Hormones and Migraine Research

By virtue of the specific research undertaken at the City of London Migraine Clinic, we are able to offer our expertise in the management of migraine in women.
Specific research undertaken on hormones and migraine includes:

Migraine and menstruation
Diary card data from 55 women who had complete data of migraine and menstruation for 3 complete cycles was analysed to determine the association between migraine and menstruation. Menstruation was associated with migraine for the majority of women but for a minority, the association was exclusive. A definition for 'menstrual' migraine was developed of attacks of migraine without aura occurring exclusively on days 1±2 of the cycle, which has implications for hormonal prophylaxis.
Publication: MacGregor EA, Chia H, Vohrah RC, Wilkinson M. Migraine and menstruation: a pilot study. Cephalalgia 1990; 10: 305-10.

Headaches and Hormones – subjective versus objective assessment
A comparison of questionnaire responses versus diary card evidence of the association between migraine and menstruation in 100 women with migraine. The results have important implications for clinical practice as they show that more women report as association between migraine and menstruation than is evidenced by diary cards (51 per cent versus 15 per cent). It was concluded that 'menstrual' migraine should not be treated as such until the diagnosis is confirmed with prospective diary records.
Publication: MacGregor EA, Igarashi H, Wilkinson M. Headaches and Hormones: Subjective versus objective assessment. Headache Quarterly 1997; 8: 126-36.

Headaches and migraine in a specialist menopause clinic
The clinical impression of migraine as a menopausal symptom was confirmed in this study of 74 women attending a specialist menopause clinic. Although 29% were identified with migraine in the preceding 3 months, few complained of headache as a specific symptom. The results have important implications for those treating women with menopausal symptoms, who should ask specifically about headache and migraine.
Publication: MacGregor EA, Barnes DS. Migraine in a specialist menopause clinic. Climacteric 1999; 2: 218-23.

Effect of different types of HRT on migraine
This was a questionnaire of members of Migraine Action Association undertaken to study the subjective effects of different types of HRT. The results from 112 completed questionnaires suggested that oral oestrogens were associated with deterioration of migraine and non-oral routes were associated with improvement. This preliminary study refutes the myth that HRT should not be given to women with migraine, but suggests that routes of delivery associated with minimal oestrogen fluctuations, such as patches or gel, can have a favourable effect.
Publication: MacGregor EA. Effects of oral and transdermal estrogen replacement on migraine. Cephalalgia 1999; 19: 124-5.

Oestrogen as a trigger for migraine aura
While prescribing HRT to migraineurs, it was noted that some women developed migraine aura, de novo, which disappeared with a dose reduction of oestrogen. Four of these women were presented as case reports in order to alert other researchers of this association. This finding has important clinical implications as migraine with aura has been associated with increased risk of ischaemic stroke, a condition which natural oestrogens have been considered to prevent.
Publicaton: MacGregor EA. Estrogen replacement: a trigger for migraine aura? Headache 1999; 39: 674-8.

The effect of natural oestrogen supplements on migraine during the pill free week of combined oral contraception
Migraine during the pill-free week of combined oral contraception is common in clinical practice but management has always been empirical. The mechanism is thought to be 'oestrogen-withdrawal', as for menstrual migraine. The results of this pilot study on 14 women suggest that use of 50 mcg oestrogen patches during the pill-free interval may reduce the frequency and severity of migraine at that time. This study should be repeated with larger numbers of women and a higher dose of oestrogen.
Publication: MacGregor EA, Hackshaw A. Prevention of migraine in the pill-free week of combined oral contraceptives using natural oestrogen supplements. J Family Planning and Reproductive Healthcare 2025; 28(1):27-31

Differences between migraine attacks related to menses and non-menstrual attacks - symptoms, duration.
This study aimed to determine if migraine was more likely to be associated with menstruation compared to other times of the menstrual cycle in female migraineurs, and whether such migraines tend to be more severe and associated with vomiting, nausea or aura. The analysis was based on 155 women with diaries completed for at least 2 consecutive menstrual cycles. 17% provided data for 2 cycles, 37% for 3 cycles, 16% for 4 cycles and 30% for 5 or more cycles. On average, women were 1.7 times more likely to have a migraine during the 2 days before menstruation and 2.5 times more likely on and the 2 days after menstruation. Migraine attacks were more severe just before and just after menstruation. Women were 2.1 times more likely to have a severe migraine during the 2 days before menstruation and 3.4 times more likely during the 2 days after menstruation.

Publication in preparation
A study of the association between oestrogen withdrawal and 'menstrual' migraine and the prevention of such attacks by optimal timing in a double blind placebo controlled study of natural oestrogen supplements used optimally to prevent oestrogen withdrawal during the late luteal phase of the normal menstrual cycle
This study was undertaken to record prospectively the association between migraine and oestrogen levels at different phases of the menstrual cycle, and to identify the optimal time for use of oestrogen supplements. 40 women with confirmed menstrual or menstrually-related migraine were invited to keep diary cards and collect an early morning urine sample for three months. This was followed by a further 6 month double-blind randomised placebo–controlled study using oestradiol supplements in the late-luteal phase of the menstrual cycle (3 cycles oestradiol, 3 cycles placebo). The results support the hypothesis that migraine is associated with oestrogen ‘withdrawal’ as there was a significant increase in migraine in the late luteal phase in the pre-treatment cycles in association with falling levels of oestrogen. Oestradiol gel significantly reduced migraine days and migraine severity in the late luteal phase, compared to placebo.

Publication in preparation
We hope to continue with many further studies assessing the association between migraine and hormones, including the effects of different methods of contraception on migraine and the effect of hormones on the risk of ischaemic stroke in women with migraine.