Pharmacological treatment plays a key role in managing period migraines by targeting both the symptoms during an attack and preventing future episodes.

The three types of treatment strategies include:

• Acute treatment: enhanced to hit these migraines harder than usual migraines
• Mini-prevention: is a preventive treatment given before and during the menstrual window
• Long-term prevention: in which a daily preventive treatment is used throughout the month.

The choice of treatment depends on the individual's symptoms, frequency of migraines, and response to previous therapies. A personalized approach, often guided by a healthcare professional, helps ensure that the chosen medication strategy is both effective and well-tolerated.

Warning:
Pharmacological treatment option is always recommended under a doctor's supervision. Consult your doctor before taking any of the medications mentioned below.

NSAIDs

What Are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

Non-steroidal anti-inflammatory drugs (NSAIDs) are medicines that are widely used to relieve pain, reduce inflammation, and bring down a high temperature.

NSAIDs are available as tablets, capsules, suppositories (capsules inserted into the bottom), creams, gels, and injections. Some can be bought over the counter from pharmacies, while others need a prescription.

The main types of NSAIDs include:

• Ibuprofen
• Naproxen
• Diclofenac
• Mefenamic acid
• Etoricoxib
• Indomethacin
• Aspirin¹

How Do NSAIDs Work?

Cyclooxygenase (COX) is the enzyme that mediates the bioconversion of arachidonic acid to inflammatory prostaglandins (PGs).

NSAIDs are competitive inhibitors of COX, thus decreasing the production of prostaglandins, which results in decreased pain.¹

What Is the Efficacy of NSAIDs for Period Migraines?

Methods: Multiple high-quality studies, including a systematic review and network meta-analysis, were conducted to evaluate the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in the acute treatment of migraines, including menstrual migraines. These studies involved adult participants with diagnosed migraine, including those with menstrual migraine patterns, and compared NSAID efficacy both alone and in combination therapies.²³⁴

Results: NSAIDs such as ibuprofen and naproxen showed significant benefit over placebo in achieving 2-hour pain relief and pain freedom. A fixed-dose combination of aspirin, paracetamol, and caffeine significantly improved headache relief and patient satisfaction compared to placebo.

Conclusion: NSAIDs, particularly ibuprofen and diclofenac-potassium, are effective, well-tolerated treatments for managing acute menstrual migraines. Combination therapies, such as aspirin with paracetamol and caffeine, further enhance efficacy and patient satisfaction. These findings support NSAIDs as a viable first-line option for individuals seeking relief from period-related migraine attacks.

What Are the Side Effects of NSAIDs?

• Short-term effects: Nausea, diarrhea
• Long-term effects: Myocardial Infarction, thromboembolic events, and atrial fibrillation¹

Triptans

What Are Triptans?

Triptans, also known as serotonin receptor agonists, are a class of drugs used to treat acute attacks of migraines. They are available in different formulations and include:

• Sumatriptan
• Naratriptan
• Zolmitriptan
• Rizatriptan
• Almotriptam
• Frovatriptan
• Eletriptan

How Do Triptans Work?

Triptans work by binding to serotonin receptors in the brain, called 5-HT1B and 5-HT1D. When you have a migraine, the blood vessels in your head become swollen and enlarged. When triptans attach to 5-HT1B receptors on blood vessels in the brain, they cause these vessels to narrow, which reduces the pain.

When triptans attach to the neurogenic and central 5-HT1D receptors, they prevent the release of certain protein-like molecules known as vasoactive neuropeptides by inhibiting trigeminal nerve activation and blocking the transmission of pain signals to the central nervous system.⁵

What Is the Efficacy of Triptans for Period Migraines?

Method: Several studies were conducted to assess the effectiveness of triptans in treating menstrual migraine. Both acute treatment and short-term prevention were evaluated.⁶⁷⁸

Results: Triptans like sumatriptan, rizatriptan, zolmitriptan, and almotriptan provided rapid relief from menstrual migraines. Many women achieved pain-free status within 2 hours, with sustained relief up to 24 hours. Frovatriptan 2.5 mg twice daily, taken for about 5–6 days around menstruation, significantly reduced the frequency, severity, and recurrence of menstrual migraines.

Conclusion: Based on the studies, triptans are effective and well-tolerated treatments for menstrual migraines. As acute therapy, they provide fast and effective relief from migraine attacks, and as short-term prevention, especially with frovatriptan, they help prevent migraines when taken in the days around menstruation.

What Are the Side Effects of Triptans?

• Short-term effects: Nausea, dizziness, tingling
• Long-term effects: Coronary vasoconstriction, paresthesia, arrhythmias, myocardial infarctions, and strokes⁵

Combined Oral Contraceptives

What Are Combined Oral Contraceptives?

Combination birth control pills, also known as the pill, are oral contraceptives that contain estrogen and a progestin.

Combination birth control pills come in different mixtures of active and inactive pills, including:

Conventional pack: One common type contains 21 active pills and seven inactive pills. Inactive pills do not contain hormones. Formulations containing 24 active pills and four inactive pills, known as a shortened pill-free interval, are also available. Some newer pills may contain only two inactive pills.

You take a pill every day and start a new pack when you finish the old one. Packs usually contain 28 days of pills. Bleeding may occur every month during the time when you take the inactive pills that are at the end of each pack.

Extended-cycle pack: These packs typically contain 84 active pills and seven inactive pills. Bleeding generally occurs only four times a year during the seven days you take the inactive pills.

Continuous-dosing pack: A 365-day pill is also available. You take this pill every day at the same time. For some people, periods stop altogether. For others, periods become significantly lighter. You do not take any inactive pills.⁹

How Do Combined Oral Contraceptives Work?

Menstrual migraine occurs due to a decrease in the level of estrogen during the menstrual cycle, particularly 2 days before and 3 days after the period. Combined Oral Contraceptives prevent these drops of estrogen by providing consistent level of estrogen and therefore reduces the intensity and frequency of the attacks.¹⁰

What Is the Efficacy of Combined Oral Contraceptives for Period Migraines?

Method: A prospective randomized study was done to compare the efficacy of two regimens (21 active pills + 7 placebo pills vs. 24 active pills + 4 placebo pills) of combined oral contraception (COC), both containing 20 μg of ethinyl E2 and 3 mg of drospirenone, in improving the severity of pure menstrual migraine without aura.

Results: Although both study groups demonstrated significant reduction in the intensity and duration of menstrual migraine, patients in group B (24/4 COC) reported a significant reduction in the intensity and a shorter duration of their menstrual migraine, compared with group A (21/7 COC).

Conclusion: The 24/4 COC regimen is recommended as the preferred treatment for patients suffering from pure menstrual migraine without aura.¹¹

What Are the Side Effects of Combined Oral Contraceptives?

• Short-term effects: Breast tenderness, nausea, headaches, bloating, and unscheduled bleeding
• Long-term effects: Increased risk of venous and arterial thromboembolism (deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke), mild increase in blood pressure, and possible increases in breast and cervical cancer risk¹²

References

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2. Diener HC, Gaul C, Lehmacher W, Weiser T. Aspirin, paracetamol (acetaminophen) and caffeine for the treatment of acute migraine attacks: A systemic review and meta-analysis of randomized placebo-controlled trials. European Journal of Neurology. 2022 Jan;29(1):350-7.

3. Xu H, Han W, Wang J, Li M. Network meta-analysis of migraine disorder treatment by NSAIDs and triptans. The Journal of Headache and Pain. 2016 Dec;17(1):113.

4. VanderPluym JH, Singh RB, Urtecho M, et al. Acute treatments for episodic migraine in adults: a systematic review and meta-analysis. JAMA. 2021 Jun 15;325(23):2357-69.

5. Nicolas S, Nicolas D. Triptans. StatPearls Publishing. 2024 Feb 25.

6. Zhang H, Qi JZ, Zhang ZH. Comparative efficacy of different treatments for menstrual migraine: a systematic review and network meta-analysis. The Journal of Headache and Pain. 2023 Jul 3;24(1):81.

7. Hu Y, Guan X, Fan L, Jin L. Triptans in prevention of menstrual migraine: a systematic review with meta-analysis. The Journal of Headache and Pain. 2013 Dec;14(1):7.

8. Khoo CC, Liu CC, Lu M, Huang YC, Weng HY. Acute and preventive treatment of menstrual migraine: a meta-analysis. The Journal of Headache and Pain. 2024 Sep 4;25(1):143.

9. Cooper DB, Patel P, Mahdy H. Oral contraceptive pills.

10. Nappi RE, Tiranini L, Sacco S, De Matteis E, De Icco R, Tassorelli C. Role of estrogens in menstrual migraine. Cells. 2022 Apr 15;11(8):1355.

11. De Leo V, Scolaro V, Musacchio MC, Di Sabatino A, Morgante G, Cianci A. Combined oral contraceptives in women with menstrual migraine without aura. Fertility and Sterility. 2011 Oct 1;96(4):917–920.

12. Edwards M, Can AS. Progestins. StatPearls. 2024 Jan 10.