Migraine and Hormones: New Ideas Needed

This transcript has been edited for clarity. Indira Subramanian, MD: Hi. Welcome, everyone, to Medscape. I’m so excited to have Professor Andrew Charles on today. He is a professor of neurology at UCLA and the director of the Goldberg Migraine Program at UCLA, a good friend and colleague, and he actually was my residency program director back in the day.We’re here debunking migraine mythology. My name is Indu Subramanian. I’m a neurologist at UCLA as well. Welcome, Andy. Thank you for joining us.Andrew C. Charles, MD: Thanks, Indu. Great to be here.The Hysterical Woman StereotypeSubramanian: One of the mythologies around migraine is this stereotype that it’s these hysterical women that have a large amount of emotionality and issues with dealing with their stressful marriages, and [hectic] days, and kids, and everything...and this is who gets migraine because of the stress and the profile.As somebody who myself has migraines and auras, I find this to be an old-school thought process, even across neurology. You know that I’ve been passionate about elevating voices of women living with Parkinson’s, understanding the specific issues around that, and how some of the stereotypes can affect anyone living with disease.I’d love to hear your thoughts, Andy, about this and how we can do better.Charles: I’ll start by blaming our psychiatrist colleagues for the Freudian idea of the hysterical woman, which really is something that has been attached to migraine for quite some time. Just a little background. So in boys and girls, migraine has more or less equal prevalence. At the time of puberty, it spikes in women and becomes three times as common in women as men. Then around the time of menopause, there’s often an exacerbation of migraine, and then it settles down, but still remains two times as common in women as men. Clearly, issues around sex and hormones are involved.There are other important things to point out. Migraine commonly is exacerbated at the time of the menstrual period in many women. It often gets better during pregnancy. It can be worsened or sometimes improved by birth control, so clearly there are many hormonal issues involved. As you mentioned, it really is something that we haven’t done a very good job at all of really getting into the mechanisms for that. Are they hormonal? Are they chromosomal? The view of it has been very simplistically focused on estrogen. To me, that’s one of the biggest areas of misunderstanding or lack of understanding in terms of migraine. What really is going on at the hormonal level, and how do we more effectively go after it in ways that are helpful for women without causing side effects?More Complicated Than Falling EstrogenSubramanian: You’ve been a bench researcher and an amazing clinician for decades. Often, we’ve excluded female mice because of complications, probably not tested many medications in women of childbearing age, and haven’t even really needed to report numbers of women in studies until relatively recently, right? Maybe you could speak to that.Charles: It’s another example where a paradigm got established and people just followed along the paradigm. The paradigm is that falling estrogen levels trigger a migraine attack, especially around the time of the menstrual period, and that if you supplement estrogen during that time, it could be helpful.That’s also used as the explanation for why migraine gets better during pregnancy — that it’s simply that estrogen levels are higher. That is such a simplistic view that more estrogen is good and less is bad. We also know that if you use high-dose estrogen preparations in migraine patients, it will often make things worse, so that doesn’t make sense. It also just doesn’t acknowledge the really intricate feedback mechanisms that are involved in the neuroendocrine axis. What most people don’t think about is that really the master clock of the neuroendocrine axis is the hypothalamus. Most people also don’t know that about every hour in all of us, for our entire life, there’s this pulse of gonadotropin-releasing hormone that happens in both men and women. The frequency and amplitude of that changes with hormonal changes. It’s one of the most robust clocks in the body, and it’s something that people really don’t pay attention to, particularly as it pertains to what the effects are if you take estrogen.If you take one dose of estrogen a day, you can think about it like a big hammer on a very delicate system, and you’re not necessarily sure what effect that is going to have. You can think about just estrogen levels, but what effect is taking exogenous estrogen going to have on this really finely tuned machine?We have to get much, much better at thinking about timing of dosing, whether we should do cyclical dosing or single dosing, whether we should combine estrogen, how much we should combine it with progesterone, and should we actually be targeting further upstream like the hypothalamus or the pituitary, rather than downstream, the estrogen, progesterone, and testosterone, for example.There are many open questions there, but I think it’s an opportunity for us to really make some headway in more specifically treating migraine in women in ways that we really should have been doing all along.Subramanian: Migraines are more common in women by how much?Charles: It’s 3 to 1, so about 25% of women of childbearing age have migraine. It’s pretty extraordinary. One way of thinking about migraine really is a women’s health problem. As you alluded to, I think I’ve always thought that part of the reason that it hasn’t really received much attention is because it predominantly affects women.That’s something that fortunately is now changing. With all the other progress that we’re making with new therapies, I think we’re getting greedier about getting better at treating the whole population and specifically women.Subramanian: Hallelujah! It’s about time. Well, thank you so much, Andy, for joining us, and thank you, everyone out there, for joining us today.Charles: My pleasure.