Hormones and Migraine:
A Lifelong Connection

By Jelena Pavlovic, MD, PhD, Assistant Professor of Neurology at Albert Einstein College of Medicine, Attending Neurologist at Montefiore Headache Center, and SWHR Migraine Network member

For women with migraine, fluctuating hormonal levels both during their monthly menstrual cycle and over the course of their lifespan are intimately connected to their experience with migraine.

Female sex hormones are thought to play a large role in the development of migraine, and hormonal fluctuations are a common migraine trigger for women. Unraveling the complex relationship between hormones and migraine will provide a better understanding of the clear sex and gender differences observed in this disease. The most obvious of these differences is that migraine is three times more common in women than men. Women are also more likely to experience longer migraine attacks and report more migraine-associated symptoms and comorbid conditions.

Women go through changes in their migraine experience over their lifespan as their hormones fluctuate during puberty, peak reproductive years, pregnancy and lactation, and the transition to menopause.

Puberty

Migraine is slightly more prevalent in boys during childhood, but this changes after the onset of puberty. At that point, migraine becomes more prevalent in women and remains such for the majority of the lifespan, suggesting a relationship between the development of migraine and periods of hormonal fluctuation such as those caused by a woman’s monthly menstrual cycle.

For example, a longitudinal study of young women revealed a link between migraine onset and the age at which a woman gets her first menstrual cycle. Each year-delay of the onset of a young woman’s first period resulted in a 7% decreased likelihood of developing migraine.

For teenagers with migraine, it may be preferable to avoid medications, except for in severe cases, and instead focus on behavioral approaches, such as keeping a headache diary to determine migraine triggers and then avoiding those triggers. If medication is necessary, doctors may prescribe triptans, the most common pharmacological treatment for relieving attacks once they occur. NSAIDs (nonsteroidal anti-inflammatory drugs) and other over-the-counter medicines can also be used. Special care should be taken with caffeine-containing compounds in this age group, as caffeine has a very complex relationship with migraine and caffeine-containing compounds may contribute to chronic migraine in some people.

Peak Reproductive Years

Migraine prevalence in women peaks during their 30s and early 40s, at a time when women are balancing their growing careers, family, and social obligations. During peak prevalence, a quarter to a third of migraine patients will experience at least four attacks per month. For many women, these attacks appear to be linked to hormonal fluctuations during their monthly menstrual cycle.

Menstrual migraine is a migraine subtype defined as migraine attacks occurring in at least two of three menstrual cycles, extending from 2 days before onset of flow through 3 days after onset. It is important to keep in mind, however, that an individual woman may have a different window of peak migraine likelihood that is associated with her monthly hormonal changes. While estimates of the prevalence of pure menstrual migraine (where attacks occur exclusively around the time of menses) range from 3.5% to 12%, more than 50% of women with migraine experience menstrual-related attacks. Menstrual migraine is associated with more disability as the attacks are more severe, more resistant to treatment, and longer lasting.

During peak reproductive years, a variety of preventive and abortive therapies as well as behavioral modifications are often used. For many women, use of hormonal contraceptives can limit the hormonal fluctuations and therefore reduce migraine-related symptoms. However, women seeking to have children have more limited options since they cannot use birth control and other medications may cause birth defects. These challenges make pre-pregnancy planning particularly relevant in women with migraine.

Pregnancy

Pregnancy usually lessens both the frequency and severity of women’s migraine attacks, which may be due to the steady increase in estrogen during each trimester. In one study, about two-thirds of women had fewer migraine attacks during pregnancy, particularly in the second and third trimesters. Another study showed that by the third trimester 89% of women had either no attacks or fewer attacks. On the other hand, a minority of women experience their first migraine attack during pregnancy, usually during the first trimester.

After delivery, women’s estrogen sharply declines, which may explain why almost all women report the return of migraine attacks after giving birth. However, research has found that women who breastfeed experience a lower incidence of migraine attacks post-delivery, likely because estrogen levels remain higher in these women.

Due to limited data on many pharmacological migraine treatments during pregnancy and breastfeeding, women are generally advised to rely upon behavioral and healthy lifestyle recommendations for migraine relief during this time.

Menopausal Transition

A woman’s hormones fluctuate dramatically during the menopausal transition (usually starting in mid-40s and continuing into the 50s) and migraine attacks tend to increase in frequency as a consequence of these hormonal fluctuations. Occasionally, migraine attacks may worsen significantly in this period, leading women who previously have not sought treatment to pursue medical care and get officially diagnosed. During this stage, another treatment option for migraine is hormone replacement therapy, which is used to treat menopausal symptoms like hot flashes and works by stabilizing hormonal levels.

Estrogen levels decline post-menopause, as do the prevalence of migraine attacks. One study reported about two-thirds of post-menopausal women with migraine showed improvement. At this time, many women who need to pursue pharmacological migraine treatment options may need to take into consideration cardiovascular risk factors and drug-drug interactions. This is where the brand-new class of migraine drugs, calcitonin gene-related peptide (CGRP) inhibitors, offer a lot of promise.

Future Research on Hormones and Migraine

Researchers now understand that hormonal shifts may be key to identifying differences among those who experience migraine. However, there is a lack of large longitudinal studies that simultaneously capture hormonal and migraine data, which are needed to fully grasp the connection between hormones and migraine.

The Society for Women’s Health Research recently published a report in the Journal of Women’s Health that summarizes current research on sex and gender differences in migraine based on a roundtable discussion hosted by SWHR with expert researchers, clinicians, and patients. The report identifies priority research areas in migraine that warrant further attention, including the need for more studies that look at hormonal influences on migraine.