients (71.4%) had menstrually-related headache and 3 (21.4%) had migraine headache unrelated to their menstrual cycle: subsequent analyses were conducted with the first two groups. Headache activity for the sample was highest during the premenstrual phase. Headache activity during the luteal and premenstrual phases was related to luteal phase progesterone levels. Menstrual distress was highest during the menstrual and premenstrual phases of the cycle, and these symptoms were related to higher estradiol levels, higher estradiol/progesterone ratios, and increased headache activity. These results indicated that for women with menstrual migraine or menstrually-related migraine, luteal progesterone and estradiol and the estradiol/progesterone ratio may be significantly related to menstrual distress during the premenstrual phase of the cycle. The estradiol/progesterone ratio was not more related to headache or menstrual distress than either of these ovarian hormones alone. Suggestions for future research in this area are offered.     

Butalbital and Pediatric Headache: Stay off the Downward Path

Despite limited evidence from the literature surrounding safety or efficacy, butalbital‐containing medicines (BCMs) have maintained their rank as “go‐to” prescribed migraine and headache relief drugs in the United States, despite bans on these barbiturates in Germany and other European countries. Providers at the Pediatric Headache Program at Boston Children's Hospital recommend that clinicians prescribe triptan‐based medications instead of BCMs, given the known negative side effects of BCMs on the general population, and the uncertain longitudinal trajectory of BCMs on developing brains.     

Menstrual Migraine: Pathophysiology, Diagnosis, and Impact

The incidence of migraine varies over the course of the menstrual cycle. In the general population, approximately 60% of women with migraine report an increased frequency of headache during menses. The estrogen withdrawal that occurs just prior to the onset of menses and that leads to loss of serotonergic tone is thought to be the trigger for headaches that arise at this time of the menstrual cycle. The ability of triptans, specific serotonin receptor agonists, to prevent menstrual migraine is consistent with this hypothesis. Moreover, compared with headaches that occur during other times in the cycle, menstrual migraines are more severe in most women and may be of longer duration, as well as more resistant to treatment in a subset of women.     

Lasmiditan Is a New Option for Acute Migraine Treatment

Lasmiditan is a new oral medication for treatment of acute migraine. It was approved by the U.S. Food and Drug Administration in October 2019 and is marketed under the brand name Reyvow (Eli Lilly and Company, Indianapolis, IN). It is the first of its kind in a new drug class called ditans. Lasmiditan has been studied as monotherapy for acute migraine treatment and as an abortive therapy for adults taking chronic migraine preventive medication. Lasmiditan may be an option for individuals who have had no relief with triptans or other acute migraine treatment agents or who are unable to use other migraine treatments because of contraindications.