Treatment of Menstrual Migraines
For women with menstrual migraines, start with optimized acute treatment using triptans (particularly rizatriptan or sumatriptan) or NSAIDs, and if this fails to provide adequate control, initiate perimenstrual preventive treatment with a long-acting NSAID or triptan for 5 days, beginning 2 days before the expected first day of menstruation. 1
Initial Assessment
Any woman of reproductive age presenting with migraine must be asked about the relationship between her attacks and menstruation 1. Approximately 50% of women with migraine experience increased attacks during their menstrual period, though only about 8% have attacks exclusively related to menstruation 1. These attacks are typically more severe, longer lasting, and more resistant to treatment than non-menstrual migraines 2, 3.
Acute Treatment Strategy
First-Line Acute Options
NSAIDs are the initial acute treatment choice, with the strongest evidence supporting acetylsalicylic acid, ibuprofen, and diclofenac potassium 4. Naproxen or naproxen sodium shows modest but statistically significant effects on headache frequency 4. Mefenamic acid 500 mg also has demonstrated efficacy 3.
Second-Line Acute Options
When NSAIDs provide inadequate relief, triptans should be offered 4. Among triptans, rizatriptan has the best overall evidence for acute treatment of menstrual migraine, with pain-free responses of 33-73% at 2 hours and sustained pain relief of 63% between 2-24 hours 2. Sumatriptan 50-100 mg and rizatriptan 10 mg both show similar efficacies of 61-63% for 2-hour pain freedom 2, 3.
Triptans must be taken early in the attack when headache is still mild 4. They should not be used during the aura phase 4. The combination of sumatriptan/naproxen 85 mg/500 mg has evidence of efficacy with acceptable safety 3.
Perimenstrual Preventive Treatment
When to Initiate Prevention
If optimized acute medication therapy does not suffice, perimenstrual preventive treatment should be initiated 1. This approach is appropriate for women whose attacks can be predicted through patient diaries recording headache onset and relationship to the menstrual cycle through three complete cycles 5.
Preventive Medication Protocol
The standard protocol is a long-acting NSAID or triptan for 5 days, beginning 2 days before the expected first day of menstruation 1.
Triptan Options for Prevention
- Frovatriptan 2.5 mg twice daily has grade B evidence of efficacy and the most extensive research for short-term prevention, with four randomized controlled trials demonstrating statistically significant results 3, 6
- Naratriptan 1 mg twice daily has grade B evidence with two studies showing efficacy 3
- Zolmitriptan three times daily has one trial demonstrating effectiveness 2
NSAID Options for Prevention
Naproxen sodium has statistically significant results for short-term prevention 2, 3. NSAIDs have demonstrated effectiveness in menstrual migraine prophylaxis 7.
Hormonal Approaches
Transcutaneous estradiol 1.5 mg has grade B evidence of efficacy for perimenstrual prophylaxis 3. Two placebo-controlled trials of estradiol administered premenstrually as a gel or patch suggest that relatively high dosage (1.5 mg per day of the gel form) may be effective in women whose migraines are associated with their menstrual cycle 4. However, evidence does not support benefit in patients whose migraines are not menstruation-related 4.
Special Considerations
Pregnancy and Breastfeeding
Paracetamol should be used as first-line medication during pregnancy despite relatively poor efficacy 4. NSAIDs can only be used during the second trimester 4. For breastfeeding women, paracetamol is preferred, though ibuprofen and sumatriptan are considered safe 4.
NSAID Safety
NSAIDs can cause ulcers and bleeding in the stomach and intestines at any time during treatment, which can happen without warning symptoms and may cause death 8. The risk increases with longer use, smoking, drinking alcohol, older age, and concurrent use of corticosteroids or anticoagulants 8. NSAIDs should be used at the lowest dose possible for the shortest time needed 8.
Contraceptive Considerations
Combined oral contraceptives containing drospirenone, taken continuously for 168 days, have shown promising results 7. Many antiepileptic medications used for migraine prevention can affect the efficacy of oral contraceptives, so caution is indicated when these are combined 2. Topiramate has the least effect on oral contraceptives at doses below 200 mg/day 2.
Alternative Therapies
Magnesium has shown benefits over placebo in two studies for prevention 4, 2. High-dose vitamin B2 (riboflavin 400 mg) showed significant benefit at three and four months after initiation 4. Phytoestrogens and ginkgolide B have some evidence of efficacy 7.