Menstrual Migraine

Menstrual migraine is migraine without aura (rarely with aura) occurring in relation to menstruation, where attacks occur on day 1 plus or minus 2 days (from 2 days before to 3 days after the onset of menstrual bleeding) in at least two of three consecutive cycles. Attacks are triggered by the fall in oestradiol before menstruation and tend to be longer, more severe, more disabling and more resistant to treatment than non-menstrual attacks.

• Pure menstrual migraine: attacks occur only in this window and at no other time in the cycle (about 3 to 7 percent of women with migraine).
• Menstrually related migraine: attacks occur in this window but also at other times of the cycle (about 35 to 50 percent of women with migraine).
• Pathophysiology: withdrawal of oestradiol in the late luteal phase, with prostaglandin release, in susceptible women; often improves in pregnancy, on the contraceptive pill with a hormone free interval removed, and after menopause.
• Menstrual attacks are more likely to recur within 24 hours after initial relief.

• Migraine without aura clustered around menstruation: severe, throbbing headache with nausea, vomiting, photophobia and phonophobia, lasting up to 3 days, with early recurrence.
• Usually associated with premenstrual symptoms (mood, breast tenderness, bloating), heavy menstrual bleeding or dysmenorrhoea.
• Between menstrual attacks the patient may be free of headache (pure form) or have other attacks.
• Pelvic and abdominal examination if menstrual abnormality, dysmenorrhoea or heavy bleeding.
• Aura, if it occurs, usually does not occur in menstrual attacks.

• Prospective headache and menstrual diary over at least 3 cycles, recording the start of each period, headache days, severity, duration and medication use.
• Exclude pregnancy before starting therapy if the cycle is irregular.
• Investigations when indicated: blood pressure; haemoglobin and ferritin (heavy bleeding); TSH; prolactin; pelvic ultrasound for suspected endometriosis, fibroids or heavy menstrual bleeding.
• Review contraceptive method and hormone use, and assess vascular risk factors (smoking, hypertension, obesity, family history of early cardiovascular disease, age).
• Differentials: other primary headaches coincidental with menses, medication overuse headache, hormonal contraceptive related headache in the pill free interval, iron deficiency, endometriosis associated headache, idiopathic intracranial hypertension.

Acute treatment

• Dose early, at the first sign of headache: ibuprofen 400 to 600 mg or naproxen 500 to 750 mg orally with metoclopramide 10 mg; sumatriptan 50 to 100 mg orally (maximum 300 mg daily) or zolmitriptan 2.5 to 5 mg or rizatriptan 10 mg; combination sumatriptan 50 mg with naproxen 500 mg for recurrence. Repeat the triptan if headache returns after 2 hours.

Short term (perimenstrual) prevention for regular cycles (start 2 days before expected onset of headache)

• Frovatriptan 2.5 mg orally twice daily for 6 days (from 2 days before the expected attack through day 3 of menses; or 2.5 mg once daily).
• Naratriptan 1 mg orally twice daily for 5 days.
• Zolmitriptan 2.5 mg orally twice daily or three times daily for 5 to 6 days.
• Naproxen 500 mg orally twice daily with food for 5 to 7 days, starting 2 days before expected menses.
• Mefenamic acid 500 mg orally three times daily with food, from the first day of menses (or first sign of headache) until the end of the headache window, for up to 5 days; helpful with dysmenorrhoea and heavy bleeding.
• Triptan use is limited to under 10 days a month overall.

Hormonal prevention

• Transdermal oestradiol 100 micrograms patch (or oestradiol gel 1.5 mg daily) applied from 3 days before expected menstruation for 7 days, in women with regular cycles and with no aura and no contraindication to oestrogen. Withdraw oestrogen if aura develops.
• Combined oral contraceptive taken continuously (omitting the hormone free interval) or extended regimen (21 days active followed by a shortened break of 4 days or less), only if migraine is without aura and vascular risk factors are absent. Contraindicated in migraine with aura (stroke risk), and with smoking over age 35, hypertension, obesity with other risk factors, history of venous thromboembolism, or breast cancer.
• Progestogen only methods avoiding fluctuation: desogestrel 75 micrograms daily continuously, etonogestrel implant, or levonorgestrel intrauterine system 52 mg (these are safe in migraine with aura).
• Gonadotropin releasing hormone analogues with add back therapy, or tamoxifen, in specialist care for refractory cases.

Daily preventive treatment

• For attacks not confined to menses: propranolol, amitriptyline, topiramate (with effective non-hormonal contraception), candesartan 8 to 16 mg daily, or anti-CGRP antibodies (erenumab 70 to 140 mg subcutaneously monthly or galcanezumab 240 mg loading then 120 mg monthly).

Associated measures

• Treat heavy menstrual bleeding with tranexamic acid 1 g orally three times daily for up to 4 days, or levonorgestrel intrauterine system; correct iron deficiency with ferrous sulfate 200 mg twice daily or ferrous fumarate; regular sleep, exercise and stress management.

Follow up

• Review after 3 cycles; continue diary; step up to daily prevention if short term prevention fails or if attacks occur outside the menstrual window.

Special groups

• Pregnancy: menstrual migraine usually improves; avoid triptan prevention and oestradiol; use paracetamol and metoclopramide.
• Breastfeeding: avoid oestrogen containing methods in the first 6 weeks; sumatriptan is compatible.
• Perimenopause: attacks may worsen with fluctuating oestradiol; continuous combined or oestradiol patch with progestogen, if no aura and no contraindication.