Jessica Ailani MD FAHS Director, Georgetown Headache Center Associate Professor Neurology Medstar Georgetown University Hospital
Honorarium from Current Pain and Headache Reports; Section Editor Unusual Headache Syndromes Honorarium for Speaking from Allergan and Avanir
Relate how hormones can play a role in migraine Evaluate patients with migraine related to hormones and diagnose menstrual migraine vs. menstrual related migraine Apply evidence when choosing treatment options for menstrual migraine Evaluate the use of oral contraceptives in patients with migraine
Women s health concern 3 month prevalence 19.1% 1 28 million women in the US have migraine 2 1 in 4 will experience a migraine in their lifetime 2 Triggered by Hormones 60% of woman with migraine report association with menses [range between 3-76%] 3,4 Migraine risk is greatest between day -2 to day +3 4 Twofold increase risk of migraine on 1 st 3 days of bleeding compared to rest of cycle 4 1. Burch R, et al. The prevalence and burden of migraine and severe headache in the United States: updated statistics from government health surveillance studies. Headache 2015;55:21-34 2. https://migraineresearchfoundation.org/about-migraine/migraine-facts/ 3. Pavlock JM, et al. Burden of migraine related to menses: results from the AMPP study. Journal of Headache and Pain 2015;16:24 4.MacGreggor A. Migraine management during menstruation and menopause. Continuum lifelong learning in Neurology 2015;21:990-1003
Menstrual migraine can be more severe and difficult to treat 1 Higher burden and impact on functioning compared to non-menstrual migraine 1 Longer duration migraine 2 More frequently with severe nausea 2 Menses can be a trigger for migraine without aura, but not usually migraine with aura 3 1.Pavlock JM, et al. Burden of migraine related to menses: results from the AMPP study. Journal of Headache and Pain 2015;16:24 2.Vetvik KG et al. Are menstrual and non menstrual migraines attacks different? Curr Pain Headache Rep 12:462-467 3.MacGreggor A. Migraine management during menstruation and menopause. Continuum lifelong learning in Neurology 2015;21:990-1003
Puberty: Average age 10-11 in girls, lasting up to 4 years Increase in sex steroids Menarche: Average age 12-15 Menopause: Average age 51 Hormones can fluctuate for 4-5 more years Can be precipitated by several years of hormonal fluctuation (Peri menopause) MacGreggor A. Migraine management during menstruation and menopause. Continuum lifelong learning in Neurology 2015;21:990-1003. https://en.wikepedia.org/wiki/menstrual_cycle
Three phases in 2 cycles Ovarian cycle Follicular phase- gradual rise in estrogen Ovulation- peak in estrogen prior Luteal phase- fall in estrogen Fall in estrogen in late luteal phase may trigger migraine Prostaglandins may play a role in menstrual migraine- increase threefold in luteal phase Uterine cycle Menses- sudden drop in estrogen prior Prostaglandins increase in the first 48 hours of menses Proliferative phase Secretory phase MacGreggor A. Migraine management during menstruation and menopause. Continuum lifelong learning in Neurology 2015;21:990-1003. https://en.wikepedia.org/wiki/menstrual_cycle
http://www.bbc.co.uk/schools/gcsebitesize/science/aqa_pre_2011/human/hormonesrev3.shtml
24 yo woman presents with headaches related to menses. She notes every month she gets a headache the day prior to her period. The headache is throbbing over her left temple and into her eye. Pain is severe with nausea, light sensitivity and trouble concentrating. She will occasionally vomit. She is usually bedridden the first day. Headache dulls with ibuprofen, but does not resolve, and can last for 3 days. She misses 1 day of work per month due to headache.
What is the diagnosis? What should we ask her to do to confirm the diagnosis? What should we advise her?
Headache only with menses Are menses predictable? Is headache onset predictable? Keep a calendar for 3 months to confirm headache with every menses People can under or overemphasis link to menses Want to document start of migraine is consistent with each or most cycles Important to ask about current and prior OCP use Important to ask about other medical conditions to help guide your treatment plan GI/CV/Renal disease Confirm aura or no aura
Attacks in a menstruating woman fulfilling criteria for migraine without aura Documented and prospectively recorded evidence over at least 3 consecutive cycles has confirmed that attacks occur exclusively on days -2 to +3 of menstruation in at least 2 of the 3 menstrual cycles and at no other times of the cycle Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders 3 rd edition (Beta). www.ichd-3.org
At least five attacks fulfilling criteria B-D Headache attacks lasting 4-72 hr (untreated or unsuccessfully treated) Headache has at least two of the following four characteristics: 1. unilateral location 2. pulsating quality 3. moderate or severe pain intensity 4. aggravation by or causing avoidance of routine physical activity (eg, walking or climbing stairs) During headache at least one of the following: 1. nausea and/or vomiting 2. photophobia and phonophobia Not better accounted for by another ICHD-3 diagnosis. Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders 3 rd edition (Beta). www.ichd-3.org
Mini prevention Treating daily prior to start of symptoms and for some time after migraine resolves [Not for entire month] Can be done with NSAIDS or Triptans or Hormones Keeping calendar, regular and predictable menses, good response to the medication that will be used as preventive
Naproxen 550mg BID starting 7 days prior to menses to day 6 of menses 1 Only NSAID with strong evidence 2 Small study with nimesulide 100mg TID for 10 days during menses 3 Other NSAIDS can be tried Avoid with GI/Renal/CV disease Monitor for possible development of medication overuse Less likely with NSAIDS 4 1.Sances et al. Naproxen Sodium in Menstrual Migraine Prophylaxis: A Double-Blind Placebo Controlled Study. Headache 1990;30:705-709 2. Nierenburg HC et al. Systematic Review of Preventive and Acute Treatment of Menstrual Migraine. Headache 2015;55:1052-1071. 3.Giacovazzo M, et al. Nimesulide in the treatment of menstrual migraine. Drugs 1993;46:140-141. 4.Bigal ME, et al. Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population based study.
Level A Frovatriptan 5mg BID day 1, then 2.5mg BID day 2-6, starting 2 days prior to start of migraine No increased risk of post treatment migraine Level B Naritriptan 1mg BID for 6 days, starting 3 days prior to menstrual migraine Can increase risk of migraine immediately following treatment Zolmitriptan 2.5mg BID/TID for 7 days, starting 2 days prior to menses Not assessed for post treatment migraine Poor evidence Open label studies using sumatriptan Results positive Nierenburg HC et al. Systematic Review of Preventive and Acute Treatment of Menstrual Migraine. Headache 2015;55:1052-1071. MacGreggor A. Migraine management during menstruation and menopause. Continuum lifelong learning in Neurology 2015;21:990-1003
Estradiol gel 1.5mg daily for 7 days, starting between 2-5 days prior to menses Goal to maintain luteal phase estrogen level Increased risk of post treatment migraine Level C Nierenburg HC et al. Systematic Review of Preventive and Acute Treatment of Menstrual Migraine. Headache 2015;55:1052-1071. MacGreggor A. Migraine management during menstruation and menopause. Continuum lifelong learning in Neurology 2015;21:990-1003
Extended cycle birth control Use of combined oral contraceptives Skip placebo Stop OCP for 3 days then restart if breakthrough bleeding occurs Use estrogen supplementation during placebo (10mcg oral ethinyl estradiol, 0.9mg oral conjugated equine estrogens, 100mcg estradiol patches, 2g estradiol gel) Levonorgestrel-releasing intrauterine system (IUD) Limited to no menses Nierenburg HC et al. Systematic Review of Preventive and Acute Treatment of Menstrual Migraine. Headache 2015;55:1052-1071. MacGreggor A. Migraine management during menstruation and menopause. Continuum lifelong learning in Neurology 2015;21:990-1003
Calendar for 3 months, menstrual correlation should be there for 2 out of 3 months Migraines and menses should be predictable Instead of daily preventive, consider mini prevention around menses Consider patients wishes and co-morbidities when it comes to nsaids vs. triptans vs. hormones Watch for medication overuse headaches (esp. triptans)
28 yo woman with a history of pure menstrual migraine. Now she notes that along with migraine with menses for 3 days, she is getting migraines up to 5 other days a month. These are not as severe as menstrual related migraine, but still left sided with nausea and light sensitivity. She notes triggers of sleep deprivation, stress, skipped meals, and weather changes.
What is her diagnosis now? What makes this case more challenging? What are some concerns we should have about her use of abortive medications? Can an oral contraceptive improve her migraines?
Menstrual migraines Migraines at other times of the month Frequency of migraines places her at risk for medication overuse headaches and chronic migraine She should calendar ALL headaches with treatment Is she using OTC meds for regular headaches How many days do you NOT have a headache in the month
Attacks, in a menstruating woman, fulfilling criteria for Migraine without aura Documented and prospectively-recorded evidence over at least three consecutive cycles has confirmed that attacks occur on days 2 to +3 of menstruation in at least two out of three menstrual cycles, and additionally at other times of the cycle. Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders 3 rd edition (Beta). www.ichd-3.org
Lifestyle changes Regular sleep (sleep and wake times), eating regularly (3-5 meals per day), stress management (Mindfulness based stress reduction/regular exercise) Consider daily prophylactic When headaches are 4 or more days a month, with some disability 1 Guidelines for migraine prevention 2 Divalproex/sodium valproate, Metoprolol, Propranolol, Timolol, Topirmate, Petasites Mini prevention may still be an option with menses Keep good calendar documenting treatment Limit triptan use to less than 10 days a month Limit other OTC use, especially combined analgesics OCP less likely to help as will not impact non menstrual migraines 1. Estemalik E, et al. Preventive treatment in migraine and the new US guidelines. Neuropsychiatr Dis Treat 2013;9:709-720 2. Silberstein SD, et al. Evidence-based guideline update: Pharmacologic treatment for episodic migraine prevention in adults. Neurology 2012;78:1337-1345.
Encourage patients to keep headache calendar Document ALL headaches Document ALL meds used (OTC included) Prevent migraines Lifestyle changes Prophylaxis Limit overuse of abortive medications OCP unlikely to help
32 yo woman with history of menstrualy related migraine has noticed since after the birth of her second child, she is having migraines now occurring monthly. With her headache calendar, she is able to recognize they are occurring during the time she takes the birth control pills that are a different color from the rest of the pack. She has been doing well with migraines the rest of the month. The migraine that occurs monthly is severe and lasts for 3 days. She is bedbound and does not find her mini prevention with naproxen to be helpful.
What is her diagnosis? What is the effect of OCP on migraines? What can we advise?
Placebo pill triggering migraine Mini prevention with NSAID no longer effective Occurring every month Has been on this OCP since prior to first pregnancy
Headache or migraine developing within five days after daily consumption of exogenous estrogen for three weeks or longer, which has been interrupted (usually during the pill-free interval of combined oral contraception or following a course of replacement or supplementary estrogen). It resolves spontaneously within three days in the absence of further consumption. Diagnostic criteria: A. Headache or migraine fulfilling criterion C B. Daily use of exogenous estrogen for 3 weeks, which has been interrupted C. Evidence of causation demonstrated by both of the following: 1. headache or migraine has developed within 5 days after the last use of estrogen 2. headache or migraine has resolved within 3 days of its onset D. Not better accounted for by another ICHD-3 diagnosis. Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders 3 rd edition (Beta). www.ichd-3.org
Low dose estrogen or patch during placebo pills Reduce the drop in estrogen, reduce chance of migraine Skip placebo pills, scheduled menses every 3 months NSAIDS or Triptans during placebo pills Change to extended cycle pills vs. Levonorgestrel-releasing intrauterine system Use an OCP with fewer placebo days Consider stopping OCP and see what happens to migraine www.mayoclinic.org/diseases-conditions/chronic-daily-headaches/in-depth/headaches/art-20046729?pg=1
OCP can help pure menstrual migraine, but has the potential to worsen migraines vs. not affect migraines Sometimes trying a different type of OCP can improve migraines Sometimes 3 month break off OCP can help determine if it is triggering more migraines
Combined OCP associated with twofold increased risk of stroke This is in older preparations with higher dose estrogen Unclear risk with current lower estrogen preparation pills Still, screen for CV risk factors in patients you are considering OCP Migraine with aura associated with twofold increased risk of stroke Risk vs. benefit when using OCP in patients with migraine with aura Avoid high dose estrogen Consider progesterone only pill vs. Levonorgestrel-releasing intrauterine system
Decided to change to mini prevention with frovatriptan, worked well with use for 5 days a month, starting day prior to start of placebo pill and stopping on day 2 of new OCP pack She had been off OCP while trying for pregnancy and felt migraines were worse (menstrual migraines were beginning to last for 5-7 days) She had tried extended cycle OCP in the past and noted frequent breakthrough bleeding past the 3 months of initiation Was considering 3 rd pregnancy in 2 years, wanted to avoid IUD
Estrogen withdrawal headache related to abrupt cessation of estrogen that has been continuous for 3+ weeks Consider extended cycle vs. continuous OCP to skip estrogen drop Consider mini-prevention during placebo, especially if patient does not want to change OCP Consider trial off OCP for 3 months to see what occurs with migraine