Additional details on the connection between transgender HRT and migraine headache patterns

Disclaimer: I am not a medical professional and this is not medical advice.

A migraine headache is an astonishingly miserable experience, ever surprising in not only its intensity but its diversity. This is not the milder tension headache or such a common headache but stronger and longer, this is a complex neurological syndrome that can affect us in many disabling or sheerly unpleasant ways. An affliction passed from my maternal grandfather to my mother down to me, since age 3 I’ve had some of the most memorable experiences of my life thanks to frequent migraines. Vomiting so profusely I’d need to be taken home or miss school at least once a week, laying for countless hours in the dark able to do nothing but wait for it to pass, I became intimately familiar with lengthy periods of unbearable, intractable, inescapable pain from a young age.

As I’ve grown, I’ve racked up more and more of the comprehensively bizarre symptoms of migraines: the occasional visual aura of apparent static in the center of my field of vision, the far more subtle feelings of abnormally higher or lower energy or inability to focus in the days preceding it, the near-hallucinatory racing thoughts that I can’t shake as I writhe around the bed fruitlessly trying to get any respite, the euphoria or simple exhaustion that comes when it finally remits. I’ve experienced a range of treatments over time as well, from Motrin that barely touched it, to Excedrin truly making a dent in it for the first time, to triptans that could free you from this in an hour but must come from a pharmacy whose schedule your body has no regard for, to the rebound headaches that make it seem like there can never be such a thing as a free lunch here. I’ve not yet needed some of the other treatments for migraine sufferers, such as facial botox injection, older antidepressants like amitriptyline, anticonvulsants like Topamax, long-acting preventative CGRP inhibitors or short-acting abortive CGRP inhibitors.

One key experience at the nexus of migraine symptoms and medical treatment over time is the way that sex hormones, including masculinizing puberty at a normal age and later feminizing HRT at 23, have shaped and altered these experiences. The wave of testosterone in my early teens acted within less than a year to bring my frequent migraines down to merely a couple times a year. And when I started taking estrogen and antiandrogens, it was a matter of days before I had one of my worst migraines in years, which have since become a once- or twice-monthly occurrence during the eight years I’ve been on HRT.

Migraines are a subjectively awful and torturous experience that can have a devastating impact on one’s overall quality of life. An understanding of how cross-sex hormone therapy may influence migraines can illuminate options for trans people to attain better control and management of these symptoms. The role of sex hormone levels, particularly estrogen, in patterns of migraine headache was first established from observations of large populations of cis people: migraine is far more common in cis women than in cis men; it increases in cis girls with the onset of feminizing puberty (Jamieson, 2017); fluctuations in hormone levels throughout the menstrual cycle are temporally associated with migraine headaches; and hormonal contraceptives can have the effect of increasing or decreasing migraine frequency in cis women (Chai et al., 2014).

Additionally, in trans women, taking estrogen has been associated with a greater likelihood than cis men of experiencing migraine, more in line with the higher prevalence of migraine seen among cis women (Pringsheim & Gooren, 2004). Some trans men have also been observed to have a reduction in migraines after starting testosterone, a treatment which tends to reduce their estrogen levels substantially. MacGregor & Maassen van den Brink (2019) have suggested that the especially high and low estrogen levels experienced by trans women and transfeminine people due to intermittent HRT dosing can play a role in causing migraines, and in causing particular types of migraines. Oral estrogen may be taken 2 or 3 times a day, estrogen injections are typically performed every one week or two weeks. Any of these doses of estrogen creates an initial spike in estrogen levels, wearing off to the lowest trough immediately before the next dose.

The authors note that these very high estrogen levels are associated with migraines with auras, while low estrogen levels at the trough are associated with migraine without an aura. The nature of most HRT dosing may therefore predispose trans women to having migraine headaches triggered, and a variety of types of migraines as well. They suggest that migraines can be reduced by using as low a dose of estradiol as necessary, and preferably via a transdermal formulation such as patches, which last several days and release a more steady and consistent dose of estrogen into the body. Crucially, as noted by the Transgender Headache Medicine Program at Mount Sinai, transgender people do not have to discontinue their HRT while receiving treatment for migraines. And we can generally receive the same treatments as a cis person with migraines.

Recent reviews (Ailani, 2021) have highlighted the role of, not a specific level of hormones, but the occurrence of sharp rises and falls in hormone levels as a trigger for migraine: cis women with menstrually-associated migraines were given a blocker to halt estrogen production and then administered transdermal estrogen, which was more even in its levels than their bodies’ own production of estrogen, resulting in a strong reduction in migraines (Reddy et al., 2021). Unfortunately, little is known about which migraine treatments may perform better or worse under conditions of feminizing or masculinizing HRT, although van Casteren et al. (2021) found that among users of triptan drugs, cis women took more medication than cis men, and cis women were more likely than cis men to have a later recurrence of migraine after using the medication. Both long-acting CGRP inhibitor treatments and short-acting CGRP inhibitor treatments have not down a difference in their effectiveness between those assigned female and those assigned male (Gazerani & Cairns, 2020).

Because migraine, especially migraine with aura, may be associated with a greater risk for thrombosis (blood clots, including those causing strokes, heart attacks, and pulmonary embolism), trans people with migraines should avoid smoking, be attentive to their cardiovascular health, and consider any impact that estrogen or testosterone might have on their personal risk for thrombosis. However, in a recent study of 611 trans adolescents on cross-sex hormones, none experienced any events of thrombosis, and the risk does not appear meaningfully elevated by HRT (Mullins et al., 2020). Transmasculine adolescents who experience gender dysphoria due to menstruation may, even without testosterone, access various hormonal contraceptives to produce suppression of menses (Pradhan & Gomez-Lobo, 2019), and they should be aware of the potential for some of these medications to affect an individual’s experience of migraine headaches.

Migraines suck. They just suck. Nobody wants to deal with this, and nobody should have to. Yet in my lifetime, I’ve witnessed the progression of treatments that can make migraines a much smaller part of our lives, and increasing knowledge of how trans people as a population can best manage migraine headaches during our transitions. Each individual’s experience in dealing with migraines may be different, but none of us is alone in this. ■