1. Screen for menstrual and menstrual-related migraine.

2. Choose contraceptive methods that reduce frequency of menstrual-related migraine.

3. Use triptans for acute treatment or as short-term prevention of migraine.

4. Discuss changes that occur during puberty that may contribute to migraine and other pain disorders.

5. Counsel pregnant women about nonpharmacologic and pharmacologic management of migraine.

Migraine: A Gynecologic Overview
Philip M. Wakefield, MD, Chief of Obstetrics and Gynecology, Eliza Coffee Memorial Hospital, Florence, AL

Introduction: migraine more common in women than in men; before puberty, incidence of migraine slightly higher in boys; in most women, incidence of migraine decreases during pregnancy, but may recur 3 to 6 days after delivery due to drop in estrogen; consider leak headache, preeclampsia, eclampsia, subarachnoid hemorrhage, or sinus thrombosis; be concerned about migraines that do not improve after menopause and migraines that begin after menopause; hormonal decreases may cause midcycle spotting and headache; migraines often influenced by prostaglandins associated with menstrual fluid (treated with, eg, sumatriptan, nonsteroidal agent)

Hormonal therapy: study found no occurrence of headache and no delay in onset of menses in women who received high doses of intramuscular (IM) estrogen (until estrogen levels dropped); continuous use of oral contraceptives (OCs) for 3 to 12 mo may lead to breakthrough bleeding; in some cases, treating with estrogen (eg, transdermal system [“patch”]; 0.1 mg/day) before menses may prevent headache; migraineurs have hyperexcitable brain (not absolute level of estrogen that predisposes women to migraines but relative drop in estrogen)

Screening: 46% of women with migraine have menstrual-related migraine; 14% have pure menstrual migraine; questions to ask—ask about clustering (eg, migraine begins 2-3 days before menses and lasts through first 2 days of menses); “do you have recurrent headaches?” “do your headaches interfere with your life?” “of your last 3 periods, how many times have you had headaches?” “is your period predictable?” ask patient to keep headache calendar; discuss premonitory symptoms and behaviors (eg, dizziness, elation, depression)

Treatment: acute therapy for infrequent migraines; short-term strategies for predictable headaches with long duration and poor response to acute therapy (long-term strategies for unpredictable headaches); acute therapy—triptans; ergot agents (not used by speaker); speaker not enthusiastic about butorphanol nasal spray (Stadol NS) due to risk for abuse; oral nonsteroidal anti-inflammatory drugs (NSAIDs) commonly used

Symptoms with OC withdrawal: headache; pelvic pain; breast tenderness; bloating; swelling; use of pain medications; consider continuous OCs

Counseling patients: encourage use of headache calendar; establish diagnosis; educate patients; establish realistic expectations (100% response to medications unlikely); create management plan with patient

OCs for continuous prevention: commonly used; lack of consensus; ethinyl estradiol and norethindrone (eg, Estrostep 21; tricyclic OC) changes estrogen levels as month progresses (other tricyclic agents affect progestin levels [may not be as effective]); speaker recommends against levonorgestrel-releasing intrauterine system (Mirena) due to difficulty of placement in nulliparous patient; copper intrauterine device (IUD) leads to more bleeding, inflammation, and prostaglandins; due to side effects, inducing menopause with hormone therapy last resort for refractory cases; if patient had severe preeclampsia at early stage (eg, 27-29 wk gestation), consider coagulation defects (factor V Leiden mutation present in 5% of population; not candidates for OCs due to higher risk for thromboembolic events); screen patients carefully; chance for stroke in 1 yr in OC users with migraine, 1 in 1300

Red flags: fever; weight loss; HIV; systemic cancer; confusion; impaired alertness or consciousness; sudden and abrupt onset of migraine; advanced age; first headache not migraine until proven; crashing headache with orgasm (refer to neurologist); crashing headache, fever, and premature rupture of membranes in pregnancy (consider disseminated herpes)

Menstrual Migraines
Lisa K. Mannix, MD, Medical Director, Headache Associates, Cincinnati, OH

Introduction: menstrual migraine and treatment not same for all women; many women feel headache normal part of menstruation; help patients identify migraine

Classification: proposed diagnostic criteria from International Headache Society (IHS) debatable; pure menstrual migraine—headaches occur only within menstrual window (eg, beginning ≈2 days before onset of menses and lasting for first 3 days of menses); menstrual-related migraine—headaches occur during menstrual window and other times of month; migraine without aura tends to peak during menstrual window; some women have migraine with aura; headaches must occur in ≥2 of 3 cycles

Treatment: headache diary; acute treatment—analgesics; NSAIDs; triptans appropriate as first-line treatment for moderate to severe migraine; long-term prophylaxis—for women who need daily preventive agent; short-term prophylaxis—for vulnerable times (eg, menses); menses must be predictable; hormonal treatment may be effective

Pure menstrual migraine: case presentation—woman 34 yr of age with history of headache since age 11 yr; misses work due to headache 2 days before each menses; menses regular; woman underwent tubal ligation for contraception; headache occurs during menstrual window; start acute treatment on day of headache onset; triptans— treat early and aggressively; if headache recurs, repeat treatment (eg, on second day); appear effective for acute treatment (rizatriptan and zolmitriptan appeared superior to placebo); consider early intervention

Menstrual-related migraine: case presentation—woman 41 yr of age with history of headache since college that gradually increased in frequency; comorbidities include anxiety and depression; headaches more severe during first 3 days of menses; woman has menstrual-related migraine (ie, severe menstrual migraine occurs during menstrual window with weekly occurrence of other migraines); conventional migraine-preventive therapy—tricyclic agents; antiepilepsy medications; antihypertensive agents; consider comorbidities (selective serotonin reuptake inhibitor [SSRI] or serotonin-norepinephrine reuptake inhibitor [SNRI] may be reasonable); for acute treatment, consider triptan and cognitive behavioral strategies; menstrual migraines may be easier to treat or identify by reducing overall burden of disease (ie, eliminating other migraines during month); consider long-term daily preventive strategies

Short-term prevention: case presentation—woman 23 yr of age; not sexually active; woman has dysmenorrhea and requires use of NSAID every month; triptans provide temporary relief for migraine; since menses predictable and patient does not need hormone therapy, short-term prevention can be started several days before onset of headache (refer to patient’s headache calendar); if headaches occur, woman can treat acutely (with, eg, triptans); short-term prevention options—magnesium; NSAIDs (on scheduled basis rather than as needed; eg, start naproxen 3-7 days before menses and continue through menstrual flow); supplemental estrogen (eg, transdermal system, ≥0.1 mg/day); estradiol gel—study found that when applied 6 days before menses, frequency, duration, and severity of migraine decreased; when estrogen gel removed, headaches spiked; individualize treatment; 7- day course appropriate for most women; breakthrough headaches can be treated with triptan

Triptans: case presentation—woman 37 yr of age on combination OCs; within 2 days of stopping active OC pills, migraine occurs within first 2 days of menses, with partial response to analgesics (headaches recur); since menses predictable, short-term prevention can be started 2 days before menses and taken daily; triptans can be taken several days before anticipated headache for 5 to 6 days; short-term daily use—1.0-mg bid dose of naratriptan more effective than 2.5 mg bid; more menstrual periods without menstrual migraine seen with naratriptan and frovatriptan; occurrence and frequency of menstrual migraines can be reduced with daily triptan use; since breakthrough headaches may occur, consider using additional dose or adding different class of agent (eg, analgesic, NSAID); monitor on individual basis

Hormonal treatment: case presentation—woman 46 yr of age with history of episodic migraine (2 attacks/mo; no menstrual association); at age 46 yr, menses became irregular, so woman placed on combination hormonal OC (21 active pills and 7 days of placebo pills); migraines increased, particularly during menses when inactive pills taken; treatment—switch to 28-day combination hormonal OC; longer menstrual cycles with fewer drops in estrogen may be helpful

Migraines During Puberty and Pregnancy
Merle L. Diamond, MD, Associate Director, Diamond Headache Clinic, Chicago, IL

Puberty: during puberty, hormonal changes cause more headaches in girls than in boys; significant sleep disorders, dysautonomia, and motion sickness may develop; luteinizing hormone-releasing factor becomes more active in girls; neuroendocrine changes modulate trigeminal nucleus caudalis; estrogen receptors play significant role in emergence of migraine; other chronic somatic disorders increase in frequency; incidence of back pain and temporomandibular joint (TMJ) discomfort increases; odds ratio for pain disorders higher in girls than in boys

Considerations for management of children with migraine: most therapy off-label; substance (eg, alternative drugs, energy drinks) use; eating disorders; erratic and difficult schedules; sexual activity

Migraine in pregnancy: medications often required during pregnancy; help patients make safe decisions; migraine improves in many patients during pregnancy; 25% to 36% of patients treated for migraine of child-bearing age; small percentage of women worsen during pregnancy; 10% of female migraine sufferers have first migraine attack during pregnancy; >50% of pregnancies unplanned; incidence of migraine in pregnancy unknown; study found patients with episodic migraine improved during pregnancy (with spikes later in pregnancy and after delivery), but patients with chronic daily headache did not improve; no increased risk for fetal abnormalities, preeclampsia, or other significant issues; ≈50% of patients improve during first trimester (higher as pregnancy progresses); most migraine problems occur during first trimester; patients can improve after week 14 and continue to improve during remainder of pregnancy; patients with migraine without aura, menstrual-related migraine, and migraine that began with menarche most likely to improve during pregnancy

Drugs and pregnancy: advise patients about safety of medications; ≈10% of congenital abnormalities thought due to environmental exposures; retrospective health maintenance organization (HMO) studies show many medications prescribed to pregnant women (use of over-the-counter drugs may be higher); consider risk for abnormal events; safety of most drugs assessed retrospectively; use resources (eg, Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk and www.reprotox.org); work with gynecologist, obstetrician, patient, and patient’s significant other to build migraine plan; consider consulting genetic pharmacologist; World Health Organization states drugs may be considered safe in pregnancy if not proven dangerous; treatment of migraine avoids dehydration, depression, and anxiety

Nonpharmacologic management: help patients plan and prepare for pregnancy; discuss preventive measures; taper caffeine; encourage exercise and good sleep habits; consider biofeedback; provide prenatal vitamins

Preventive treatment: β-blockers (eg, metoprolol, propranolol) commonly used; SSRIs; antiepileptic drugs (eg, topiramate, gabapentin; category C); speaker generally avoids use of neuronal stabilizers during pregnancy

Acute treatment: acetaminophen safe (consider adding codeine or hydrocodone [category B or C; most retrospective data “somewhat reassuring”]); opioid for episodic treatment reasonable; use butorphanol cautiously (category B; highly addictive and difficult to use; potent); NSAIDs—category B or C (depends on trimester); not used before implantation and during third trimester due to, eg, risk for bleeding

Other therapies: pain management for acute distress; category B drugs include intravenous (IV) metoclopramide (eg, Reglan) and IV diphenhydramine (eg, Benadryl); IV opioids; no clinical data about use of magnesium for episodic migraine in pregnancy, but can be effective and safe; consider occipital nerve blocks and trigger point injections; contraindicated prophylaxis—ergotamine products, including dihydroergotamine (DHE); phenytoin; valproate; lithium; caffeine—effective when used episodically to augment other therapies; avoid excessive use

Pregnancy registries: established for newer recently approved drugs (eg, lamotrigine, bupropion); demonstrate safety in pregnancy; some groups collect prospective data to predict drug safety; sumatriptan registry available in United States since 1992 (nearly 500 infants exposed to sumatriptan during first trimester; no alarming data); registries for naratriptan and combination of sumatriptan and naproxen available

Acute nonsystemic therapies: trigger point injections; occipital nerve blocks; physical therapy; intranasal lidocaine; developmental issues associated with prophylactic use of neuronal stabilizers (eg, topiramate)

Breast-feeding: triptans—classified as category C in breast-feeding; sumatriptan labeled against use during breast-feeding; concentration of sumatriptan and zolmitriptan in breast milk low, but concerned mothers may want to “pump and dump” (ie, pump and discard breast milk while feeding infant baby formula or previously pumped breast milk; half-life of triptans short)