For patients who suffer from migraine, it’s always important to keep abreast about new information about migraine patterns and epidemiology. Dr. Kuruvilla recently edited an article on gender and migraine with the amazing writer Brooklyn A. Bradley. Please check it out!
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Sex Differences in Migraine
Brooklyn A. Bradley
Migraine is a disabling neurological disease with a variety of symptoms and subtypes. According to the American Migraine Foundation, at least 39 million Americans live with migraine1. Migraine affects everyone in different ways and at various moments in their life. You may experience headaches more frequently at a young age, or maybe as you get older you will experience a different variety of symptoms than you have before. Either way, migraine consists of genetics, environmental factors and triggers which leads to the symptoms commonly seen in people with migraine1.
There have been sex differences found in the brains of people who have migraine2. Research in the area of sex differences reveals information about the role that sex plays in migraine expression. You might be wondering what sex differences have to do with migraine. Well, let’s start with a few definitions. There is a lot of debate on the definitions between “sex” and “gender.” Sex is a biological variable defined primarily by sex chromosomes (tiny structures made of DNA and protein) and sex steroid hormones (chemical messengers in the body). Individuals are distinguished as female or male specifically on the presence of their reproductive organs and structures. In contrast, gender is a psychosocial concept determined mainly by family, society, and culture. Gender is a socially based phenomenon that consists of a range of variables. On one end of the spectrum are exclusively feminine characteristics while the other end is exclusively masculine, with numerous identities that fall between these two2.
Sex differences refer to the differences in mental functions and behaviors of the sexes. It is an emerging field of neuroscience and psychology, and it has numerous applications in medicine3. Hormones regulate most aspects of social behavior, more specifically cognition, interactions, and aggression. Hormones are chemical messengers that travel to different parts of the body where they aid in the regulation of cell and organ function. Some of the most common chemical messengers that we talk about in the field of sex differences in the brain are classified as gonadal hormones, or hormones that emerge from the gonads (testes in male and ovaries in female). In females, these gonadal hormones include follicular-stimulating hormone (FSH), luteinizing hormone (LH), estrogen, and progesterone. In males, testosterone is the gonadal hormone. The levels of gonadal hormones change as we develop and age, which may help us to understand why one sex may experience worse symptoms or disease than the other3. We now know that hormones can affect each sex’s expression of a particular disease or illness — with today’s article focusing on migraine.
Women are two to three times more likely than men to have migraine4. Migraine research has shown a direct relationship with hormonal changes. Estrogen is the primary hormone linked to migraine. So — what is estrogen exactly, and why is it influential in migraine? During a woman’s menstrual cycle, the levels of estrogen are constantly rising and falling. Estrogen changes are most pronounced during menstruation, pregnancy, breastfeeding, perimenopause, and menopause. Estrogen is a hormone that acts on serotonin, a neurotransmitter that regulates pain and mood as well as several other chemical exchanges within the brain4.
In women, migraine often begins at puberty and tends to improve after menopause5. The recurrence of migraine has been seen during the premenstrual and menstrual phases of the reproductive cycle in women 5 which indicates that the decrease in gonadal hormones that occurs during these phases may influence the presentation of migraine in some women5. The premenstrual phase typically emerges a few weeks before the start of bleeding, and is characterized by low estrogen levels. Migraine has been found to occur more prominently during the premenstrual phase, where there are low levels of estrogen. Menstrual migraine is a migraine that begins a few days before menstrual flow and ends about halfway through a woman’s period. During this span of time, estrogen levels drop. Thus, to extend the scope, you can think of steady or increasing levels of estrogen as reducing the risk of migraine5.
There is clearly a complex relationship between estrogen and migraine but it is not completely understood. It is important that sex and gender-related differences are acknowledged in both migraine and headache research. Researchers are still in a race to understand the factors that put women at a greater risk for developing migraine. Once we are able to accomplish this, we can be better equipped when counseling people with migraine about potential treatment options. The topic of sex differences in migraine has so much potential, because it can lead to an innovative gain in the area of women’s health.
References:
- What Is Migraine? In: American Migraine Foundation. https://americanmigrainefoundation.org/resource-library/what-is-migraine/. Accessed 25 Nov 2021
- Peterlin BL, Gupta S, Ward TN, MacGregor A (2011) Sex Matters: Evaluating Sex and Gender in Migraine and Headache Research. Headache 51:839–842. https://doi.org/10.1111/j.1526-4610.2011.01900.x
- Choleris E, Galea LAM, Sohrabji F, Frick KM (2018) Sex differences in the brain: Implications for behavioral and biomedical research. Neurosci Biobehav Rev 85:126–145. https://doi.org/10.1016/j.neubiorev.2017.07.005
- Eisenstein M (2020) Closing the gender gap in migraine research. Nature 586:S16–S17. https://doi.org/10.1038/d41586-020-02867-4
- Somerville B (1972). The role of estradiol withdrawal in the etiology of menstrual migraine. Neurology Apr 1972, 22 (4) 355; DOI: 10.1212/WNL.22.4.355