In 2021 Dr. Lars Edvinsson’s team published a beautiful review on the hormonal influences in migraine, which informs our understanding of menstrual migraine (1). First, I will present the treatment implications and steps you can take to potentially improve your migraine care today. Second, I will present the science for those of you who are interested in understanding the ‘why’ behind menstrual migraine.
Treatment Implications
Developing a mensural migraine-specific treatment plan may help you better manage your migraine. Menstrual migraine attacks can be particularly difficult to treat and they typically last longer than non-menstrual associated attacks, which suggests that a different treatment approach may be required.
Things to look out for – First, take note of when your attacks arise relative to your menstrual cycle stage (on/off period). Second, observe how effective your medications/treatments are during these attacks. Menstrual migraine attacks can be particularly difficult to treat and medications may be less effective during this stage of your cycle.
If you experience migraine attacks around your menstrual cycle, you could try…
- GEPANTs during your cycle: In a randomized trial, women took a GEPANT for 7 consecutive days around the time of menstruation for 6 months. In this study, menstrual-related attack were reduced, indicating a preventive effect of this drug and consumption pattern (2).
- Longer acting triptans: Speaking of a menstrual-migraine specific treatment plan, one option is to try longer lasting triptans since menstrual migraine attacks often last longer than non-menstrual attacks. Frovatriptain is the longest lasting triptan, but research also supports the efficacy of naratriptan, sumatriptan and zolmitriptan (3, 4).
- Magnesium supplementation. Daily oral magnesium supplementation can reduce the frequency of migraine attacks by over 40%, and it seems to be particularly effective in preventing menstrual related migraine (5, 6). Read about the types of magnesium supplements here.
- Aerobic exercise: Individuals who completed 40 minutes of aerobic exercise at least three times a week had a reduction in the frequency of their migraine attacks equal to those who used the drug Topamax.(topiramate) (7).
- Continuous contraceptive or hormone replacement strategies: These options provide an additional option for management (8), although clinical trial data are limited and the side effects and long-term implications should be carefully considered by you and your treatment team.
The Science
The Evidence for Hormone Influence in Migraine
For *migraine without aura, attack prevalence increases during the menstrual period and scientists are still trying to understand why. In rodents, estrogen receptors are expressed all throughout the brain regions involved in migraine (hypothalamus, thalamus, brainstem, amygdala, cortex, etc.).
If you have any kind of background in endocrinology, you might be asking, what about progesterone? Well, studies have demonstrated that progesterone isn’t a key player. In fact, data suggest that migraine attacks are specifically triggered by estrogen withdraw but not progesterone withdraw.
Furthermore, we also know that estrogen prevents *CGRP release.This suggests that when estrogen drops to its lowest levels during menses that CGRP release increases, which likely contributes to the menstrual period-associated attacks.
Finally, estrogen also promotes oxytocin release, a hormone known to have anti-nociceptive (pain relieving) effect and intranasal administration of oxytocin actually suppressed migraine attacks.
Thus, the current theory is that withdrawal of estrogen during the mensural cycle contributes to increased migraine attack prevalence through its interaction with CGRP and oxytocin, among other neurocomponents.
Footnotes:
*1. Note that these data focus on migraine WITHOUT aura. In migraine with aura, the highest risk of attack in women is seen during high levels of estrogen (e.g. during pregnancy) suggesting a unique mechanisms for this subtype of migraine. Also important to remember that familial hemiplegic migraine type 1 is considered a type of migraine with aura.
*2. Calcitonin gene-related peptide (CGRP) is a small protein that is migraine-inducing and is the target of the new classes of migraine-specific medications, CGRP monoclonal antibodies and GEPANTS.
References
- https://www.nature.com/articles/s41582-021-00544-2
- https://journals.sagepub.com/doi/abs/10.1177/0333102415584308
- https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1007/s10194-012-0455-4
- https://journals.sagepub.com/doi/abs/10.1111/j.1468-2982.2009.01840.x
- https://pubmed.ncbi.nlm.nih.gov/8792038/
- https://americanmigrainefoundation.org/resource-library/magnesium/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236524/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002599/
Life With Migraine 