Characteristics of female patients with migraine attacks associated with sex hormone fluctuations

The incidence and prevalence of migraine is 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. Thus, sex hormonal conditions are
known to affect the susceptibility for migraine attacks in women, but there is
a lack of understanding of the underlying pathophysiological mechanism.

Primary objective:
To compare migraine attack duration between menstrually-related migraine
attacks and non-menstrually-related migraine attacks.

Additional objectives:
- To compare clinical characteristics between menstrually-related migraine
attacks and non-menstrually-related migraine attacks.
- To compare hormone-related characteristics between menstrual cycles in which
a menstrually-related migraine attack occurred and menstrual cycles in which a
menstrually-related migraine attack did not occur.
- To compare clinical characteristics between patients with current menstrual
migraine and current non-menstrual migraine.
- To compare hormone-related characteristics between patients with current
menstrual migraine and current non-menstrual migraine.
- To compare depression and anxiety symptoms between patients with current
menstrual migraine and current non-menstrual migraine.

See for definitions on clinical characteristics of migraine attacks,
hormone-related characteristics and clinical characteristics of migraine
patients "secondary study parameters".

Definition of current menstrual migraine: migraine attacks occur on day 1 ± 2
of menstruation in at least 2 out of 3 menstrual cycles based on the
prospective diary of 3 menstrual cycles. Includes: pure menstrual migraine
without aura, pure menstrual migraine with aura, menstrually-related migraine
without aura, menstrually-related migraine with aura.

Definition of current non-menstrual migraine: no migraine attacks occur on day
1 ± 2 of menstruation in at least 2 out of 3 menstrual cycles based on the
prospective diary of 3 menstrual cycles. Includes: non-menstrual migraine
without aura and non-menstrual migraine with aura.

We will prospectively study on a daily basis female migraine patients during
three subsequent menstrual cycles. Participants will fill out a diary until the
onset of the fourth menstruation with a maximum of 105 days. A key feature will
be the implementation of modern data recording (web-based smart phone app).
This new technology will facilitate the real-time capture of migraine
characteristics, greatly improving the sensitivity and accuracy of the
information collected. Migraine patients, at least 18 years of age but not
postmenopausal and not using continuous sex hormonal therapy, are recruited via
the Headache clinic of LUMC and existing research databases, e.g. the Leiden
University Medical Centre Migraine Neuro Analysis programme (LUMINA) database
(P12.201). After written informed consent is obtained patients will provide
input on a daily basis during three subsequent menstrual cycles, with a maximum
of 105 days, about the timing of their migraine attacks and the
characteristics, e.g. accompanying symptomatology including aura symptoms,
duration and severity of attacks, use of acute and prophylactic migraine
treatments, menstrual cycle status, premenstrual complaints and exogenous sex
hormone use. In addition, participants are asked to fill out two electronic
questionnaires on severity of headache symptoms, impact on daily life,
depression and anxiety symptoms, menstrual cycle history, climacteric symptoms,
obstetric history and history of exogenous sex hormone use. One of these
questionnaires only applies to participants who are recruited through the
LUMINA database and have not already completed this questionnaire during the
last 6 months.
Based on these data obtained from a large number of patients (approximately 500
female migraine patients with a full data set), we will determine which
characteristics of female migraine patients are likely to predict the presence
of an important role for sex hormone fluctuations in the provocation of
migraine attacks.

Participation does not hold benefits for the participants. Although some
questionnaires might be confronting for patients we strongly believe this is
outweighed by the advantages.

The burden of participation will consist of:
- Filling out the electronic LUMINA questionnaire on severity of headache
symptoms, impact on daily life, depression and anxiety symptoms (time * 40-50
minutes). This questionnaire only applies to participants who have not already
completed this questionnaire during the last 6 months.
- Filling out an electronic questionnaire on menstrual cycle history, history
of climacteric symptoms, obstetric history and history of exogenous sex hormone
use (time * 30 minutes).
- Filling out an electronic diary during three subsequent menstrual cycles on
the occurrence of migraine attacks and characteristics, e.g. accompanying
symptomatology including aura symptoms, duration and severity of attacks, use
of acute and prophylactic migraine treatments, menstrual cycle status,
premenstrual complaints and exogenous sex hormone use (time * 5 minutes per
day). Participants will fill out this diary until the onset of the fourth
menstruation, with a maximum of 105 days.