Discussion
This systematic review included 36 trials for both acute and preventive treatments for menstrual migraine. Articles were further subdivided by category of treatment, which included triptans (7 studies for acute and 8 for preventive), combined therapy (2 studies for acute and 2 for preventive), prostaglandin synthesis inhibitor (1 study for acute), ergot alkaloid (1 study for acute), oral contraceptive (3 studies for preventive), estrogen (1 study for preventive), NSAID (1 study for preventive), phytoestrogens (2 studies for preventive), vitamin (1 study for preventive), GnRH agonist (2 studies for preventive), dopamine agonist (1 for preventive), mineral (1 for preventive), and nonpharmacological treatment (2 for preventive). Studies were selected by an extensive search across 4 different databases.
A decision was made to include open label studies and evidence with overall low quality in the final analysis to be both complete, and to include all data available for different treatment categories. A lot of the treatments used in common practice for preventive care of menstrual migraine lack strong supporting evidence for their use. A noticeable observation is that most of the evidence discovered for preventive treatment of menstrual migraine is of overall low quality, which was also reported in a prior evidence-based review by Pringsheim et al.
Triptans had the strongest evidence for both preventative and abortive menstrual migraine therapy, with randomized, placebo controlled trials for the most part. Hu et al published a systematic review of triptans in prevention of menstrual migraine with a meta-analysis in 2013 that included 6 RCTs with the result that frovatriptan and zolmitriptan are the preferred treatment regimens, which is consistent with our findings. Our data analysis showed that frovatriptan is superior to almotriptan and placebo for acute treatment of menstrual migraine with statistically significant results. Frovatriptan is superior to placebo in menstrual migraine prevention. For other triptans, which included naratriptan, sumatriptan, and zolmitriptan for acute treatment, all were superior to placebo. Triptans in prevention of menstrual migraine included frovatriptan, eletriptan, zolmitriptan, naratriptan, and sumatriptan. Frovatritan, naratriptan, and zolmitriptan were all superior to placebo in prevention of menstrual migraine. Studies for prevention with sumatriptan and eletriptan were open label only but both studies showed significant headache reduction. Pringsheim et al published an evidence based review that made recommendation B (based on US Preventive Task Force) for sumatriptan and rizatriptan for acute treatment based on the strength of evidence, which is consistent with our findings. Evidence for other triptans in acute treatment is not as strong. Triptans combined with either dexamethasone (RCT) or dexketoprofen (open label trial) showed significant pain relief. For combination of frovatriptan with combined oral contraceptive (RCT) or transdermal estrogen and naproxen (open label trial), there is an overall decrease in pain with combination therapy.
Other acute treatments discovered in analysis were mefenamic acid and dihydroergotamine. Mefenamic acid was superior to placebo in an RCT. A previous guideline made recommendation B for mefenamic acid for acute treatment based on the publication.
Oral contraceptives are commonly used in prevention of menstrual migraine with the idea to prevent fluctuation in estrogen levels, which may lead to migraine. Only 3 studies met our criteria for final inclusion in this review. All 3 studies are open label, prospective trials and show improvement in outcomes. Given the common use of contraceptives in menstrual migraine prevention, this is an area that requires further research.
For other preventative therapies for menstrual migraine, there is limited evidence. Most studies conducted were open label with small sample size, making evidence weak. Notable exceptions include placebo controlled trials for naproxen, nimesulide, estradiol gel, magnesium, vitamin E, and needling. All of these studies showed improvement of outcomes in the treatment groups with the exception of needling, where no significant differences were found between groups. Phytoestrogens, GnRH agonist, dopamine agonist, LUNA showed improvement in outcomes but all studies had a small sample size and were not blinded, which increases bias. In Pringsheim et al's evidence based review, nimesulide, magnesium, phytoestrogens, and naproxen were given recommendation I given the evidence is of poor quality.