Hormones and Migraine

Educational Objectives

The goal of this program is to improve diagnosis and treatment of headache. After hearing and assimilating this program, the clinician will be better able to:

1. Choose adequate therapies for migraine prophylaxis for patients in the perimenstrual period.
2. Advise patients about the benefits and risks associated with the use of oral contraceptives for the treatment of migraine.

Summary

Epidemiology: migraine affects 25% of women of reproductive age; female sex hormones play role in pathogenesis of migraine; prevalence higher during reproductive years (menstruation, postpartum period, and perimenopause) and lower in second and third trimesters of pregnancy and in postmenopausal years

Risk factors: retrospective study of 1200 patients showed that hormones second most common trigger of migraine attacks (after stress); incidence of migraine higher in women than in men over lifespan

Onset: onset of migraine with aura starts later in girls (12-13 yr) than in boys (<5 yr); migraine without aura starts at older age in both sexes (14-17 yr in girls and 10-11 yr in boys); ≈53% of girls experience worsening of migraine at age of menarche; data of 6000 adolescent girls enrolled in Growing Up Today Study showed that early menarche increases risk for developing migraine

Pathophysiologic mechanisms: decrease in estrogen levels in late luteal phase of menstrual cycle triggers migraine; relative risk for migraine during menstrual cycle highest during period 6 days before start of cycle to 2 days afterward; peak of migraine coincides with drop in estrogen levels

Menstrual migraine: refers to attacks that occur in at least 2 of 3 consecutive menstrual cycles and exclusively from 3 days before to 3 days after beginning of menstrual cycle; accounts for 7% to 14% of migraine cases in women

Menstrually related migraine: typically occurs from 3 days before to 3 days after onset of menses; unlike menstrual migraine, can occur at other times during cycle as well; accounts for 60% to 70% of migraine cases in women

Treatment of menstrually related migraine: typically resistant to abortive treatment; prophylactic therapies — include antihypertensive, anticonvulsant, and antidepressant medications; hormonal prophylaxis helpful as well

Perimenstrual prophylaxis: frovatriptan has longest half-life (25 hr), but naratriptan, sumatriptan, and zolmitriptan also efficacious; initiate therapy 2 days before menstruation and continue 5 to 7 days; naproxen (550 mg twice daily) used for 7 to 14 days; high-dose naproxen associated with risk for gastrointestinal bleeding

Hormonal therapies: transdermal gels — used for 7 days (beginning 10 days before ovulation); oral contraceptives (OCs) — extended cycle (without placebo week) used for 3 mo; adding transdermal gel during placebo week after extended cycle can attenuate decrease in estrogen; progestin-only pills and intrauterine devices (IUDs) and standard-cycle OCs ineffective; low-dose (10 μg estrogen) continuous hormone contraception key to preventing migraines; agents with 10 μg of estrogen — ethinyl estradiol and levonorgestrel (eg, Amethyst, Lybrel, Portia), levonorgestrel-ethinyl estradiol and ethinyl estradiol (eg, Amethia, LoSeasonique, Quasense), estradiol valerate and estradiol valerate-dienogest (Natazia), and norethindrone acetate and ethinyl estradiol (Lo Loestrin); research shows hormonal prophylaxis effective in reducing menstrually related migraine and overall burden of headache

Risk for stroke: migraine is independent risk factor for stroke; use of OCs further increases risk; however, absolute risk for ischemic stroke low in women of reproductive age; American College of Obstetricians and Gynecologists and World Health Organization advise against use of OCs in patients with migraine with aura; International Headache Society state clinicians must decide if triptans appropriate option; data showing increased risk for stroke in women with migraine who use OCs generated by outdated studies with high-dose estrogen formulations; overall, studies of relationship between OCs and risk for stroke have shown that high estrogen content (>50 µg) increases risk for stroke, whereas low estrogen content (<50 µg) carries low or no risk for stroke; recent study showed that joint effect of hormonal contraceptives and migraine with aura associated with 6-fold increased risk for ischemic stroke compared with neither risk factor; use of OCs did not substantially increase risk for stroke in women with migraine without aura

Pregnancy: acetaminophen (eg, Anacin-3, Tactinal, Tylenol), memantine, metoclopramide, diphenhydramine (eg, Benadryl, Diphedryl, Sominex), ondansetron (Zofran, Zuplenz), and subcutaneous lidocaine considered safe treatment options; several antihypertensive agents, tricyclic antidepressants, and antiepileptic medications have shown possible risks in animal trials; lisinopril and topiramate carry risk; risks associated with valproic acid and ergots outweigh benefits; nonsteroidal anti-inflammatory drugs (NSAIDs) safe in second trimester but contraindicated in third trimester because of potential fetal complications; use of NSAIDs close to becoming pregnant can cause spontaneous abortion; discontinue triptans once pregnancy confirmed

Postpartum period: rapid decline in estrogen levels triggers migraine; preventive therapies safe for lactating women include verapamil, propranolol, magnesium, and vitamin B2; safe rescue medications include sumatriptan and eletriptan; avoid long-acting triptans (eg, frovatriptan); prednisone and subcutaneous lidocaine safe as rescue therapies

Perimenopausal period: standard migraine prophylaxis used; evidence supporting use of hormonal therapies and chemical menopause insufficient; OCs that contain estrogen increase risk for breast cancer; hormone replacement therapy can trigger new-onset migraine; oral estrogen replacement treatments can exacerbate migraine; continuous progestin therapy better tolerated than cyclic regimens; levonorgestrel-releasing IUDs (eg, Kyleena, Mirena, Skyla) effective; nonhormonal therapies — paroxetine 7.5 mg and gabapentin effective in some studies

Readings

Bousser MG, Kittner SJ: Oral contraceptives and stroke. Cephalalgia 2000;20(3):183–89; Champaloux SW et al: Use of combined hormonal contraceptives among women with migraines and risk of ischemic stroke. Am J Obstet Gynecol 2017;216(5):489.e1–e7; Kelman L: The triggers or precipitants of the acute migraine attack. Cephalalgia 2007;27(5):394–402; Maleki N et al: Age at menarche and risk of developing migraine or non-migraine headaches by young adulthood: a prospective cohort study. Cephalalgia 2017;37(13):1257–63.

Disclosures

For this program, the following has been disclosed: Dr. Bucklan is a consultant for Allergan and Bausch & Lomb and has received grant and research support from Genentech (a member of the Roche Group). The members of the planning committee reported nothing to disclose. Dr Bucklan presents information in her lecture related to off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Bucklan spoke at 2019: Restoring Neurological Function, presented by the Cleveland Clinic Foundation Center for Continuing Education and held September 20, 2019, in Warrensville Heights, OH. For information about upcoming CME conferences presented by the Cleveland Clinic Foundation Center for Continuing Education, please visit clevelandclinicmeded.com. The Audio Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

OB671402

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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