Disclosures. Learning Objectives. Treatment Of Menstrual Migraine 11/10/2017. Research grants Aralez, Allergan

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1 Treatment Of Menstrual Migraine Christine Lay, MD Director, Centre for Headache Associate Professor University of Toronto Disclosures Research grants Aralez, Allergan Unrestricted educational grants Aralez, Allergan Speakers Bureau/Ad Board Allergan, Novartis Learning Objectives 1. To understand pure menstrual migraine and menstrually related migraine 2. To develop a treatment strategy for acute and mini prophylaxis 3. To appreciate the implications of hormonal therapy in a migraineur 1

2 Hormones & Migraine Migraine: Higher Prevalence in Women Prevalence (%) Females Males hormonal factors, including a sudden decrease in plasma estradiol occurring at menstruation gender difference after menopause suggests that other factors are also involved >80 Age (years) Breslau N, Rasmussen BK. Neurology. 2001;56:S4S12. Chart adapted from Henry P et al. Cephalalgia. 1992;12: Lifelong Hormonal Changes Young girls Menarche Menstrual Migraine Oral Contraceptive Use Pregnancy and Breast Feeding Peri/Menopause Hormone Replacement Therapy 2

3 Young Girls and Menarche Prior to puberty, prevalence is less than in boys As menarche approaches frequency may increase Most common time to experience first migraine May be underrecognized Irregular cycles contribute to more headache Menstrual migraine often starts in teens Ovarian Hormones and Migraine 80% female migraineurs have 1st migraine between 1039 yrs Drop in estrogen before menses triggers migraine (Somerville 1970 s) Estrogen increases serotonin synthesis Estrogen decreases serotonin degradation Estrogen affects PGs, Mg, NO Estrogen and Migraine women have lower pain thresholds as estrogen levels increase, so does pain threshold as estrogen drops, so does pain threshold pain thresholds change at: ovulation, menstruation and pregnancy estrogen may facilitate kindling? facilitates chronification of headache Hellstrom, Lundberg Phys Beh

4 Estrogen and Serotonin estrogen influences serotonin as estrogen rises so does serotonin with menses and postdelivery estrogen & serotonin levels fall may relate to comorbid depression and anxiety both more common in women and in migraineurs both may have monthly cyclical phases both linked to serotonin Marcus, Pain 1995 Brandes, Marcus 2004 ICHD III Beta 4

5 Menstrual Migraine typical HA onset is day 2 to day +3 migraine without aura 6070% of women pure menstrual migraine exclusively with menses menstrually related migraine (MRM) migraine at menses and at other times in month premenstrual syndrome (PMS) headache onset day 7 to day 0 ICHD III Beta Cephalalgia Pattern of Headache At Menses Premenstrual headache (Days 7 to 2) Menstrual migraine (Days 2 to +3) Menstrual migraine peaks near menses Cycle Days Loder EL et al. Migraine in Women. BC Decker Inc; (Day menses begins) Weeks 23 Classification of Migraine at Menses Relationship of Migraine Attacks to the Menstrual Cycle Pure Menstrual Migraine 10% Unrelated to Menses 40% MRM 50% Loder EL et al. Migraine in Women. BC Decker Inc; 2004:

6 Menstrual Migraine Perceived by MDs and pts as: more severe longer duration harder to treat but not confirmed in earlier diary studies Study of MRM and nonmrm in same patients: 2.5 x more likely for migraine in first 3 days of cycle 3x more likely to report it as severe Stewart et al. JAMA MacGregor Neurology 2004 Menstrually Related Migraine 60% of women (pure MM and MRM) occurs on days 2 to +3 produce longer workrelated disability more severe less responsive to acute Rx than nonmm Ineffective Rx leads to increased risk of MOH chronification of HA Allais G, Benedetto C. Neurol Sci. 2004;25 (suppl 3):S229S231 Granella F et al. Cephalalgia. 2004;24: MacGregor EA, Hackshaw A. Neurology. 2004;63: Calhoun, Ford Headache 2008 Preventative Treatment Lifestyle Modification Sleep routine Bed and wakeup time Same routine on weekends No electronics at least 1 hr prior to bed Sleep quality assess for it Hydration and eating routine 1.5 L or >, avoiding/reducing caffeine, colours, sweeteners, flavourings, high fructose drinks/foods One medium coffee popular chain + 9 cans coke caffeine Whole foods, frozen>canned Exercise Reduces migraine burden Improves mood Increases BDNF brainderived neurotrophic factor 6

7 Preventative Treatment Stress Management Mindfulness/CBT/Biofeedback Its different than relaxing and quiet time It is active therapy Reducing stress promotes wellness over sickness Empowers patients Promotes brain cell division which leads to brain repair Free Apps Stop Breathe Think Headspace Smiling Mind Pacifica Mindfulness Device The Muse (choosemuse.com) Case 27 year old woman History of infant colic and motion sickness migraine since age 13 migraine now 4 times /month, one severe attack, without aura, one day before her period Exam normal Questions to ask? Diagnosis? Therapy options? Case Questions PMHx, vascular risk factors, smoking, pregnancy planning, any h/o miscarriage, on OCP? Diagnosis Menstrually Related Migraine Therapy Acute +/ preventative options 7

8 Acute Therapy NSAIDs early/mild migraine or combination Rx mefenamic acid 500mg TID prn naproxen sodium 550mg BID prn diclofenac K+ powdered solution celecoxib 200mg BID prn ASA 3 x 325mg +/ metoclopramide nasal ketorolac J Fam Practice 2014, Neurology 2012 Acute Therapy Triptans injectable sumatriptan* for rapid onset +/ vomiting zolmitriptan or sumatriptan nasal spray* for fast action rizatriptan, almotriptan, eletriptan, zolmitriptan, sumatriptan +/ naproxen naratriptan, frovatriptan potentially recurrence* DHE 4 sprays over 15 minutes Combination therapy is most often required Triptan + NSAID + antiemetic +/ magnesium 300mg CNS Drugs, 2005,Current Pain HA Rep 2010 ShortTerm Prevention: NSAIDs predictability lends itself to shortterm Rx dosing range day 7 to +6 most often range is day 5 to day +5 naproxen sodium mg BID mefenamic acid 500 mg tid nabumetone mg BID Sances G et al. Headache. 1990;30; Mira M et al. Obstet Gynecol. 1986;68: Allais, 2007 AlWaili NS. Eur J Med Res. 2000;5:

9 ShortTerm MM Prevention: Triptans Sumatriptan 25 tid x 5 days open label Naratriptan 1mg bid x 5 days RCT Zolmitriptan 2.5mg bid x 7 days RCT Frovatriptan 2.5mg bid x 6 days RCT Rx begins 2 days before migraine Newman 1998, Tuchman 2008, Newman 2001, Silberstein 2004 Hormonal Prophylaxis since estrogen withdrawal provokes MRM, supplementation should improve migraine migraine may occur 5 d after stopping supplementation Estrogen 48 hours prior to MRM x 7 days lower doses not effective transdermal estradiol 100µg estradiol gel 1.5mg in 2.5g gel OCP oral dosing less effective, but noncycling is option Pfaffenrath 1993, LaGuardia 2005, MacGregor 2006 Magnesium MiniPrevention Begin day 15 of cycle mg daily Less intense pain Fewer number of headache days Facchinetti

10 Contraceptives OCP Low dose>high dose Monophasic>Biphasisc>Triphasic Noncycling consider Seasonale Estrogen patch addon in placebo week Patch Vaginal Ring IUD Barrier Standard Prevention Some patients may need preventative therapy Possible benefit from increasing dose of their migraine preventative med around menses Begin a few days before MRM and continue for 710 days Peri/Menopausal Menstrual Migraine 10

11 Numerous hormonal fluctuations in the transition to menopause FMP Final Menstrual Period Pavlovic et al. Neurology 2016 Jul 5;87(1):4956,.; Jaffe H. NAMS Oct Migraine and Menopausal Transition 8 to 13% develop new onset migraine during MT Prevalence of migraine ranges from 10% to 29% during MT Prevalence the highest in late perimenopausal group (31% vs 16.7 in premenopausal) Over 60% of women in menopause clinics report headache Migraine prevalence can peak in late perimenopause and decline following last period But migraine can often persists after last period Hodson J, Climacteric. 2000;3(2):119124; Granella F,. Headache.1993;33(7):385389; Ripa et al. Int J Womens Health Aug 20;7:77382 Approaching Menopause Migraine prevalence, % Migraine often improves > age 50+ But HA often worsens prior to this Orderly pattern of estrogen and progesterone fluctuation lost Episodic fluctuations in levels Worsening HA may herald perimenopause New onset or return of migraine Adapted with permission from Stewart WF et al. JAMA. 1992;267: Copyright 1992, American Medical Association. All rights reserved. 11

12 Frequent Questions From Patients Will my headaches be better when my period stops? In majority but takes time and must address MOH If I have headaches, can I take the pill or HRT? depends For HRT, what dose and preparation is best? Variable, but lose dose and consistency are best Can I still take triptans after menopause? Most likely Should I have hysterectomy? Migraine and HRT Migraine can worsen or not change depending on Preparation used and route of delivery Dose used Continuous vs. intermittent dosing Concomitant use of progestin Worsening is more likely with tablets than transdermal preparations Worsening of migraine on HRT could be marker HRT not typically Rx for migraine only if so recommend short term use short term use to stabilize levels may help if migraine worsened by HRT reduce dose use noncycling switch from conjugated estrogen to pure estradiol switch from oral to patch therapy switch from synthetic to bioidentical 12

13 Menopausal Migraine: will surgery help? BETTER Spontaneous menopause 67% Surgical menopause 33% WORSE Spontaneous menopause 9% Surgical menopause 67% Menstrual Migraine Can begin in puberty and persist through menopause Document discussion around pregnancy issues Requires more aggressive Rx than nonmrm Be mindful of MOH Add in miniprevention if refractory Consider bump in standard migraine prevention around MRM 13