New Italian research links migraine and endometriosis

Research published today (Thursday 28 October) in Europe’s leading reproductive medicine journal Human Reproduction[1] , has found evidence that women with endometriosis[2] are at higher risk of having migraine.


A team from the University of Genoa in Italy studied 133 women with endometriosis and a control group of 166 women, and found that the prevalence of migraine was significantly higher among the women with endometriosis. Double the number of women in the endometriosis group had migraine compared with the controls.

Although more women with endometriosis had migraine there was no evidence that they had more frequent attacks or more intense pain than the control women who had migraine, and there was no link either with the severity of the endometriosis. However, the researchers did find that age of onset of the migraine was lower in the endometriosis group – 16.4 years as opposed to 21.9.

The study, led by Dr Simone Ferrero, a research fellow and a specialist registrar at the Gynaecologic Department of the University of Genoa, involved women of reproductive age who were undergoing laparoscopy because of infertility, ovarian cysts, benign uterine tumours or pelvic pain. All the women who indicated that they had had at least one headache in the past year were referred to a specialist headache neurologist who performed a clinical interview and classified their headaches according to internationally accepted criteria.

Said Dr Ferrero: “In our population of women with endometriosis a third of the women suffered migraine (and over 13% experienced aura before the onset of the headache), which was significantly higher than we observed in the control group where only 15% suffered from migraine. Although we can’t rule out recall bias, the women with endometriosis reported a lower age at onset than the controls. But, our results did indicate that migraine severity was similar in women with and without endometriosis and was not related to the severity of the endometriosis either.”

He said that an estimated 5% of women of reproductive age have endometriosis and somewhere between 15% and 19% of this age group in Europe and the USA have migraine. “In the light of the findings of the study, the two conditions together would be likely to affect around 2 in every 100 women of reproductive age.”

The findings did raise some problems and concerns, Dr Ferrero said. “Women with migraine often do not seek appropriate care: for example, it has been reported that more than 4 in 5 patients who consult a physician about their headaches do not see a neurologist or headache specialist. Instead, they consult their primary care practitioner, which, for many women is their gynaecologist. In our study just over 27% of the women with endometriosis and 24% of the control patients had seen a headache specialist and this low rate of migraine assessment had resulted in low rates of specific treatment.”

Dr Ferrero said that a gynaecologist must investigate headache carefully in all women with endometriosis but that headache classification should always be performed by a neurologist experienced in diagnosing migraine. “I believe all gynaecologists should always ask their patients with known or suspected endometriosis, ’do you suffer from headaches’? If they do, then a consultation with a neurologist should be advised. When endometriosis and migraine exist together each exerts a significant and independent negative effect on a woman’s quality of life, and pain and the associated symptoms of migraine can be greatly reduced with adequate diagnosis and treatment.”

Dr Ferrero said that migraine, particularly migraine with aura, was known to be an independent risk factor for ischaemic stroke in women of reproductive age. Although the absolute risk of stroke was extremely low, it was important that women with endometriosis receiving hormonal treatments should have migraine investigated and diagnosed by a headache specialist as it may be prudent to change the treatment if the migraine developed, or increased, after hormone treatment started. For women needing contraception, combined injectable contraceptives, vaginal rings or progestin-only contraceptives should be the methods considered.

“We don’t really understand the link between the two conditions although some biochemical mediators have been implicated. It is possible that systemic spreading of prostaglandins produced by endometriosis may contribute to migraine and it has also been shown that upregulation or disregulation of nitric oxide synthesis has a role in both migraine and endometriosis. But the association between the two conditions requires further research.”

[1] Increased frequency of migraine among women with endometriosis. Human Reproduction.
Doi: 10.1093/humnrep/deh537.

[2] Endometriosis is a painful and distressing condition in which endometrial tissue that under normal circumstances is found only in the lining of the womb, develops outside the uterus and attaches itself to ligaments and organs in the abdominal cavity. This tissue responds to the menstrual cycle as though it were still inside the uterus. The repeated growth and disintegration of endometrial tissue in the abdomen can cause bleeding, pain, inflammation, adhesions and infertility.

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