What treatment should be considered for a woman experiencing premenstrual migraines, nausea, fatigue, and brain fog around day 24 of her menstrual cycle for 3-4 days?

Treatment of Premenstrual Migraines with Associated Symptoms

For this 47-year-old woman with predictable premenstrual migraines occurring around day 24 of her cycle, perimenstrual prophylaxis with naproxen 500-550mg twice daily starting 2 days before expected symptoms (day 22) and continuing for 5 days is the most appropriate first-line approach, with frovatriptan 2.5mg twice daily as an alternative if NSAIDs are contraindicated or ineffective. 1

Rationale for Perimenstrual Prophylaxis

• The predictable timing of symptoms around day 24 (2-4 days before expected menstruation) makes this patient an ideal candidate for short-term preventive therapy rather than relying solely on acute treatment 1
• The American Academy of Neurology specifically recommends perimenstrual preventive treatment with a long-acting NSAID (like naproxen) or triptan (like frovatriptan or naratriptan) for 5 days, beginning 2 days before expected menstruation, when acute treatment alone is insufficient 1
• This approach targets the estrogen withdrawal that predictably precipitates menstrual migraine, addressing the underlying trigger rather than just treating symptoms 2, 3

Specific Treatment Protocol

First-Line: Naproxen Perimenstrual Prophylaxis

• Start naproxen 500-550mg twice daily on day 22 of her cycle (2 days before symptom onset) and continue through day 27 1, 4
• This regimen addresses not only the migraine but also the associated nausea and fatigue through anti-inflammatory mechanisms 2
• Naproxen's long half-life provides sustained coverage throughout the vulnerable perimenstrual window 1

Alternative: Frovatriptan Perimenstrual Prophylaxis

• If naproxen is contraindicated (renal impairment, GI bleeding history) or ineffective after 2-3 cycles, switch to frovatriptan 2.5mg twice daily for the same 5-day perimenstrual window 1, 5
• Frovatriptan has the best evidence among triptans for short-term prevention, with four randomized controlled trials demonstrating statistically significant results 5
• Naratriptan 1mg twice daily is another long-acting triptan option with proven efficacy for perimenstrual prophylaxis 1

Acute Breakthrough Treatment

• Despite perimenstrual prophylaxis, breakthrough migraines may still occur and require acute treatment 2
• For breakthrough attacks, use rizatriptan 10mg or sumatriptan 50-100mg at headache onset, as these have the strongest evidence for acute menstrual migraine treatment with pain-free responses of 61-73% at 2 hours 1, 5
• Add metoclopramide 10mg orally 20-30 minutes before the triptan to address nausea and enhance triptan absorption through prokinetic effects 6, 1

Critical Frequency Monitoring

• Strictly limit all acute migraine medications to no more than 2 days per week to prevent medication-overuse headache 6, 1
• If the patient requires acute treatment more than twice weekly despite perimenstrual prophylaxis, transition to daily preventive therapy with propranolol 80-240mg daily or topiramate 6, 1
• Use a headache calendar to track attack frequency, severity, and medication use to objectively assess treatment response 1

Hormonal Considerations

• Continuous combined hormonal contraceptives (skipping placebo pills) can reduce hormone fluctuations and benefit women with pure menstrual migraine without aura 1, 3
• However, combined hormonal contraceptives are absolutely contraindicated if this patient has any history of migraine with aura due to increased stroke risk 1, 3
• Transcutaneous estradiol 1.5mg daily (gel or patch) applied perimenstrually has grade B evidence as an alternative hormonal approach 1

Treatment Evaluation Timeline

• Assess treatment response after 2-3 menstrual cycles 1
• If one preventive strategy fails, try another drug class as failure of one does not predict failure of others 1
• Consider the Migraine Treatment Optimization Questionnaire (mTOQ-4) to objectively evaluate effectiveness 1

Critical Pitfalls to Avoid

• Do not use opioids or barbiturates for menstrual migraine due to dependency risk, rebound headaches, and poor efficacy 1
• Do not allow the patient to increase frequency of acute medication use beyond twice weekly, as this creates medication-overuse headache and worsens the underlying problem 6, 1
• Do not prescribe triptans during aura phase if present—they are ineffective and should only be used when headache begins 1
• Ensure the patient understands that perimenstrual prophylaxis requires daily dosing during the 5-day window regardless of whether symptoms appear, as the goal is prevention rather than acute treatment 1, 4