Why It’s Not About Hormones!

Some Menstrual Migraine Facts

Migraine is the second most common headache condition next to Tension-type Headache.  Up to one fourth of all women have migraine, and of those, 60% experience migraine without aura episodes in at least two thirds of their menstrual cycles.  Menstrual Migraine is in the top five disabling conditions for women and is now classified as either ‘Pure menstrual’ Migraine or ‘Menstrual-related’ Migraine.

Why Hormones are Assumed to be the Problem

There is no doubt that a fall in oestrogen levels triggers headache for some women and for this reason it is assumed that hormones are the problem; those poor hormones… they are blamed for (almost) everything!  Hormones are not the problem.  Yes, you read that correctly, hormones are not the problem.

Clinical Observations

I have always been intrigued by a couple of clinical observations.

1. Why do a significant number of women not only experience headache around Day 1 (fall in/decreased oestrogen) of their cycle but also at mid cycle/ovulation when there is increased estrogen?

and

2. Why is menstrual migraine often just on one side? Surely hormones affect both sides of the head equally – unquestionably then a headache caused by hormones would be bilateral (on both sides of the head simultaneously) or ‘all-over’.

What Research Has Confirmed

Furthermore research has confirmed that the hormonal profiles of women experiencing menstrual migraine are no different to those of women without menstrual migraine (how can it be hormones then?).¹  This has prompted one of the world’s leading authorities in this area, Professor Elizabeth Loder, to suggest that there has to be another factor in the menstrual migraine condition; ‘… an abnormal response in the central nervous system to normal fluctuations of hormones.’² i.e. the issue lies within the central nervous system.

More recently research³ has discovered exactly that – the brainstems of Menstrual Migraineurs are SENSITISED (the brainstem filters information from structures inside the head, this information then travels to the cortex, which is that part of the brain responsible for interpreting what is happening in our bodies).  Hormonal changes trigger activity (subtle expansion and contraction) of blood vessels within the head⁴ – this activity is normal and occurs (around Day 1 AND mid-cycle) for every woman.  However, there is virtual exaggeration of this increased, normal activity as it passes through a sensitised brainstem on the way to the cortex.  The cortex receives this magnified or exaggerated activity and interprets this as harmful and the response is to warn the body i.e. head pain.

Perhaps it is easier if we consider the brainstem to be an audio speaker, and a sensitised brainstem is an audio speaker with the volume control turned up.  When there is increased activity (subtle expansion and contraction) or ‘noise’ of the blood vessels, this is amplified to a level equal to shouting at the cortex… and we know what it’s like to be shouted at!

Why Triptan Medication is Effective in Menstrual Migraine

This is why the ‘triptans’, medication developed specifically for migraine are effective in relieving Menstrual Migraine^5,6 – the triptans DE-sensitise the brainstem^7,8 – they don’t change hormonal levels!  But of course this is only temporary because the triptans do not address the reason for sensitisation; surely the best approach is to identify the reason for sensitisation of the brainstem and eliminate it.

Elementary Neuro Anatomy

Elementary neuro anatomy demonstrates a relationship between the upper neck and the brainstem; information from neck muscles, joints, and ligaments are potential sources of sensitisation of the brainstem.  This possibility is strengthened by clinical experience which has included consulting women in their mid 30s (at a time when hormonal levels are stable) who developed Menstrual Migraine within 2-3 months of a neck injury.

My own PhD research⁹ has demonstrated that manual cervical intervention De-sensitises the brainstem in migraineurs – mimicking the de-sensitising effect of the triptans. (contemporary research has shown that the brainstems in migraine^10-14 and tension headache patients^15,16 are sensitised)

If menstrual migraine is unilateral, then hormones cannot be the issue. Furthermore, if a unilateral headache alternates, either within or between episodes this confirms cervical afferents as the genesis of headache.  In addition, temporary reproduction and resolution (as the examination technique is sustained) of accustomed head pain provides additional corroboration of cervical afferent relevancy.

References:

1. Macgregor EA. Female sex hormones and migraine. Rev Neurol (Paris) 2005 Jul; 161(6-7):677-8.
2. Loder E. Menstrual migraine. Curr Treat Options Neurol 2001 Mar;3(2):189-200
3. Varlibas A, Erdemoglu Ak. Altered trigeminal system excitability in menstrual migraine patients. The Journal of Headache and Pain 2009; 10(4):277-282
4. Geary GG, Krause DN, Duckles SP. Estrogen reduces myogenic tone through a nitric oxide-dependent mechanism in rat cerebral arteries. Am J Physiol 1998 Jul;275(1 Pt 2):H292-300
5. Solbach MP, Waymer RS. Treatment of menstruation-associated migraine headache with subcutaneous sumatriptan. Obstet Gynecol 1993;82(5):769-72
6. Mannix LK, Files JA. The use of triptans in the management of menstrual migraine. CNS Drugs 2005;19(11): 951-72
7. Hoskin KL, Kaube H, Goadsby PJ. Sumatriptan can inhibit trigeminal afferents by an exclusively neural mechanism. Brain1996; 119:1419-2
8. Goadsby PJ, Hoskin KL Serotonin inhibits trigeminal nucleus activity evoked by craniovascular stimulation through a 5HT1/1D receptor: a central action in migraine?Ann Neurol1998; 43: 711–8.
9. Watson DH, Drummond PD. Cervical Referral of Head Pain in Migraineurs: Effects on the Nociceptive Blink Reflex. Headache 2014;54:1035-1045
10. Katsavara Z, Lehnerdt G, Duda B, Ellrich J, Diener HC, Kaube H. Sensitization of trigeminal nociception specific for migraine but not pain of sinusitis. Neurology 2002; 59:1450-1453
11. Kaube H, Katasavara Z, Przywara S, Drepper J, Ellrich J, Diener HC. Acute migraine headache. Possible sensitization of neurons in the spinal trigeminal nucleus? Neurology 2002; 58:1234-1238
12. Katsavara Z, Giffin N, Diener HC, Kaube H. Abnormal habituation of ‘nociceptive’ blink reflex in migraine – evidence for increased excitability of trigeminal nociception. Cephalalgia 2003; 23:814-819
13. Sandrini G, Cecchini AB, Milanov I, Tassorelli C, Buzzi MG, Nappi G. Electrophysiological evidence for trigeminal neuron sensitisation in patients with migraine. Neurosci Lett 2002; 317:135-138
14. Weiller C, May A, Limmroth V, Jüptner M, Kaube H, Schayck RV, Coenen HH, Diener HC. Brain stem activation in spontaneous human migraine attacks. Nat Med 1995 Jul;1(7):658-60
15. Nardone R, Tezzon F. The trigemino-cervical reflex in tension-type headache. European Journal of Neurology 2003; 10(3):307-312
16. Milanov I, Bogdanova D. Trigemino-cervical reflex in patients with headache. Cephalalgia 2003; 23:35-38