What are the treatment options for a female patient of reproductive age with a history of migraines related to her menstrual cycle?

Treatment of Menstrual Migraine

For menstrual migraine, initiate acute treatment with NSAIDs (ibuprofen, naproxen, or diclofenac) taken early when headache is mild, and if inadequate, escalate to triptans; for women with predictable perimenstrual attacks, add short-term prophylaxis with frovatriptan 2.5 mg or naratriptan 1 mg twice daily starting 2 days before expected menstruation for 5 days, combined with naproxen 500 mg twice daily. 1, 2

Acute Treatment Approach

First-Line Acute Therapy

• NSAIDs are the initial acute treatment choice, with strongest evidence for acetylsalicylic acid, ibuprofen, and diclofenac potassium 2
• Naproxen or naproxen sodium shows modest but statistically significant effects on headache frequency 2
• These medications must be taken early in the attack when headache is still mild 2

Second-Line Acute Therapy

• Triptans should be offered when NSAIDs provide inadequate relief 2
• Rizatriptan has the best overall evidence for acute treatment, with pain-free responses of 33-73% at 2 hours and sustained pain relief of 63% between 2-24 hours 3
• Sumatriptan 50-100 mg shows 61-62% headache response at 2 hours, with no significant difference between these doses 4, 3
• All triptans must be taken early when headache is still mild 2

Critical Monitoring for Acute Treatment

• Limit acute treatments to <10 days/month for triptans and <15 days/month for NSAIDs to prevent medication overuse headache 1

Perimenstrual Short-Term Prophylaxis

When to Initiate

• Consider perimenstrual prophylaxis when optimized acute medication therapy does not suffice 2
• Requires prospective headache diary documentation for at least 3 menstrual cycles to confirm the menstrual relationship and predict timing 2, 5

Recommended Regimens

• Frovatriptan 2.5 mg twice daily OR naratriptan 1 mg twice daily, starting 2 days before expected menstruation and continuing for 5 days total 1, 2
• Combine with naproxen 500 mg twice daily during the same 5-day period 1
• Alternative: Zolmitriptan three times daily has shown statistically significant results 3

Hormonal Prophylaxis Option

• Transcutaneous estradiol 1.5 mg has grade B evidence for perimenstrual prophylaxis 2
• Important caveat: Evidence does not support benefit in patients whose migraines are not menstruation-related 2

Daily Preventive Treatment

When Daily Prevention is Needed

• When multiple attacks occur throughout the menstrual cycle, not just perimenstrually 2, 5
• When perimenstrual prophylaxis combined with acute treatment fails 1

First-Line Daily Preventive Options

• Propranolol 80-160 mg daily in long-acting formulations (if not contraindicated) 1
• Topiramate 50-100 mg daily reduces perimenstrual migraine frequency by approximately 46% 1

Second-Line Daily Preventive Options

• CGRP monoclonal antibodies: erenumab 70-140 mg subcutaneous monthly, or fremanezumab 225 mg monthly/675 mg quarterly 1
• OnabotulinumtoxinA 155-195 units to 31-39 sites every 12 weeks for chronic migraine in women who have failed first-line agents 1

Alternative Preventive Therapies

• Magnesium has shown benefits over placebo in prevention 2
• High-dose vitamin B2 (riboflavin 400 mg) showed significant benefit at 3-4 months after initiation 2

Critical Contraindications and Safety Warnings

Absolute Contraindications

• Sodium valproate is absolutely contraindicated in women of childbearing potential due to high rates of fetal anomalies 1, 6
• Topiramate is contraindicated in pregnancy due to teratogenic effects and requires effective contraception in women of childbearing potential 1

Relative Contraindications

• Combined hormonal contraceptives are contraindicated if the patient has migraine with aura due to increased stroke risk 1, 7
• This is particularly important when other risk factors such as smoking are present 7

Drug Interactions

• Many antiepileptic medications used in migraine prevention can affect the efficacy of oral contraceptives and hormonal treatments 3
• Topiramate has the least effect on oral contraceptives at doses below 200 mg/day 3

Special Population Considerations

Pregnancy

• Paracetamol is first-line medication during pregnancy, despite relatively poor efficacy 2
• NSAIDs can only be used during the second trimester 2

Breastfeeding

• Paracetamol is preferred 2
• Ibuprofen and sumatriptan are considered safe 2

Monitoring and Follow-Up Strategy

• Evaluate treatment response at 2-3 months using headache calendars to track attack frequency, severity, and disability 1
• Monitor for medication overuse as specified above 1
• Maintain prospective menstrual and headache diaries for at least 3 cycles before initiating perimenstrual prophylaxis 2, 5

Common Pitfalls to Avoid

• Do not initiate perimenstrual prophylaxis without documented menstrual relationship over at least 3 cycles 2, 5
• Do not delay triptan administration—efficacy depends on early treatment when headache is mild 2
• Do not use combined hormonal contraceptives in women with migraine with aura 1, 7
• Do not prescribe valproate to any woman of childbearing potential 1, 6
• Do not overlook medication overuse headache risk with frequent acute treatment 1