Female Reproductive Stages and Migraine

The sizable difference in migraine prevalence between the sexes is largely attributed to hormonal differences.

Of the more than 37 million Americans who suffer from migraine, the majority are women. The estimated overall prevalence of migraine is 18% in women and 6% in men, and the rate is as high as 37% among women during the reproductive years.^1,2 The sizable difference between the sexes is largely attributed to hormonal differences.

“There are certainly relationships between migraine and hormones in women, and this is most pronounced in the fact that migraine in women often develops after they reach puberty, may worsen with menses, and change during pregnancy and again with menopause,” Mia T. Minen, MD, MPH, assistant professor of neurology and director of Headache Services at New York University Langone Medical Center in New York City, told Neurology Advisor. In fact, prevalence rates are similar in both sexes until puberty, and they increase in women after menarche.³ “It seems clear that certain hormonal changes that occur during puberty in girls, and remain throughout adulthood, are implicated in the triggering and frequency of migraine attacks in women,” said Huma U. Sheikh, MD, an assistant professor of neurology at Mount Sinai Beth Israel in New York City.

Menstruation

“Many women notice that they tend to have headaches a day or two before their monthly menstruation. This is thought to be due to the dramatic drop in estrogen prior to its onset,” Dr Sheikh told Neurology Advisor. An estimated 60% of women with migraine regularly experience menstrual migraine. Migraine without aura (MwA) occurs most frequently in the 2 days before and 3 days following the start of menstruation, and migraine attacks during this time have been found to be more severe, longer-lasting, and more treatment-resistant than attacks experienced at other points in the menstrual cycle.³ Notably, migraine with aura is not typically associated with menstruation, and even in patients who experience migraine with aura at other points in the reproductive cycle, aura rarely accompanies the attacks they experience during menstruation.

When migraine occurs exclusively during this 5-day time frame, it is called pure menstrual migraine, although this tends to affect less than 10% to 20% of women with migraine.³ More commonly, such patients have additional migraine attacks, with or without aura, throughout the menstrual cycle. Although research does not support an association between migraine and ovulation, some women do report getting headaches at that point in their cycle, Dr Sheikh noted.

Pregnancy

Likely because of increased estrogen levels, more than half of women with migraine experience fewer attacks during pregnancy, according to a review published in Current Neurology and Neuroscience Reports in April 2016.⁴ “This seems to be even more so for women with a prior history of menstrually related migraines,” said Dr Minen. “Even with this improvement, the majority of migraine patients will still suffer migraines at some point during pregnancy, and some experience worsened migraines, especially in the first trimester.”

Women with a history of migraine have a greater risk of adverse outcomes during pregnancy, including pre-eclampsia, preterm birth, ischemic stroke, acute myocardial infarction, and heart disease, and thromboembolic events, according to Dr Minen. Patients with migraine also generally have higher rates of insomnia, and this poor sleep quality is worse during pregnancy. A recent study in which  Dr Minen was a co-investigator, which was presented in 2016 at both the American Headache Society meeting and the European Headache and Migraine Trust International Congress, showed that 49.2% of patients presenting to headache clinics with suspected migraine had a positive insomnia screen.⁵

Menopause

“In perimenopause, estrogen levels are falling and may be associated with worsening in frequency and intensity of migraine,” Dr Sheikh explained. This was confirmed in a study reporting that high-frequency headache was increased in perimenopausal women compared with premenopausal women.⁶ “This tends to level out after menopause; around two-thirds of post-menopausal women notice an improvement in their headaches,” she said.

Treatment Considerations

If women with menstrual migraines, whether pure or not, are able to “predict when they are going to have their menses, and thus when they are going to get their migraines, we may offer ‘mini-prophylaxis treatments’ to try to prevent the migraines” said Dr Minen. This strategy may include treatment with nonsteroidal anti-inflammatory (NSAID) agents, estrogen supplementation, triptans, or magnesium.⁷ “For women with migraine who have 4 or more headache days a month, we may offer a daily preventive medication to take in addition to an abortive medication to treat the acute attack,” she added.

In weighing migraine treatment options for women in different reproductive stages, it is important to consider any other medical issues that may be present, advised Dr Sheikh. For example, when “treating pregnant women or women in their reproductive age, the risk of medications to the fetus is of the utmost importance,” she emphasized. Recent evidence suggests that several migraine therapies, including magnesium, acetaminophen, ondansetron, and butalbital may be less safe during pregnancy than previously believed and should be used with caution.⁴

“It is also important to note that although hormones play a role in triggering headaches, they may not always be the way to treat headaches, since hormones themselves can have adverse effects,” Dr Sheikh noted. For example, some evidence suggests that estrogen can increase stroke risk, and hormonal treatment — including combined oral contraceptives — is typically contraindicated in women who have migraine with aura.²

From puberty to menopause, women have an elevated risk of migraine. This requires vigilance on the part of the clinician in order to optimize treatment and minimize risks throughout the hormonal fluctuations that occur in women at the various stages of life.

References

1. Peterlin, BL, Gupta S, Ward TN, MacGregor Sex matters: evaluating sex and gender in migraine and headache research. Headache. 2011;51(6): 839-842.\
2. Edlow AG, Bartz D. Hormonal contraceptive options for women with headache: a review of the evidence. Rev Obstet Gynecol.2010;3(2):55-65.
3. Sacco S, RicciS, Degan D, Carolei Migraine in women: the role of hormones and their impact on vascular diseases. J Headache Pain. 2012;13(3):177-189.
4. Wells RE, Turner DP, Lee M, Bishop L, Strauss L. Managing migraine during pregnancy and lactation. Curr Neurol Neurosci Rep.2016;16(4):40.
5. Begasse de Dhaem O, Seng EK, Minen MT. Characterization of sleep disturbances in headache clinic patients with migraine-like headaches (abstract PS56 of “Abstracts from the 58th Annual Scientific Meeting American Headache Society”) [published online June 6, 2016]. Headache. doi:10.1111/head.12832
6. Martin VT, Pavlovic J, Fanning KM, Buse DC, Reed ML, Lipton RB. Perimenopause and menopause are associated with high frequency headache in women with migraine: results of the American Migraine Prevalence and Prevention Study. Headache.2016;56(2):292-305.
7. Tepper DE. Headache toolbox: menstrual migraine. Headache. 2014;54(2):403-408.