A man is talking to the viewer, but his face is partially obscured by a blur and streaks of color.
I can’t fall asleep. Can’t stay awake. I can’t close my eyes but I can’t leave them open. I can’t eat and I can’t drink, yet my stomach rumbles and my throat is dry. Can’t lie down, can’t sit up, can’t stand. The lights are off and the curtains are drawn shut. I stare into the dark expanse of my ceiling. I’m missing class; there’s so much homework I need to catch up on. It hurts.
I can’t describe the feeling of migraine in a simple and straightforward way because everyone experiences migraine differently. For Dr. Mariam Aly, Assistant Professor of Psychology at Columbia University, it’s the feeling of your head being slowly crushed by a vise. For my mother, it’s the feeling of all of your body, all of your pain, being forced in your skull. And for me, migraine is an endless series of “can’t.” I can’t do anything, except wait for it to end.
When I’m asked about my migraine, here’s how I define it: “a bunch of bad headaches, pretty often, but I’m used to it!” At least, that’s my response when I’m in conversation with acquaintances who might sympathize but not empathize, or when I want to pivot to any other topic of conversation. A more accurate (and scientific) definition would be this: migraine is a neurological disease that is characterized by intense, throbbing, and recurrent pain on one side of the head, and the term “migraine attack” refers to an individual instance of head pain [1]. Usually, migraine attacks are triggered by certain internal and external stimuli, including stress, changes in sleep, hormonal changes, weather changes, and a variety of sensory stimuli, such as flashing lights or loud sounds [2, 3, 4, 5]. An untreated migraine attack can last anywhere from four to 72 hours, and is accompanied by a slew of other nasty symptoms such as nausea, vomiting, fatigue, irritability, and sensitivity to light and sound [1, 6]. Up to 31 percent of patients with migraine also experience aura, or sensory disturbances, which serves as a sort of “warning system” prior to the migraine attack [7]. Aura typically manifests as visual or sensory symptoms, such as seeing blind spots or feeling tingling in one’s fingers, which emerge and are resolved before the onset of head pain [6].
However, there’s an aspect of migraine that seldom comes up in a short fact-filled paragraph summary: it’s a disease that predominantly affects those assigned female at birth, hereafter referred to as “female” [8]. In fact, according to the number of medical diagnoses, migraine impacts between two to three times as many females as it does those assigned male at birth, hereafter referred to as “male” [8]. With this statistic in mind, scientists have conducted research acknowledging the possibility that sex differences affect rates of migraine.
Sex Differences in Migraine
The occurrence of migraine attacks in females fluctuates throughout their lifetimes. While migraine tends to be less frequent in children than in adults, young females and young males are equally likely to develop migraine [9]. However, as children grow up, there seems to be a shift. With the onset of puberty, females begin to show an increase in migraine prevalence as compared to males, resulting again in that ratio falling between two to one and three to one [8]. These rates hold up for the majority of adulthood [8]. Yet after menopause, which generally begins in mid-life, there’s another shift: the majority of females who have migraine see an improvement in the severity and the frequency of their condition [10]. So, the rates of migraine ebb and flow throughout a female’s lifetime. Why?
One possible and prevalent theory for the sex differences in migraine is the fluctuation of estrogen levels in females due to their menstrual cycle. This explanation has been around for a while. In 1972, Australian clinician Dr. Brian Somerville studied the influence of female sex hormones on females with migraine and found a correlation between the shift in female sex hormones and the rate of migraine attacks [11]. The menstrual cycle is associated with a cyclical variation in female sex hormones such as estrogen [12]. And, while the exact rates vary from person to person, the frequency of migraine attacks tends to be higher in the two days before and three days after the onset of menstruation, when estrogen levels suddenly drop from their previously high levels [13, 14]. Over 55 percent of females have migraine attacks related to their menstrual cycle, and rates of migraine actually lower during pregnancy [15]. After menopause, however, estrogen levels stabilize, and migraine rates and symptoms improve [10]. If postmenopausal females choose to undergo hormonal replacement therapy—especially therapies that contain estrogen—their migraine tends to worsen [16]. Overall, there appears to be a strong link between sex hormones and migraine, with fluctuating levels of estrogen correlating with migraine attacks.
An anonymous hand is turning on a singular light bulb
in a dark room in front of some curtains.
Another theory takes a different approach to how female sex hormones might have an effect on migraine and migraine attacks. Nasim Maleki, assistant professor of psychiatry at the Massachusetts General Hospital, concludes that hormonal fluctuation might serve as a trigger for migraine attacks rather than as a cause for migraine [17]. Maleki found structural and functional differences in the brains of females with migraine versus the brains of males with migraine [18]. For example, one key difference was that the left posterior insula, a region of the brain involved in pain perception, was thicker in females with migraine than males with migraine and controls groups of both sexes [18]. While the reason for this difference in thickness is unknown, a thicker left posterior insula potentially relates to higher pain levels reported by females with migraine as compared to males with migraine [18, 19]. With this and numerous other findings, Maleki hypothesizes that differences in brain structure and development might be the framework for what causes an individual to develop migraine as a disease [18]. Subsequently, hormonal fluctuation could be the tipping point for an individual migraine attack—just like how light, sound, environmental factors, and other physical and emotional stimuli can elicit migraine attacks [6].
The administration of certain sex hormones also alters the rates of migraine attacks in transgender people. While the data is extremely limited, a survey conducted in 2004 found similar rates of migraine attacks between cisgender women and transgender women who have undergone hormone therapy involving estrogen dosing [20]. In contrast, transgender men who take testosterone have lower rates of migraine attacks when compared to cis women [17]. Although this topic still needs further study, cisgender men with chronic migraine have also been noted to have lower than average total testosterone levels, along with increased levels of the female sex hormone estrogen [21, 22].
Sex Differences in the Clinical Studies and Treatment of Migraine
By now, we’ve become acquainted with the current hypotheses on migraine that center on the fluctuating female sex hormones that trigger migraine attacks, along with how differences in brain function and structure might relate to migraine. We’re also familiar with the sex disparity in those who experience migraine: females and males have been diagnosed with migraine at a ratio that falls somewhere between two to one and three to one. So, we’d assume that, ideally, this ratio would carry over to the subjects of clinical studies on migraine, so that both populations are represented appropriately. Unfortunately, that isn’t the case.
Despite females being disproportionately affected by migraine, the majority of migraine research studying animals, such as rodents, has been conducted almost entirely on males [23]. This is because, in many cases, male animals are seen as more convenient to study than their female counterparts, since the reproductive cycle of female rodents is an added variable that can complicate research [24]. But this preference for male animals has consequences: nearly 80 percent of the animal studies focusing on migraine published in the research journal Pain over the span of ten years included only male subjects. Out of all of these studies, only four percent were designed to test for sex differences [24]. Males are heavily overrepresented in animal studies on migraine, which creates studies with a critical blind spot.
Interestingly, the reverse is true of human clinical trials. The sex difference in the population of people with migraine is between two females to one male and three females to one male. Yet, studies targeting structural differences in those with migraine drastically overrepresent females at a ratio of eight female subjects for every one male subject [18]. While males are overwhelmingly included in migraine studies on animals, males are severely underrepresented in migraine studies on humans [18, 23]. This underrepresentation leads to not only less public awareness that males do, in fact, suffer from migraine, but also less clinical research on how males might manifest migraine differently from females [18]. While both animal and human clinical studies of migraine disproportionately study certain sexes, neither approach represents the true population of interest, ultimately resulting in research that does not do justice to the people it aims to help.
Not only are different sexes (such as female and male) with migraine represented differently in clinical trials, but different genders (such as women and men) are also likely to be treated differently in the management of their disease. For example, women are more likely to be prescribed acute medication for treating migraine, while men typically use non-prescription medication or even no medication at all to treat migraine [25]. Additionally, compared to women, men are less likely to reach out to medical professionals for help with their migraine [25]. While it is possible that this difference in medication might suggest sex differences in migraine severity, it might also indicate a broader trend in how different genders are socialized to respond to pain and diseases. Societal pressures might therefore contribute to the underdiagnosis of migraine in men and their lack of participation and recruitment in migraine research, another contributing factor to the underrepresentation of men in human clinical trials [26].
Migraine and Society
15.9 percent of adult Americans—a little over one in every six people—are unified by migraine [27]. Yet if you look around a college campus, it’s unlikely that you’ll find that one in six ratio. A survey of people with migraine found that, of those who chose to share their educational background, only 11 to 12 percent of people with migraine (or one in eight) had completed any form of higher education, such as a bachelor’s degree [27]. From that same survey, between 35 to 40 percent of respondents from 2012 to 2018 reported that, at the time of their response, they had been unemployed for the past three months [27]. Overall, there are greater rates of migraine in groups of people with lower income and lower levels of educational attainment [28]. Additionally, those with migraine living in the lowest income bracket (less than $22,500 annually) are more likely to suffer from extremely severe pain when compared to those with migraine living in higher income brackets [28]. These statistics all support the same conclusion: the rates and severity of migraine may be related to socioeconomic status.
Two popular hypotheses link disease and socioeconomic background [28]. The first, the social selection hypothesis, argues that a disabling disease may result in an individual being unable to fulfill their educational or occupational demands. This ultimately leads to a decline in said individual’s social and economic status. On the other hand, the social causation hypothesis postulates that a low socioeconomic status, because it is associated with stress and other disease mediators such as poor nutrition, increases the risk of illnesses [28]. While these hypotheses certainly differ, they both agree on one key point: there is a strong association between illnesses such as migraine and socioeconomic background [27].
Invisible illnesses are, as their name suggests, not always apparent to the eye. People living with invisible illness, such as migraine, traumatic brain injury, or mental illness, have—in the past and to this day—faced struggles gaining recognition, accommodation, and understanding from their peers and communities. For example, we can see a broken leg; we wouldn’t tell someone with a broken leg to walk. We can relate to the stuffiness and exhaustion of the flu; we wouldn’t ask someone with a high fever to go to work (especially in these times!). But invisible illnesses, because they are not easily detected by others, often do not garner the same societal support and acknowledgment that other diseases do.
In 2011, Swedish researchers Stina Rutberg and Kerstin Öhrling interviewed ten women with migraine between the ages of 37 and 69 about how migraine has affected their daily lives [29]. When asked about their experiences, three common themes arose: feeling besieged by an attack, struggling with the uncertainty of an unpredictable disease, and living with an invisible disorder. For every woman surveyed, the invisibility of migraine was a central component—they lived with the fear of their illness and the pain of not being believed by others. The women shared that their social and professional circles viewed a debilitating migraine attack the same as a mild, yet still uncomfortable, headache. For them, migraine wasn’t an excuse to miss work or social obligations. Instead, it was just a feature of life that made living even harder; as one woman said, “you learn to live with it [migraine] and you do not know what life would be like without it” [29]. In other words, these women with migraine were pressured to push themselves in their career and social spaces, even when incapacitated by illness.
Two pairs of hands are clasped together in comfort and understanding, and the colors are warm and bright.
You might have noticed something strange about the study I just mentioned. Rutberg and Öhrling only interviewed women, not men [29]. While writing this article, I searched carefully for qualitative studies of men with migraine similar to the one conducted by Rutberg and Öhrling, but I couldn’t find anything. As I’ve mentioned many times thus far, migraine affects females and males at a ratio between two to one and three to one. However, neither I nor Professor Mariam Aly, whom I had the pleasure of interviewing in October, had ever met an adult man with migraine at the time of our discussion. In fact, I only met men with migraine very recently through the process of writing this article, resulting in my own ratio of twelve to two. That is—I know twelve women with migraine and two men with migraine.
Yet, men with migraine certainly exist. So, why don’t we know more about them? One reason could be due to the stigma associated with illness, including and especially invisible illnesses such as migraine. Imposed societal expectations of strength and invulnerability can pressure men to avoid seeking treatment for illness, leading to potentially deadly consequences [30]. I had the opportunity to talk with the two aforementioned men with migraine, who asked to remain anonymous for the purpose of this article. For them, their struggles with migraine were exacerbated by gendered expectations. With the obligation to adhere to a standard of activeness and strength as men, they were not comfortable sharing their migraine with others unless absolutely necessary. Additionally, as college students, they felt that their migraine had “become another class to take” in their schedule—that is, yet another strenuous commitment that barred them from the academic, career, and social opportunities they would otherwise love to participate in. They had to push themselves—push themselves to do more than they could physically do, push themselves beyond their sickness, push themselves beyond their limits to avoid other people seeing them as less capable because of their disease.
It Shouldn’t Hurt.
Growing up as a person with migraine, I was pressured to push myself. Burning-hot shame ate at me every time I had to write an email or shoot a text: “I’m sorry… I can’t make it today… have a headache again :( .” Sometimes it’s easier to just go to class, or practice, or work, even when it hurts. So I wouldn’t be weak. And, more importantly, so I wouldn’t be seen as weak, suffering from an illness only I could see. I had never imagined a life where it didn’t hurt. That's why, when I sat down with Professor Mariam Aly in October to speak about her migraine, I was pleasantly surprised. A year ago, Professor Aly started calcitonin gene-related peptide (CGRP) antibody injections to treat her migraine. CGRP antibodies target the neurotransmitter calcitonin gene-related peptide, which is associated with migraine attacks, and through doing so may relieve pain from migraine and even help prevent migraine attacks [31]. Although she sometimes still gets migraine attacks, her most severe ones have ceased, and her quality of life has dramatically improved. Even now, however, there are still times when she needs to teach, give research talks, or attend meetings while dealing with pain. Just like the ten women interviewed by Rutberg and Öhrling, her professional and personal obligations demand her to push herself—even when it hurts.
But it shouldn’t hurt. You shouldn’t have to go to school, you shouldn't have to go to work, and you shouldn’t have to go to a meeting when you don’t feel good. Of course, I’m aware, this is easier said than done—but it can be done. Current social movements have called for greater awareness, understanding, and accommodation of illnesses for all genders. As of 2016, the US National Institutes of Health has required researchers to consider sex as a biological variable in animal and human studies [32]. And while there’s still a lot we need to do, there’s one key principle to guide us: we deserve to feel good and healthy and happy. We can feel good and healthy and happy.
Good and healthy and happy mean different things to different people. Here’s what they mean to me: by the time this article is published, I’ll have seen my doctor to get started on preventative treatments for migraine—and, bit by bit, change a “can’t” into a “can.”
References
Goadsby, P. J., Lipton, R. B., & Ferrari, M. D. (2002). Migraine—current understanding and treatment. New England Journal of medicine, 346(4), 257-270.
Silva-Néto, R. P., Peres, M. F. P., & Valença, M. M. (2014). Odorant substances that trigger headaches in migraine patients. Cephalalgia, 34(1), 14-21.
Tekatas, A., & Mungen, B. (2013). Migraine headache triggered specifically by sunlight: report of 16 cases. European neurology, 70(5-6), 263–266.
Wang, J., Huang, Q., Li, N., Tan, G., Chen, L., & Zhou, J. (2013). Triggers of migraine and tension‐type headache in China: a clinic‐based survey. European journal of neurology, 20(4), 689-696.
Scheidt, J., Koppe, C., Rill, S., Reinel, D., Wogenstein, F., & Drescher, J. (2013). Influence of temperature changes on migraine occurrence in Germany. International journal of biometeorology, 57(4), 649-654.
Rizzoli, P., & Mullally, W. J. (2018). Headache. The American Journal of Medicine, 131(1), 17–24.
Launer LJ, Terwindt GM, Ferrari MD. The prevalence and characteristics of migraine in a population-based cohort: the GEM study. Neurology 1999;53:537-42.
Vos, T., Allen, C., Arora, M., Barber, R. M., Bhutta, Z. A., Brown, A., ... & Boufous, S. (2016). Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. The Lancet, 388(10053), 1545-1602.
Bille, B. O. (1962). Migraine in school children. Acta Paediatrica, 51(5), 614-616.
Sacco, S., Ricci, S., Degan, D., & Carolei, A. (2012). Migraine in women: the role of hormones and their impact on vascular diseases. The journal of headache and pain, 13(3), 177-189.
Somerville, B. W. The influence of progesterone and estradiol upon migraine. Headache 12, 93–102 (1972).
Thiyagarajan, D. K., Basit, H., & Jeanmonod, R. (2020). Physiology, menstrual cycle. StatPearls [Internet].
MacGregor, E. A., & Hackshaw, A. (2004). Prevalence of migraine on each day of the natural menstrual cycle. Neurology, 63(2), 351-353.
Johannes, C. B., Linet, M. S., Stewart, W. F., Celentano, D. D., Lipton, R. B., & Szklo, M. (1995). Relationship of headache to phase of the menstrual cycle among young women: a daily diary study. Neurology, 45(6), 1076-1082.
Granella, F., Sances, G., Zanferrari, C., Costa, A., Martignoni, E. and Manzoni, G.C. (1993), Migraine Without Aura and Reproductive Life Events: A Clinical Epidemiological Study in 1300 Women. Headache: The Journal of Head and Face Pain, 33: 385-389.
Facchinetti, F., Nappi, R. E., Tirelli, A., Polatti, F., & Nappi, G. (2002). Hormone supplementation differently affects migraine in postmenopausal women. Headache: The Journal of Head and Face Pain, 42(9), 924-929.
Eisenstein, M. (2020). Closing the gender gap in migraine research. Nature, 586, S16-S17.
Maleki, N., Linnman, C., Brawn, J., Burstein, R., Becerra, L., & Borsook, D. (2012). Her versus his migraine: multiple sex differences in brain function and structure. Brain, 135(8), 2546-2559.
Apkarian, A. V., Baliki, M. N., & Geha, P. Y. (2009). Towards a theory of chronic pain. Progress in neurobiology, 87(2), 81–97.
Pringsheim, T., & Gooren, L. (2004). Migraine prevalence in male to female transsexuals on hormone therapy. Neurology, 63(3), 593-594.
van Oosterhout, W. P., Schoonman, G. G., van Zwet, E. W., Dekkers, O. M., Terwindt, G. M., MaassenVanDenBrink, A., & Ferrari, M. D. (2018). Female sex hormones in men with migraine. Neurology, 91(4), e374-e381.
Shields, L. B., Seifert, T., Shelton, B. J., & Plato, B. (2019). Testosterone levels in men with chronic migraine. Neurology international, 11(2), 18-20.
Peterlin, B. L., Gupta, S., Ward, T. N., & MacGregor, A. (2011). Sex matters: evaluating sex and gender in migraine and headache research.
Mogil, J. S., & Chanda, M. L. (2005). The case for the inclusion of female subjects in basic science studies of pain. Pain, 117(1-2), 1–5.
Buse, D. C., Loder, E. W., Gorman, J. A., Stewart, W. F., Reed, M. L., Fanning, K. M., Serrano, D., & Lipton, R. B. (2013). Sex differences in the prevalence, symptoms, and associated features of migraine, probable migraine and other severe headache: results of the American Migraine Prevalence and Prevention (AMPP) Study. Headache, 53(8), 1278–1299.
Vetvik, K. G., & MacGregor, E. A. (2017). Sex differences in the epidemiology, clinical features, and pathophysiology of migraine. The Lancet Neurology, 16(1), 76-87.
Burch, R., Rizzoli, P., & Loder, E. (2018). The prevalence and impact of migraine and severe headache in the United States: figures and trends from government health studies. Headache: The Journal of Head and Face Pain, 58(4), 496-505.
Stewart, W. F., Roy, J., & Lipton, R. B. (2013). Migraine prevalence, socioeconomic status, and social causation. Neurology, 81(11), 948-955.
Rutberg, S., & Öhrling, K. (2012). Migraine–more than a headache: Women’s experiences of living with migraine. Disability and rehabilitation, 34(4), 329-336.
Chatmon B. N. (2020). Males and Mental Health Stigma. American journal of men's health, 14(4), 1557988320949322.
Edvinsson, L., Haanes, K. A., Warfvinge, K., & Krause, D. N. (2018). CGRP as the target of new migraine therapies—successful translation from bench to clinic. Nature Reviews Neurology, 14(6), 338-350.
U.S. Department of Health and Human Services. (n.d.). NIH policy on sex as a biological variable. National Institutes of Health. Retrieved November 27, 2021, from https://orwh.od.nih.gov/sex-gender/nih-policy-sex-biological-variable.
Comments