The Migraine- WHAT! Study (Women, Hormones, Attacks and Treatment)

Migraine is a prevalent episodic brain brain disorder, affecting three times more women than men. The disease is typically characterised by disabling recurring attacks of severe headaches and associated neurological features. WHO ranks migraine as the seventh most disabling disease overall and third among women. With women’s increased participation in the labour force migraine may not only cause disability but also hamper career development for women. Whereas migraine is a multifactorial disease involving several factors such as, e.g., genetic predisposition, in women the occurrence of migraine attacks is highly related to hormonal changes such as during menarche, pregnancy, menopause or menstruation, making a prominent role for sex hormones likely. We have chosen to specifically investigate the role of female sex hormones in the pathophysiology of migraine since evidence on mechanisms involved is limited [1]. A recent study suggested that, in the late luteal phase of the menstrual cycle, female migraine patients have a more rapid decline in estradiol compared to healthy women [2,3]. However, the relationship with occurrence of migraine attacks was not clear. Besides, there is knowledge on neither other sex hormones, nor on changes over lifetime of the sex hormones in female migraine patients. Most importantly, it is not clear how to change sex hormones levels to prevent attacks although some small studies suggested that oral contraceptives might be protective in women with menstrually-related migraine. Finally, migraine women have an increased cardiovascular risk and oral contraceptives increase this relative risk but especially when women also smoke. Thus, it is also crucial to study how sex hormones affect the vascular function in women with migraine. This knowledge may be important when treating migraine women with oral contraceptives. We hypothesise that migraine attacks in females are triggered by changes in sex hormones. Our ambition is: i) to unravel the role of sex hormones in the provocation of migraine attacks; ii) to develop targeted preventive strategies for migraine attacks in female migraine patients; iii) to unravel how sex hormones affect vascular reactivity in women with migraine. For this we set up five projects to investigate: 1) which characteristics of female migraine patients are likely to affect outcomes; 2) the role of sex hormones in provoking menstrually-related migraine attacks; 3) the role of sex hormones in provoking migraine during perimenopause; 4) hormonal treatment in female migraine patients; 5) how sex hormones affect vascular reactivity. We can make a major contribution to the area of migraine prevention in women as we have unique access to large well-characterised migraine patient populations, state-of-the-art methods to measure sex hormones and vascular reactivity, and a unique collaboration with world leading experts in the fields of migraine and female sex-hormones.