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Role of female sex hormones in migraine

The incidence and prevalence of migraine are three times higher in women than in men. Clinical and epidemiological studies suggest a prominent role for sex hormones in female migraine patients. Menstruation is an important factor increasing the susceptibility for an upcoming attack. Hormonal fluctuations during menopausal transition are also associated with increased susceptibility for migraine. In contrast, pregnancy, lactation and postmenopausal status are associated with an improvement in migraine. Furthermore, migraine attacks during menstruation are known to be more severe, longer lasting and more difficult to treat. Currently, there is no evidence-based method to intervene with sex hormones for the treatment of migraine in women.

The study

WHAT stands for “Women, Hormones, Attacks and Treatment”. The study comprises three parts. The ultimate goal of The Migraine WHAT! – Study is to unravel the pathophysiological role of sex hormonal fluctuations in the provocation of migraine attacks and to find an effective hormone-based treatment for female migraine patients.

Part 1: Headache and menstruation diary

The first part of the study focusses on women with migraine with a (regular) menstrual cycle. Participants register headache symptoms and symptoms related to the menstruation in a daily e-diary over a period of approximately three months. After completion of part one, we hope to be able to predict in which women sex hormonal changes play an important role in the provocation of migraine attacks.

Part 2: Hormone regulation

In part two we will focus on women with migraine attacks during menstruation or perimenopause. We will measure sex hormones in blood, urine and saliva at different time points during the menstrual cycle to improve our understanding of the sex hormone regulation in women with migraine.

Part 3: Hormonal treatment

In part three we will also focus on women with migraine attacks during menstruation or perimenopause. There is a great need for better prophylactic treatment among women with migraine. A lot of women use hormonal treatments like the oral contraceptive pill as prophylactic therapy. However there is insufficient evidence supporting the efficacy of these drugs. Part three, therefore, comprises two clinical trials to investigate the effect of the continuous use of contraceptive pills in women with migraine.

For more information about our headache research see For more information about the LUMC headache clinic see


To enrol in one of our WHAT! studies sufficient mastery of the Dutch language is required. Additional information on enrolment is accessible through the Dutch version of this web page. It is also necessary for participants to live in the Netherlands and have a Dutch health insurance.

The WHAT study is subsidized by ZonMw and the Hersenstichting.