Women with Migraine: Options for Decreasing Disability

Abstract & Commentary

By Dara Jamieson, MD

Synopsis: Menstrually related migraine is difficult to treat and options are limited. Hormonal manipulation is controversial and unproven.

Sources: Cady RK, et al. Sumatriptan-naproxen sodium for menstrual migraine and dysmenorrhea: Satisfaction, productivity, and functional disability outcomes. Headache 2011;51:664-673. Allais G, et al. Perimenstrual migraines and their response to preventive therapy with topiramate. Cephalalgia 2011;31:152-160. Nappi RE, et al. Effects of an estrogen-free, desogestrel-containing oral contraceptive in women with migraine with aura: A prospective diary-based pilot study. Contraception 2011;83:223-228.

Treatment of menstrually related migraine (mrm) is especially challenging. For women with MRM, the head pain may be just one component of their monthly disability. A sumatriptan/naproxen sodium combination tablet was used to treat MRM associated with dysmenorrhea during the mild headache pain phase. In two multicenter, randomized, double-blind, placebo-controlled trials, women with menstrual migraine and dysmenorrhea treated a single menstrual migraine attack with a single fixed-dose tablet of sumatriptan 85 mg and naproxen sodium 500 mg or placebo. Participants randomized to sumatriptan-naproxen sodium were significantly more satisfied with the treatment than those randomized to placebo at 24 hours post-dose, as demonstrated by higher satisfaction subscale scores for efficacy, functionality, and ease of use. Use of sumatriptan-naproxen sodium for treatment of MRM and dysmenorrhea also was associated with lower reported "lost-time equivalents" in work and leisure time, and lower rates of functional disability compared with placebo.

Preventive treatment with topiramate is effective for overall reduction of migraine frequency, but data from premenopausal women as a subgroup of the Prolonged Migraine Prevention with Topiramate (PROMPT) study were analyzed to determine whether topiramate can specifically prevent MRM. After a 1- to 2-month prospective baseline period, 198 women with MRM received open-label topiramate (50-200 mg/day) for 6 months. During topiramate treatment, mean monthly migraine frequency was reduced from 7.03 at baseline to 4.36 (mean change: -2.66; P < 0.001, endpoint analysis). Mean percentage reductions were similar for migraines during and outside the perimenstrual period (-45.9% and -46.1%, respectively). In women with migraine with aura (MWA), reductions in migraine days with or without aura were similar to those in women without aura. Reductions in days of headache also were not affected by the use of combined oral contraceptives (COCs). Topiramate treatment did not affect migraine duration and there was only minor reduction in severity of the headache. Topiramate reduces the frequency, but not severity or duration, of perimenstrual migraines in women with MRM, including migraines with and without aura and without regard to COC use.

MWA is associated with an increased risk of ischemic stroke and to a lesser extent coronary artery disease, and the use of COCs is often avoided, especially in women with MWA and other vascular risk factors of hypertension and smoking. Women who have migraine without aura may develop auras with the use of COCs. The progestogen-only contraceptive pill (POP) appears to be a safe alternative to COCs in these women. In a prospective diary-based pilot study, 30 women with MWA (half were COC naive) were followed for 9 months. After a 3-month run-in period, each subject received an estrogen-free desogestrel (DSG) (75 mcg/day)-containing OC. Follow-up evaluations were planned at the end of the third and sixth month of treatment. The number (mean + SD) of migraine attacks was significantly reduced both in previous COCs users (from 3.9 + 1.0 to 2.9 + 0.8; P < 0.001) and nonusers (from 3.2 + 0.9 to 2.6 + 1.3; P < 0.02) following 6 months of POP use, in comparison with the run-in period. Duration of headache pain did not differ significantly between both groups throughout the study. A beneficial POP effect on the duration of visual aura (from 16.3 + 9.5 to 11.4 + 5.6 min) and on the total duration of neurological symptoms (from 33.6 + 23.3 to 18.6 + 18.0 min) was only significant in previous COC users at the end of the study period. There was a trend toward decreased analgesic use and vomiting associated with the POP. The POP was well-tolerated by women in both groups and breakthrough bleeding was infrequent.

Commentary

The majority of the approximately 30 million American migraine sufferers are women and about 20% of all women are at least periodically disabled by migraines. The most problematic migraines for women are menstrual migraines, which tend to be more severe than episodic migraine, and MWA, which are physically debilitating and concerning because of their association with increased vascular risk. Strategies to treat migraine in women combine lifestyle modifications and medications, both acute and preventive, with hormonal manipulation to decrease the impact of falling estrogen or estrogen withdrawal in triggering headaches. These papers offer options to treat women with migraine headaches. Both placebo-controlled studies of the efficacy of sumatriptan/naproxen sodium combination tablet and topiramate in patients with MRM refine our knowledge of these medications. Although positive results compared to no treatment are not unexpected, MRM headaches last longer, are more disabling, and are less responsive to treatment than other migraines. More information is needed from head-to-head comparison of different acute and preventive treatments to decrease the time spent trying various treatment strategies for women with migraine.

Contraception in women with active MWA is problematic, since the vascular risk of pregnancy exceeds the vascular risk of the combination of MWA and COCs, and since stroke in women who have MWA is generally associated with a good functional outcome. Menstrual suppression with COCs is an option to decrease MRM for some women, but this option is generally limited to women who do not have active MWA. The POP seems to offer decreased vascular risk with slightly decreased pregnancy protection, although its use may not be satisfactory to some women as compared to the benefits of COCs.