Migraine and Women Dr Manuela Fontebasso General Practitioner

Migraine and Women Dr Manuela Fontebasso General Practitioner, York and GPw. SI in Headache, Headache Clinic, York Hospital

Are hormones important in migraine ? • Prevalence equal in boys and girls before puberty • In adults migraine is 3 times more common in women than men • Studies have shown that the natural fall in oestrogen is a trigger for migraine • Prostaglandin levels rise during menstrual migraine and have been shown to trigger migraine like headache Bille B Migraine in school children Acta Paediatr Scand 1962; 51 suppl 136: 1 - 151 Somerville BW, Neurology 1972; 22: 355 - 365 and 1972; 22: 824 - 828 Fettes I. Post. Grad Med 1997; 101: 67 - 77

Pure Menstrual Migraine without Aura • Defined as • Attacks that occur Day 1 +/- 2 days of each cycle • And at no other time • Most commonly migraine without aura • Affects 10% of all women • Diagnosis is made with diary cards • monitor for 3 cycles • Review and evaluate attack pattern Headache classification Subcommittee of the International Headache Society The International Classification of Headache Disorders 2 nd edition Cephalalgia 2004 24 Suppl 1 1 - 60

Menstrually Related Migraine without Aura • Defined as • Attacks that occur Day 1 +/- 2 days of each cycle • And at other times in the cycle • Diagnosis is made with diary cards • monitor for 3 cycles • Review and evaluate attack pattern Headache classification Subcommittee of the International Headache Society The International Classification of Headache Disorders 2 nd edition Cephalalgia 2004 24 Suppl 1 1 - 60

Migraine and Premenstrual Syndrome • Defined as • attacks that occur in the luteal phase following ovulation • associated with other PMS symptoms • Diagnosis is made with diary cards • monitor for 3 months • PMS symptoms must clear as menstruation starts • Women with PMS may have severe headache not fulfilling IHS criteria for migraine

Pregnancy - 1 • Migraine may occur for the first time in pregnancy • especially migraine with aura • 60 - 70% may experience a reduction in frequency • especially migraine without aura • more likely in women with menstrual migraine • during the second and third trimester Marie- Germaine Bousser & Helene Massiou : Migraine in the reproductive cycle. Chapter 58. The Headaches. Silberstein SD. Migraine in Women. Post Grad Medicine; 97 (4) 147 - 153. Michel Aube. Migraine in Pregnancy. Neurology 1999; 53 (suppl 1): S 26 - S 28 PJ Goadsby J Goldberg SD Silberstein BMJ 2008; 336: 1502 – 1504 Mac. Gregor EA, Migraine in pregnancy and lactation: a clinical review. J Fam Plann Reprod Health Care 2007: 33 (2) 83 to 93

Pregnancy - 2 • 4 - 8% experience a worsening of symptoms • especially those with migraine with aura • Up to 25% may remain the same • May experience rebound effect after delivery • 40% resumed usual pregnancy rate in first post partum week • breast feeding is associated with less migraine Marie- Germaine Bousser & Helene Massiou : Migraine in the reproductive cycle. Chapter 58. The Headaches. Silberstein SD. Migraine in Women. Post Grad Medicine; 97 (4) 147 - 153. Michel Aube. Migraine in Pregnancy. Neurology 1999; 53 (suppl 1): S 26 - S 28 PJ Goadsby J Goldberg SD Silberstein BMJ 2008; 336: 1502 - 1504 Mac. Gregor EA, Migraine in pregnancy and lactation: a clinical review. J Fam Plann Reprod Health Care 2007: 33 (2) 83 to 93

Migraine and the risk of stroke • Migraine with aura increases the risk of ischaemic stroke two fold(1) • Migraine without aura is not associated with an increase ischaemic stroke risk • There are no studies to show that there is an increased risk of stroke in migraine sufferers over the age of 45 years (2) • Annual incidence of stroke in Europe is • 1 to 3 per 100, 000 women under 35 years • 10 per 100, 000 women over 35 years (3) 1. Gudmundsson LA, Scher AI, Aspelund T et al Migraine with aura and risk of cardiovsacular and all cause mortality in men and women/BMJ 2010 341 c 3966 2. The IHS Task Force. Cephalalgia, 2000; 20: 155 – 6 3. Mac. Gregor EA. Hormonal Contraception and migraine. Faculty of Family Planning Fact Sheet. Review no. 2001/01

The combined hormonal contraceptives (CHC), migraine and the risk of stroke • CHC’s are an established risk factor for ischaemic stroke • RR is 16 if you have migraine • Smoking increases the risk of stroke • RR is 10 if you have migraine • Risk is additive • RR is 34. 4 is you take CHC’s and smoke (Tzourio et al BMJ 310: 830 - 833 and Chang et al BMJ 318: 13 - 18)

In the UK: Migraine and Combined Hormonal Contraceptives (CHC) • You can use CHC’s if • There is no aura and no additional risk factors • You can use CHC’s with caution if • There is no aura and one additional risk factor • CHC’s are contraindicated if • • There is aura There is no aura BUT more than one risk factor There are severe and prolonged attacks There is concurrent use of ergot (WHO Improving Access to Quality Care in Family Planning. Medical Eligibility Criteria for Use. Second edition. WHO/RHR/00. 02. ) (Mac. Gregor EA, Guillebaud J. Recommendations for clinical practice. Br J Fam Planning 1998; 24: 53 - 60) (Bousser M-G, Kittner SJ. Oral contraceptives and stroke. Cephalalgia 2000; 20: 183 - 189) (EA Mac. Gregor Migraine and use of combined hormonal contraceptives: a clinical review J Fam Plann Reprod Health Care 2007; 33 (3): 159 – 169 )

Migraine in the Peri and Post Menopause • Migraine prevalence • increases in the peri menopause • decreases in the post menopause • Women who had a spontaneous menopause • Had a migraine prevalence of 7% • Women who had a surgical menopause • Had a migraine prevalence of 27% • + PMS had a migraine prevalence of 44% (Wang SJ, Headache 2003; 43: 470 - 478)

Migraine in the Peri and Post Menopause • In any individual it • May get better • May get worse • May stay the same • Pattern of symptoms may change • Aura without headache

Assessment and Investigations • Careful history to exclude red flag symptoms • Careful examination of patient to exclude focal neurological signs • Is it aura or TIA? • New onset symptoms or change in symptom profile • Diagnostic tests only needed if a secondary headache is suspected • MRI or MRA scan

The acute treatment of the menstrual migraine attack • Menstrual migraine often harder to treat than attacks that occur at other times of the cycle • Menstrual migraine associated with greater degree of disability • Have to find the most effective combination for the individual • may mean using a NSAID and an anti emetic and a triptan • may need to use maximal dose of triptan EA Mac. Gregor Managing Menstrual migraine: A clinical review J Fam Plann Reprod Health Care 2007; 33 (1): 36 - 47

Acute migraine treatment in pregnancy: 1 • Paracetamol, • drug of choice for mild to moderate pain • Aspirin, • safe in first and second trimester, caution at term • NSAID, ibuprofen, not exceeding 600 mg daily • no evidence to show increased risk of malformation or spontaneous miscarriage • caution or avoid after 30 weeks, risk of premature closure of ductus arteriosus and oligohydramnios • Anti-emetics • Buclizine, chlorpromazine, cyclizine, domperidone, metoclopramide and prochlorperazine, no reported adverse effects Mac. Gregor EA, Migraine in pregnancy and lactation: a clinical review. J Fam Plann Reprod Health Care 2007: 33 (2) 83 to 93

Acute migraine treatment in pregnancy: 2 • Ergots, • Contraindicated as cause uterine hypertonicity and vascular disruption increase risk of miscarriage • Triptans, • Safety in pregnancy yet to be confirmed • Women who have used triptans in early pregnancy can be reassured, exposure has not been associated with adverse outcomes • Triptan use during pregnancy is only recommended if no other treatment is effective • Sumatriptan safety data base: 4. 3% risk first trimester birth defects • 3 to 5% risk in general population • Rizatriptan safety data base: similar results but small numbers Mac. Gregor EA, Migraine in pregnancy and lactation: a clinical review. J Fam Plann Reprod Health Care 2007: 33 (2) 83 to 93

Acute migraine treatment while breastfeeding • Paracetamol, • drug of choice • Aspirin, • Avoid, risk of Reyes syndrome • NSAID, • Concentration in breast milk very low • Anti-emetics • Domperidone, pro-kinetic, stimulates prolactin, does not cross blood brain barrier, concentration in breast milk are low • Ergots • avoid, may inhibit lactation Preferred to metoclopramide Mac. Gregor EA, Migraine in pregnancy and lactation: a clinical review. J Fam Plann Reprod Health Care 2007: 33 (2) 83 to 93

Triptan use while breastfeeding • Consider • • bioavailability amount of medication in breast milk limited data available Summary of product characteristics usually suggest • caution • avoid breast feeding for 12 to 24 hours after treatment • Sumatriptan • Most extensive data base • Low level of excretion in breast milk (0. 5% of oral dose) • Eletriptan • One study, 80 mg dose, 0. 02% of dose in breast milk Mac. Gregor EA, Migraine in pregnancy and lactation: a clinical review. J Fam Plann Reprod Health Care 2007: 33 (2) 83 to 93

Pure Menstrual Migraine without Aura – Use of NSAID or Percutaneous/Transdermal oestrogen Need to have regular periods • Use any NSAID • Naproxen 500 mg up to bd or mefenamic acid 500 mg up to qds • Use any oestrogen patch or gel • transdermal oestrogen 100 mcg or oestradiol gel 1. 5 mg • Start 2 - 3 days before expected onset of attack and use for 7 days • Can extend NSAID into period if the patient has dysmenorrheoa EA Mac. Gregor Managing Menstrual migraine: A clinical review

Pure Menstrual Migraine without Aura Migraine in pill free week • Use oestrogen dominant pill • Marvelon or Dianette • Tricycle the COCP • Take three packs consecutively • Use NSAID daily in pill free week • Use top up oestrogen in pill free week EA Mac. Gregor Managing Menstrual migraine: A clinical review J Fam Plann Reprod Health Care 2007; 33 (1): 36 - 47

Migraine, HRT and the peri-menopausal women • Ideally use patch or gel • If she has NOT had a hysterectomy • Cyclical HRT • Oestrogen and progestogen preparation, with progestogen for 14 days in each cycle • If she HAS had a hysterectomy • Can use oestrogen alone

Migraine and HRT and the post-menopausal women • Ideally use patch or gel • If she has NOT had a hysterectomy and it is more than 12 months since her last period • Continuous combined HRT • Combined oestrogen and progestogen • If she HAS had a hysterectomy • Can use oestrogen alone

Migraine and HRT - 1 When using patch or gel Oestrogen patch 25 mcg • Start at lowest possible dose • Matrix patch offers most dose flexibility • because you can cut it up • Titrate the dose up slowly Could start with a quarter patch By a quarter patch weekly or monthly

Migraine and HRT - 2 • If unable to tolerate standard preparation • could use oestrogen patch and dydrogesterone or medroxyprogesterone for 14 days in each cycle • Could use Levonorgestrel releasing IUS as progestogen source to give period free HRT in the peri or post menopausal woman BUT what about the risks?

Migraine, HRT and breast cancer risk • Background incidence per 1000 women not using HRT • 50 to 59 yrs • 60 to 69 yrs 10 over 5 yrs 20 over 10 yrs 15 over 5 yrs 30 over 10 yrs • Additional cases per 1000 women using oestrogen only Additional cases HRT • 50 to 59 yrs • 60 to 69 yrs 2 for 5 yrs use 6 for 10 yrs use 3 for 5 yrs use 9 for 10 yrs use • Additional cases per 1000 women using combined HRT Additional cases • 50 to 59 yrs • 60 to 69 yrs 6 for 5 yrs use 24 for 10 yrs use 9 for 5 yrs use 36 for 10 yrs use Adapted from BNF 58 September 2009

Migraine, HRT and endometrial cancer risk • Background incidence per 1000 women not using HRT • 50 to 59 yrs • 60 to 69 yrs 2 over 5 yrs 4 over 10 yrs 3 over 5 yrs 6 over 10 yrs • Additional cases per 1000 women using oestrogen only Additional cases HRT • 50 to 59 yrs • 60 to 69 yrs 4 for 5 yrs use 32 for 10 yrs use 6 for 5 yrs use 48 for 10 yrs use • Additional cases per 1000 women using combined HRT Additional cases • 50 to 59 yrs • 60 to 69 yrs 0 for 5 yrs use 0 for 10 yrs use Adapted from BNF 58 September 2009

Migraine, HRT and ovarian cancer risk • Background incidence per 1000 women not using HRT • 50 to 59 yrs • 60 to 69 yrs 2 over 5 yrs 4 over 10 yrs 3 over 5 yrs 6 over 10 yrs • Additional cases per 1000 women using oestrogen only Additional cases HRT • 50 to 59 yrs • 60 to 69 yrs <1 for 5 yrs use 1 for 10 yrs use <1 for 5 yrs use 2 for 10 yrs use • Additional cases per 1000 women using combined HRT Additional cases • 50 to 59 yrs • 60 to 69 yrs <1 for 5 yrs use 1 for 10 yrs use <1 for 5 yrs use 2 for 10 yrs use Adapted from BNF 58 September 2009

Migraine, HRT and VTE risk • Background incidence per 1000 women not using HRT • 50 to 59 yrs • 60 to 69 yrs 4 over 5 yrs 5 over 5 yrs • Additional cases per 1000 women using oestrogen only Additional cases HRT • 50 to 59 yrs • 60 to 69 yrs 2 for 5 yrs use Especially in first year of use 2 for 5 yrs use • Additional cases per 1000 women using combined HRT Additional cases • 50 to 59 yrs • 60 to 69 yrs 7 for 5 yrs use 10 for 5 yrs use Adapted from BNF 58 September 2009

Migraine, HRT and stroke risk • Background incidence per 1000 women not using HRT • 50 to 59 yrs • 60 to 69 yrs 4 over 5 yrs 9 over 5 yrs • Additional cases per 1000 women using oestrogen only HRT initiated in the Additional cases HRT • 50 to 59 yrs • 60 to 69 yrs 1 for 5 yrs use 3 for 5 yrs use perimenopause is not associated with an increased stroke risk 1 • Additional cases per 1000 women using combined HRT Additional cases • 50 to 59 yrs • 60 to 69 yrs 1 for 5 yrs use 3 for 5 yrs use Adapted from BNF 58 September 2009 1 EA Mac. Gregor Migraine, the menopause and hormone replacement therapy: a clinical review J Fam Plann Reprod Health Care 2007; 33 (4): 245 - 249

Migraine, HRT and coronary heart disease • Background incidence per 1000 women not using HRT • 70 - 79 yrs 29 - 44 over 5 yrs • Additional cases per 1000 women using combined HRT Additional cases in women who start HRT more than 10 yrs after the • 70 – menopause 79 yrs 15 for 5 yrs use HRT initiated in the perimenopause is not associated with an increased cardiovascular risk 1 Adapted from BNF 58 September 2009 1 EA Mac. Gregor Migraine, the menopause and hormone replacement therapy: a clinical review J Fam Plann Reprod Health Care 2007; 33 (4): 245 - 249

Conclusion In any patient with migraine the principles of management should be to • • • adopt a holistic approach to care involve the patient in the decision making process find the most effective acute treatment option consider standard prophylaxis options remember that hormonal or similar targeted options • do not suit everybody • may not be a first line choice