Clinical Recommendations for Managing Menstrual Migraine (2025)

Published: January 9, 2025|Vera Gibb

Menstrual migraine (MM) affects 20–25% of women with migraine and accounts for 22–70% of patients in specialized headache centers.1 For a healthcare provider, migraine attacks that occur around a person’s menstrual cycle can be the most challenging and difficult to treat.2 We will review the diagnosis of menstrual migraine, examine its underlying mechanisms, and outline both the acute and preventive treatment strategies commonly utilized.

Diagnosis

According to the International Classification of Headache Disorders, menstrual migraine (MM) is separated into two subtypes:

  • Pure menstrual migraine is a migraine attack occurring exclusively on day 1 ± 2 of menstruation in at least two out of three menstrual cycles and at no other time in the cycle.3
  • Menstrually-related migraine is defined as above but may occur at other times in the menstrual cycle not only around menstruation.4

Menstrual migraine attacks typically occur without aura.2 These attacks often last longer, are more severe, and can be more resistant to treatment, likely due to the effects of ovarian hormones, especially estrogen.2

Underlying Mechanisms

Research has identified two primary pathophysiological mechanisms for menstrual migraine: estrogen withdrawal and prostaglandin release.5 The estrogen withdrawal hypothesis suggests that a drop in estrogen levels during the premenstrual phase triggers migraine attacks by modulating pain within the trigeminovascular system.6 The most targeted treatment approach for menstrual migraine involves hormone manipulation to stabilize estrogen levels and reduce migraine frequency and severity.5

Clinical Recommendations for Managing Menstrual Migraine (1)

This slide is shared with the permission of the American Headache Society.

Treatment

Currently, there are no FDA-approved treatments specifically for Menstrual Migraine.

Menstrual Migraine treatment is divided into:

  1. Acute: Used at the onset for each migraine attack
  2. Short-term prevention: Continuous use of acute treatments, which may put patients a risk of medication overuse headache, especially in those with unpredictable menstrual cycles
  3. Continuous prevention

Acute Treatments

Oral Pharmacological Options

Triptans shown to be effective for the acute treatment of menstrual migraine include sumatriptan, frovatriptan, naratriptan, zolmitriptan, and almotriptan.5 While all these triptans provide superior pain relief compared to placebo within 2–4 hours, not all demonstrate significantly better results than placebo in preventing migraine recurrence within 24 hours post-dose.5

For enhanced efficacy, consider adding an shorter-acting NSAID (e.g., ibuprofen, diclofenac) or a longer-acting NSAID (e.g., naproxen, nabumetone) with a triptan at the onset of the attack.

  • Sumatriptan plus naproxen has been shown to be efficacious in clinical trials.5

Rimegepant (75 mg PO), ubrogepant (50 or 100 mg PO), and zavegepant (10 mg nasal spray) are CGRP receptor antagonists that may be effective treatments for menstrual migraine. Hormonal fluctuations during menstruation are associated with an increase in calcitonin gene-related peptide (CGRP), a key neurotransmitter involved in migraine pathophysiology.7 By targeting CGRP, these medications may help to reduce the frequency and intensity of menstrual migraine.

Lasmiditan, a 5-HT1F receptor agonist, can also be an effective treatment for menstrual migraine.8 It does not cause vasoconstriction and could be an alternative to a triptan. However, it is classified as a Schedule V controlled substance and includes a warning to avoid driving or operating heavy machinery for 8 hours after use.8

Non-oral medications

As with any migraine attack, some patients may prefer non-oral medications for faster onset of action, but they may be especially useful for those who experience vomiting during attacks, which could impair the absorption of oral medications.

  • Triptans may be prescribed as an injectable (sumatriptan 4 mg or 6 mg) or as a nasal spray (sumatriptan 5 mg, 10 mg or 20 mg or zolmitriptan 2.5 mg or 5 mg).
  • Dihydroergotamine nasal spray may be used for harder-to-treat attacks.

Neuromodulation Devices

Neuromodulation devices are considered a safe and effective non-pharmaceutical option. The devices can be used as an adjunct to medications or as a standalone treatment.

  • Theranica’s remote electrical neuromodulation (REN) device, Nerivio, is an FDA-cleared, smartphone-controlled prescription device designed for the acute and preventive treatment of migraine. As an acute treatment, it can be used during a migraine attack, and as a preventive option, it can be worn every other day.
    • In a clinical study of 91 women aged 18 to 55 with menstrual migraine (MM), each participant used the device for at least 4 treatment sessions.9 The results showed that 74.7% (n = 68) reported the treatment as at least moderately effective. The device offers a non-pharmacological alternative for patients seeking acute relief or preventive strategies.9

Short-Term Prevention

Short term prevention should be initiated in those with predictable menstrual cycles. In those who have irregular cycles, treatment can be ineffective and can contribute to medication overuse headache.

Triptans

  • Frovatriptan 2.5 mg may be administered twice daily, starting two days prior to the onset of menses and continuing throughout the menstruation.10 Its extended half-life has been demonstrated to reduce both the severity and duration of migraine, as well as the need for additional acute medication.10
  • Naratriptan 1 mg PO twice daily for 6 days per month is an effective and well-tolerated preventive option for short-term prevention of menstrually-related migraine in people with regular menstrual cycles.11 Unlike frovatriptan, many insurance plans will cover naratriptan without a prior authorization or sumatriptan failure.11

NSAIDS

  • NSAIDs, such as ibuprofen and naproxen, work by inhibiting the release of prostaglandins—compounds that increase significantly at the start of menstruation and play a role in causing pain during menstruation.12 By blocking the enzyme cyclooxygenase (COX), NSAIDs reduce the production of these prostaglandins, which can alleviate uterine contractions and reduce the pain and discomfort associated with menstrual cramps and headache.12
  • 550 mg of naproxen taken twice a day for 5-7 days around the start of a period can reduce the number of headache days as well as the severity and duration of attacks.13

Gepants

  • Some clinicians may prescribe rimegepant 75 mg PO every other day as a short-term preventive strategy prior to the onset of menstruation.

Estrogen supplementation

  • The estrogen gel or patch may be used in the peri-menstrual period to prevent the estrogen drop in people with predictable menstrual cycles.5
  • An oral contraceptive containing 20 μg ethinyl estradiol on days 1 to 21, supplemented with 0.9 mg conjugated equine estrogens on days 22 to 28 may be used to prevent menstrual migraine.5
  • Estrogen is best supplemented during the estrogen-free interval of oral contraceptives, especially in people taking low-dose oral contraceptives.5

Supplements

  • In a small clinical trial, oral magnesium (360 mg) taken daily from day 15 of the menstrual cycle until the next menses has been shown to be an effective mini-prophylactic strategy. This approach may be particularly beneficial for patients with irregular menstrual cycles.
  • A double-blind, placebo-controlled trial found that taking 400 IU of vitamin E daily for 5 days (from 2 days before menses to 3 days after) significantly reduced pain intensity and disability while also providing greater relief from associated symptoms such as photophobia, phonophobia, and nausea compared to placebo.5,14

Acupuncture

  • A randomized controlled trial found that three cycles of acupuncture as a preventive treatment for MM significantly reduced the number of migraine days for six cycles compared to the naproxen treatment.15 However, the use of acute pain medication did not differ between the two groups.15

Continuous Prevention

For those with irregular periods or when short-term prevention is ineffective, using preventive medications may be the most effective strategy for managing menstrual migraine. Options include CGRP monoclonal antibodies, gepants, and non-migraine-specific medications such as antidepressants, anti-epileptic drugs, antihypertensives and more.

Providers should be aware that many anti-epileptic drugs used for migraine prevention can reduce the effectiveness of oral contraceptives and hormonal treatments. Therefore, caution is advised.

  • Topiramate has the least effect on oral contraceptives at doses below 200 mg/day.2 However, due to risk of fetal abnormalities, this medication is contraindicated in other countries for people of childbearing age who are not using highly effective contraception.16
  • Lamotrigine can decrease oral contraceptive levels.2

Hormonal therapies

While MM has traditionally been managed with abortive and prophylactic treatments, such as non-steroidal anti-inflammatory drugs (NSAIDs) and triptans, recent evidence suggests that these can be used in combination with specific hormonal therapies.

For patients with migraine without aura, recommended hormonal treatments include:

  • Continuous combined hormonal contraceptives without placebo pills may help prevent menstrual migraines by stabilizing estrogen levels and minimizing fluctuations
  • Limiting placebo pills to two days to reduce the estrogen withdrawal trigger
  • Non-oral formulations, such as the vaginal ring

It’s important to note that prescribing estrogen-containing oral contraceptives for individuals with migraine with aura is highly controversial. Individual risk factors for stroke, heart disease, and blood clots must be assessed before prescribing all contraceptives. Progesterone-only implants or oral contraceptives are typically considered safer than estrogen-containing oral contraceptives for people with migraine with aura or migraine without aura.17

Conclusion

Overall, many new and effective pharmacological and non-pharmacological treatments are now available to help those living with menstrual migraine. By combining migraine and hormonal therapies and adding supplements and neuromodulation devices, we can decrease the burden of menstrual migraine by achieving better migraine control, resulting in better overall patient outcomes and quality of life.

Resources

References

  1. Vetvik KG, MacGregor EA. Menstrual migraine: a distinct disorder needing greater recognition. Lancet Neurol. 2021 Apr;20(4):304-315. doi: 10.1016/S1474-4422(20)30482-8. Epub 2021 Feb 15. PMID: 33600767.
  2. Maasumi K, Tepper SJ, Kriegler JS. Menstrual Migraine and Treatment Options: Review. Headache. 2017 Feb;57(2):194-208. doi: 10.1111/head.12978. Epub 2016 Dec 2. PMID: 27910087.
  3. https://ichd-3.org/appendix/a1-migraine/a1-1-migraine-without-aura/a1-1-1-pure-menstrual-migraine-without-aura/
  4. https://ichd-3.org/appendix/a1-migraine/a1-1-migraine-without-aura/a1-1-2-menstrually-related-migraine-without-aura/
  5. Ornello, R., De Matteis, E., Di Felice, C., Caponnetto, V., Pistoia, F., & Sacco, S. (2021). Acute and Preventive Management of Migraine during Menstruation and Menopause. Journal of clinical medicine, 10(11), 2263. https://doi.org/10.3390/jcm10112263
  6. Raffaelli, B., Do, T. P., Chaudhry, B. A., Ashina, M., Amin, F. M., & Ashina, H. (2023). Menstrual migraine is caused by estrogen withdrawal: revisiting the evidence. The journal of headache and pain, 24(1), 131. https://doi.org/10.1186/s10194-023-01664-4
  7. Raffaelli B, Storch E, Overeem LH, Terhart M, Fitzek MP, Lange KS, Reuter U. Sex Hormones and Calcitonin Gene-Related Peptide in Women With Migraine: A Cross-sectional, Matched Cohort Study. Neurology. 2023 Apr 25;100(17):e1825-e1835. doi: 10.1212/WNL.0000000000207114. Epub 2023 Feb 22. PMID: 36813730; PMCID: PMC10136010.
  8. Khoo CC-W, Liu C-C, Lu M, Huang Y-C, Weng H-Y. Acute and preventive treatment of menstrual migraine: a meta-analysis. J Headache Pain. Published online September 4, 2024. doi:10.1186/s10194-024-01848-6
  9. Nierenburg H, Rabany L, Lin T, et al. Remote electrical neuromodulation (REN) for the acute treatment of menstrual migraine: a retrospective survey study of effectiveness and tolerability. Pain Ther. Published online June 17, 2021. doi: 10.1007/s40122-021-00276-7
  10. Silberstein SD, Elkind AH, Schreiber C, Keywood C. A randomized trial of frovatriptan for the intermittent prevention of menstrual migraine. Neurology. 2004 Jul 27;63(2):261-9. doi: 10.1212/01.wnl.0000134620.30129.d6. PMID: 15277618.
  11. Mannix LK, Savani N, Landy S, Valade D, Shackelford S, Ames MH, Jones MW. Efficacy and tolerability of naratriptan for short-term prevention of menstrually related migraine: data from two randomized, double-blind, placebo-controlled studies. Headache. 2007 Jul-Aug;47(7):1037-49. doi: 10.1111/j.1526-4610.2007.00855.x. PMID: 17635595.
  12. https://www.acog.org/womens-health/faqs/dysmenorrhea-painful-periods#:~:text=Prostaglandins%20cause%20the%20muscles%20and,few%20days%20of%20a%20period
  13. Sances G, Martignoni E, Fioroni L, Blandini F, Facchinetti F, Nappi G. Naproxen sodium in menstrual migraine prophylaxis: a double-blind placebo controlled study. Headache. 1990 Nov;30(11):705-9. doi: 10.1111/j.1526-4610.1990.hed3011705.x. PMID: 2074162.
  14. https://medscimonit.com/abstract/index/idArt/869523
  15. Liu L, Zhang CS, Liu HL, He F, Lyu TL, Zeng L, Zhao LP, Wang MN, Qu ZY, Nie LM, Guo J, Zhang XZ, Lu YH, Wang KL, Li B, Jing XH, Wang LP. Acupuncture for menstruation-related migraine prophylaxis: A multicenter randomized controlled trial. Front Neurosci. 2022 Aug 26;16:992577. doi: 10.3389/fnins.2022.992577. PMID: 36090267; PMCID: PMC9459087.
  16. https://www.hpra.ie/docs/default-source/default-document-library/important-safety-information-topamax-(topiramate).pdf?sfvrsn=0
  17. Nappi RE, Merki-Feld GS, Terreno E, Pellegrinelli A, Viana M. Hormonal contraception in women with migraine: is progestogen-only contraception a better choice? J Headache Pain. 2013 Aug 1;14(1):66. doi: 10.1186/1129-2377-14-66. PMID: 24456509; PMCID: PMC3735427.

Author

Clinical Recommendations for Managing Menstrual Migraine (2)

Vera Gibb, DNP, APRN, FNP-C, AQH, CCTP is a Family Nurse Practitioner in primary care and an Assistant Professor, Graduate Studies Department, School of Nursing, of The University of Texas Medical Branch (UTMB) at Galveston. She holds additional certifications in headache medicine, clinical trauma, and interprofessional education. Vera Gibb serves on the Board of Directors of Coalition for Headache and Migraine Patients (CHAMP) and the Advisory Board of The First Contact – Headache in Primary Care Program of the American Headache Society. She’s actively involved in improving headache education for current and future providers across different healthcare disciplines.

Clinical Recommendations for Managing Menstrual Migraine (2025)
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