Guest: Caroline Stowe, DNP, FNP-BC, AAHIVS, AQH, MSCP

View the recording from our Migraine Clinician Masterclass, developed in partnership with IVPN Neuropsychiatry. In this webinar, we hear from Caroline Stowe, DNP, FNP-BC, AAHIVS, AQH, MSCP, who discusses managing migraine symptoms during menopause and perimenopause. Please note that this video is intended for healthcare providers.

TRANSCRIPT

Caroline Stowe, DNP, FNP-BC, AAHIVS, AQH, MSCP: Good evening or good morning, depending on where you’re joining us from today. My name is Caroline Stowe, and I’m a doctorally prepared family nurse practitioner in the Washington, DC area of the United States. As both a headache and menopause specialist, I carry an additional qualification in headache medicine from the National Headache Foundation, as well as being a menopause society certified provider from the Menopause Society of North America. I have the pleasure today of speaking on the management of migraine symptoms during perimenopause, menopause, and some effective treatment strategies that exist today. 

I have no financial relationships or disclosures to report, and I also want to ensure that you know the information presented today is considered up to date as of today. But information changes so quickly in the headache world and the menopause world that very soon it may be considered out of date. 

So first, I’d like to define what we’re talking about from the start. Migraine isn’t just a terrible headache. It’s a disabling neurological disease with different symptoms and different treatment approaches compared to other headache disorders. All of us who work in neurology and headache medicine know that the migraine brain is a hyperexcitable brain. I also want to state that my use of the word female, woman, women, she, her, hers pertains to all individuals who may not identify as such but biologically can experience perimenopause and menopause.

Now, perimenopause is the time in a woman’s life when menstrual periods become irregular as she approaches menopause. This is usually about three to five years before menopause and is often marked by many of the symptoms of menopause including hot flashes, mood swings, night sweats, vaginal dryness, trouble concentrating, and infertility. And then last, looking at menopause, it’s the final menstrual period and is usually confirmed when a woman has missed her period for 12 consecutive months with no other obvious causes.

So why do we care about migraine? Well, it affects over 1 billion people worldwide. It has a very high prevalence and morbidity especially among young adults and women. In 2016, globally, it was the second largest contributor to the disability-adjusted life years lost due to neurological disorders. It is the highest cause of disability among women ages 15 to 49. This is a huge time for women, right? 15 to 49 they are their most productive years. 

They’re starting and finishing their education journey. They’re potentially getting married and having children. They’re starting careers. Their careers are flourishing. And they’re caring for family – whether young or older – all of this is happening during this time period. We know that it disproportionately affects women with the overall prevalence being about 20.7% in females and 9.7% in males. And this number right here, 42% of all women will have had an episode of migraine in their lifetime. That’s almost half of all women. It’s huge. 

Now, the woman’s reproductive cycle is regulated by the hypothalamic-hypophyseal ovarian axis through the release of estrogen and progesterone. Variations in the levels of these hormones and of their feedback control regulate the menstrual cycle, pregnancy, and menopause, among other things. Estrogen is the key hormone responsible for this fluctuation. Estrogen has facilitatory and inhibitory effects on various neurotransmitter systems, including the serotonergic, glutaminergic, opioidergic, and GABAergic systems.

Estrogen receptors occur in the trigeminal ganglion, and animal studies have shown that estrogen modulates calcitonin gene-related peptide, CGRP, expression and the different components of the trigeminovascular system. The role of progesterone is a little less clear. It mainly activates GABAergic systems and can modulate the actions of estrogen in the central nervous system.

Now, we know that sexes are equally affected before puberty, highlighting the importance of hormonal influences. But once girls reach puberty, we generally see more migraines. Throughout the reproductive years, menstruation is one of the most significant events related to the occurrence of migraine attacks. Compared with all other phases of the menstrual cycle, the incidence of migraine without aura is greatest during a five-day window that starts two days before the onset of menstruation and continues through the first three days.

Now, most epidemiological studies have demonstrated that the majority of women suffering from migraine note remarkable and increasing improvement of their attacks during pregnancy from the first to the third trimester. Improvement is more likely in women with a history of menstrual migraine. If migraine does not improve by the end of the first trimester, it’s likely to continue throughout their pregnancy.

In fact, a small number of pregnant women will experience a worsening of their migraine while a few others may even develop de novo migraine symptoms. The worsening usually occurs during the first trimester and involves women suffering from migraine with aura rather than migraines without. Recent data show that approximately one-third of all perimenopausal cycles have a major surge in estradiol occurring de novo during the luteal phase.

This phenomenon called luteal out of phase or loop event may explain a large proportion of symptoms and signs for symptomatic perimenopausal women. A wave of follicle growth that is initiated in the prior luteal phase causes very early ovulation immediately after or concurrent with menses from the prior cycle. Higher estradiol levels and rapid reexposure to progesterone result.

Now during the transition to menopause, some women may experience a worsening of the migraine attacks, but usually postmenopause is also associated with relief. The type of menopause has a substantial effect on migraine. Natural menopause is associated with a lower prevalence of migraine compared to surgical menopause.

The longer the time interval is from menopause onset, the greatest is the association with improvement. Whether migraine is associated with other menopause symptoms is still unclear since there’s conflicting data and more studies are being done. In contrast to the effects of menopause on migraine without aura, prevalence of migraine with aura does not generally improve with menopause.

Now estrogens are a group of hormones that play an important role in the normal sexual and reproductive development in women. I love this picture because it pretty much affects everything, right? These are also known as sex hormones, and the woman’s ovaries make most estrogen, although the adrenal glands and fat cells also make small amounts. In addition to regulating the menstrual cycle, estrogen affects the reproductive tract, the urinary tract, the heart and blood vessels, bones, breast, skin, hair, mucous membranes, pelvic muscles, and the brain.

Secondary sexual characteristics such as pubic and armpit hair also start to grow when estrogen levels rise. And many organ systems, including the musculoskeletal and cardiovascular systems and the brain, are also affected. Now I also want to call out that estrogen helps preserve bone density, and we know that osteoporosis is such an important issue in our postmenopausal women. Now to learn more about women’s health and specifically hormone replacement therapy, the National Heart, Lung, and Blood Institute of the National Institutes of Health – also known as the NIH here, in the US – started a large study in 1991.

It was called the Women’s Health Initiative. And the hormone trial had two studies. We had the estrogen plus progestin study of women with a uterus and the estrogen alone study of women without a uterus. Both studies were concluded early when the research showed that hormone replacement did not help prevent heart disease, and there were some increased risks for some other medical problems. So the FDA here, in the US, states that hormone therapy should not be taken to prevent heart disease. 

Now, I like this graph because it shows just how impactful hormones are on individual triggers occurring at least occasionally. Hormones is number two. Stress is number one.

Somehow I doubt that surprises anyone here. I also think it’s important to point out that so much of what triggers migraine can feel uncontrollable, but there are several things we can help encourage our patients to do to help regulate that hyperexcitable brain. 

We know a migraine brain likes things to stay the same. So for example, you can see here sleeping late can be an individual trigger. So, if they’re only getting migraines on the weekends, talk to them about the fact that maybe it’s sleeping later that does it to them and have them set their alarm to get up at the same time every day. That might just fix it.

Now menstrually related migraines defined as attacks that occur in the perimenstrual period but can occur at other times of the cycle as well. While pure menstrual migraine is diagnosed when attacks are purely confined to the perimenstrual period. This is important to understand as the treatment options can vary between the two. If someone has pure menstrual migraines, the shorter-acting triptans, like sumatriptan, don’t generally work. The longer-acting ones like Frova and naratriptan will be better suited to provide relief. 

And for example, we use Frovatriptan. It’s a 2.5 mg tablet by mouth either daily or twice daily for six days, starting two days prior to onset of their anticipated menstrual migraine. And naratriptan is the 1 mg by mouth twice daily for five days, again, starting the two days prior. Now the trick here is that these menstrual periods need to be predictable, right? And we know that’s not always the case with our patients, and a typical menstrual cycle can shift, and many women don’t have regular cycles. But this can be sort of a little tool in your toolkit of things to use for these menstrual migraines.

Now the goal for treatment in those with menstrual migraines is to reduce that drop in hormone and to stop ovulation. One of the ways that we can do this is with the use of hormones like progestin only and/or combination type contraception, meaning estrogen plus progestin. The progestin only method is generally a good fit for those who can’t tolerate estrogen, whether it’s due to side effects or they have migraines with aura.

In the US, we have several different options. And the majority of these will actually cause a patient’s period to stop by around the six-month mark. But prior to that, it can cause irregular bleeding, which can be really frustrating, and you’re going to hear from your patient about it. Combination options have more predictable bleeding so it can feel more regulated than a progestin only method within the first three months. You can also skip your period on purpose with this option by avoiding the placebo pills in days and jumping to the next pack, ring, patch, what have you.

By doing this, you’re avoiding that estrogen drop. Some patients will need to allow for an active pill break due to breakthrough bleeding. Some don’t have to worry about it at all, and they can just keep skipping and skipping.

Nonsteroidals can be used in conjunction with triptans or alone in a similar way as we use the Frova and the naratriptan two days prior to onset of their menses. The nice part to this is that we use NSAIDs in patients with dysmenorrhea, right, so two birds, one stone. And while we here, in the US, encourage the use of magnesium, if somebody doesn’t want to use that every single night, they can use it just for their pure menstrual migraine just prior to onset of menses and during their cycle and then stop them.

So talking about magnesium, the most substantial evidence for its effectiveness is in patients who have or have had aura with their migraine. It’s believed magnesium may prevent the wave of brain signaling called cortical spreading depression, which produces the visual and sensory changes and the common forms of aura. 

Other mechanisms of magnesium action include improved platelet function and decreased release or blocking of pain transmitting chemicals in the brain such as substance P and glutamate. Magnesium may also prevent the narrowing of brain blood vessels caused by the neurotransmitter serotonin. Taking magnesium 15 days after the start of your period and then continuing to take it until the start of the next period can help manage those menstrual migraines. 

Now perimenopause is really where we see in this graph the hormone levels all over the place. This time can be very challenging for women beyond just their medications not working for their migraines as they once were or worsening migraine symptoms. They’re beginning to experience the menopausal symptoms of brain fog, vaginal dryness, mood changes, etc. By our late thirties, we don’t produce as much progesterone and the number and quality of follicles also diminishes causing a decline in estrogen production and fewer ovulations.

As a result, by our forties, cycle length and menstrual flow may vary and periods may become irregular. Estrogen may drop precipitously or spike higher than normal. And over time that FSH level rises in vein and the vein attempt to prod the ovaries into producing more estrogen. Although a high FSH can be a sign that perimenopause has begun, a single FSH reading is not a reliable indicator because day-to-day hormone levels can fluctuate dramatically.

Now let’s talk about treatment of migraines during the perimenopausal time. It’s important to keep in mind what else is happening with your patient. We need to consider all other comorbid conditions like hypertension, mood disorders, depression, anxiety, sleep disturbance. They coexist and it will be difficult to treat one without also treating the other. So if your patient has hot flashes, tell them to avoid warm rooms, hot drinks, hot foods, alcohol, caffeine, excess stress, and cigarette smoking. Consider ways to reduce stress and promote more rest with tai chi, yoga, meditation, biofeedback.

Although many nonprescription remedies reduce hot flashes, it’s likely that this is because of the placebo effect. When non-prescription treatments are studied scientifically, they typically are as effective as a placebo. Even if relief is because of the placebo effect though, you can expect your hot flashes or your patient’s hot flashes to decrease by about 30% with most non-prescription remedies such as soy, herbs, or acupuncture.

Prescription hormone therapy with estrogen is the most effective treatment for hot flashes. Although using hormones can increase the risk of breast cancer and cardiovascular disease, studies show that benefits may outweigh the risk for healthy women younger than age 60 with moderate to severe hot flashes. The goal is to use the lowest dose of hormone therapy that treats their symptoms for the shortest time necessary.

Women with a uterus need to combine estrogen with a progestogen. With migraineurs, we recommend a daily versus a cyclical progestogen, and it’s generally recommended to use the transdermal types such as estrogen patches, gels, or sprays as these maintain stable hormone levels with few fluctuations. There are other options for women with a uterus that combine estrogen with, you know, something like bazedoxifene to protect the uterus.

It’s an estrogen agonist/antagonist, which means it works like estrogen in some tissues and then opposes estrogen’s actions in others. If it’s not been a full year since your patient’s last period and they’re a healthy nonsmoker, you can consider a combination estrogen/progestin birth control pill. So we’re getting contraception, we’re getting hot flash relief, and we’re regulating our periods. Of note, it’s not indicated to use hormone replacement therapy purely for migraines. And I also want to make it clear that it’s not contraindicated to use estrogen as hormone replacement therapy in people with migraines with aura because it’s such a low dose. 

Now, those who experience high blood pressure can benefit from antihypertensives for both blood pressure control and for migraine prevention. Here, in the US, we love our candesartan, we love our beta-blockers, for example, but there are other options as well. And looking at migraines with mood changes, you know, we have venlafaxine and escitalopram are two of our favorites. We know venlafaxine has been well studied and can really help with vasomotor symptoms. I will tell you escitalopram is one of my favorites for migraine prevention.

It’s very fast acting. You’re going to know how they’re doing in about two weeks. You’ll get a lot of people that say we don’t use that for migraine. But it really works well. And remember, if you’re not treating the mood disorder, you’re not going to be treating their migraines effectively. 

Now in patients who experience migraine with sleep disturbance, amitriptyline or nortriptyline are our ideal choices. As most of us are aware, menopause can bring difficulty in maintaining one’s typically well-managed weight, and topiramate is one of the only preventatives that has weight loss as a potential side effect.

Now a new study, in 2023, found for female participants with migraine, their levels of the protein CGRP, calcitonin gene-related peptide, that plays a key role in starting the migraine process also fluctuate. This elevated level of CGRP following hormonal fluctuations could help to explain why migraine attacks are more likely during menstruation and why migraine attacks gradually decline after menopause. Now of course, these results need to be confirmed with larger studies, but we’re hopeful that they will help us better understand the migraine process.

And I bring this up because we love using our CGRP inhibitors, our mAbs, and our gepants as preventative options. And so this study was a really good indicator that what we’re doing is to keep doing it. We love our Botox for chronic migraines. And we’ll talk more about neuromodulators in the next slide, but we love using those as well for prevention. 

Now, I don’t know how familiar you are with neuromodulators, but they’re noninvasive options. They don’t have to be implanted, they’re portable, and patients use them in various ways, and they don’t have significant side effects. The FDA calls them nonsignificant risk devices. And they change the way the brain processes pain by various mechanisms from various approaches. Now, one of the advantages of these is that besides the fact that they don’t have side effects is that when medications have failed, it’s often because, you know, we kind of chose the wrong option.

We thought we were targeting something and we really needed to target something else. And that’s how medicine works, right? It targets a particular chemical within the brain. And the advantage of going into the brain and slowly changing the nerves is that you’re affecting those targets that we know about but also targets that we don’t know about. And so many patients who have had a lack of success with medicines, the medicines have failed one after another, will find that neuromodulators can really help. And it kind of gives them hope again, right? But you need to consider cost here, you need to consider insurance coverage, especially in the US, and how frequently your patient may need or want to use it when deciding which of the neuromodulators might be a good fit.

Looking at our abortive treatments, we have our triptans, right? These are our OG of abortive treatment for migraine. They can still be used very successfully during the menopause period, just watch for cardiovascular disease. Certain arrhythmias with Parkinson-White, they’re contraindicated for use. We love our gepants here. They have fewer side effects, fewer drug interactions, they do have a bit of a slower onset but a longer half-life. And we like combining them all together, honestly.

Please don’t ever forget to offer your patients an antiemetic. Even if they don’t talk or, you know, discuss having nausea, it can help a lot with pain. And I always offer it to my patients as if you do experience nausea, and I’m not right there with you to prescribe something, I’d rather you have it on hand. And then, of course, the neuromodulators. So you heard we can use neuromodulators for both prevention and for acute or abortive use as well. 

Now we’ve reviewed magnesium, and it’s really one of the most well-studied supplements in migraine prevention. We also have riboflavin, also known as B2, and it’s a vitamin that’s found in foods such as organ meats, fortified breakfast cereals, oats, dairy, and more. It’s unclear how this B vitamin helps with migraine, but it may be because riboflavin helps with energy metabolism of the cells and decreases certain neuroinflammatory substances. 

People living with migraine have been found to have lower levels of riboflavin compared to those without migraine. And a study that I referenced here later, at the end of this presentation, found that supplementing with 400 mg of riboflavin decreased the number of headache days compared to placebo, but as usual, more studies are needed. 

Now there’s CoQ10. It’s a compound that’s present in almost every cell in the body and is largely responsible for energy production. CoQ10 may help those with migraine by decreasing inflammation, improving cell energy, and reducing CGRP. A study found that CoQ10 levels are lower in those with migraine than in those without. And a recent review of six studies found that CoQ10 was effective in reducing the duration and frequency of migraine attacks.

And last, we have omega-3. It’s a fatty acid that you have to get from your diet, right, your body does not make this naturally. Omega-3s are thought to be beneficial for migraine, because they regulate serotonin levels in the brain, they reduce inflammation, they decrease the number of inflammatory proteins. Common sources of omega-3s include fatty fish, flax seed, chia seeds, walnuts, and soybeans. And a study found that diets high in omega-3s were able to reduce the frequency and intensity of migraine attacks. 

And this study also found greater results when the diet had high levels of omega-3s and low levels of omega-6s. Now there are other supplements that you will hear about from different types of providers and different healthcare providers, but I will always tell my patients to take these. Go ahead and get started on these because there are very few drug interactions and risks. There are other ones, there are a few, that I don’t always recommend depending on the patient’s health status, so these are my four favorites. 

Now, thinking about menopause, we know that 75% or three-quarters of women who experience migraine will have complete cessation of their migraines after menopause. So this is great news, but that still leaves a quarter of our patients who will experience migraines still or potentially have worsening of their existing migraines. The same treatments apply and the same considerations that we reviewed apply.

Now something that I get a lot of questions about dealing with surgical menopause when a woman has had a hysterectomy with ovarian preservation, we know those hormones will still fluctuate for a little bit and they’ll take some time to stabilize. So it’s not a light switch that kind of cuts on and off like when we have the ovarian removal. So you have a sudden drop in estrogen, and up to 70% of women will experience worsening migraines. So, if you know your patient’s going to have this type of surgery, be prepared and be ready to hop on to make sure that we’re really optimizing their migraine care. 

Now this study just came out. I just added this slide yesterday. A new study was published this month reporting that women in menopause who have both migraines and vasomotor symptoms have a higher risk for heart disease or stroke. The study averaged data from nearly 2,000 women ages 18 to 30 enrolled in the NHLBI-funded Coronary Artery Risk Development in Young Adults, also known as the CARDIA study. The research team followed the women for 15 years and recorded cardiovascular disease events and strokes combined with data on frequency of migraines and vasomotor symptoms during the study period. It was as if they knew I was giving this presentation and they needed it published. 

The researchers discovered that the risk of developing heart disease was one-and-a-half times greater among women who regularly had both early adulthood migraines and persistent and frequent vasomotor symptoms during menopause compared to women who very rarely or never had these symptoms. Additionally, the women with combined migraines and vasomotor symptoms had a 1.7-time greater risk of having a stroke, yet having a history of migraine or vasomotor symptoms alone did not increase the risk of heart disease or stroke.

The researchers also found that the risk levels for both heart disease and stroke declined after the team adjusted for traditional cardiovascular risk factors such as cigarette use, cholesterol, blood pressure, those kinds of things. So what does this mean for our patients, right? We need to listen very carefully. We need to ask the appropriate questions to help parse out if your patient is experiencing signs and symptoms that need to be followed up on or monitored more closely. And as usual, we need to encourage them to live healthy lifestyles – quit the smoking, moderate alcohol, increase exercise. Let’s really make sure we’re eating well. It makes a big difference.

So what are hormone replacement therapy effects on migraine? Well, the general consensus is that 75% of patients will have no change in their migraines when they start HRT, or they’ll have improvement. And then 25% will have worsening symptoms. So keep in mind that we generally ask our patients to give treatments at least six weeks’ worth of an effort unless they’re having significant side effects. And tell them reach out with any questions, right? Don’t just hang on and think, oh, well I can put up with it.

We want to know right away. We like to see effects after three to six months for other medications, right, we think CGRP, hormone replacement is another one, of course. So you likely are not going to see immediate changes, so this is where the importance of tracking your headaches comes in.

Now I pulled this from the Association of Migraine Disorders. I really like this headache tracker. It helps the patient and it helps you. So the longer your patients track their migraine, the more both of you will get out of the tracker, right? It’s considered one of the most important tools in both the patient and headache specialist toolkit. Over time, patterns will begin to appear, helping us to understand patient’s triggers, how the medications are affecting the patient and more. 

Now one of the major benefits of tracking is that your patient can literally bring this into you.

They can email it to you. It helps to improve your treatment strategy. It also helps to decide, you know, if hormone replacement therapy is improving or worsening migraines. I will tell you that I make treatment decisions based off of headache trackers all the time. Patient will tell me I had a headache for X amount of days. And when I look, I can see on the tracker, it was really just one long headache, right? So optimizing their abortive there may be a better choice than changing their preventative.

It’s so much easier to look at a document like this than it is to rely on memory and to recognize the patterns. So how should you track your migraines? Well there isn’t a best answer. Many people find smartphone apps to be the most accessible, but spreadsheets and journals can be just as useful. Whatever works for your patient works for me. 

So in conclusion, just a little bit of a summary. What I want to remind you is that don’t change someone’s medication if it’s working for them. If it’s broken, you’ll fix it, right? If it’s not broken, don’t fix it. So I want you to just remember that menopause is not the end of the world.

Some studies just came out in The Lancet yesterday that it’s not some dark hole, right? Many women do really well, and many people are really excited, honestly, to go through menopause. What I like to tell my patients is that there is light at the end of the tunnel. If you find that the medicines that are not typically working for you, you’re struggling, you’re really feeling like you’re just having headaches more and more, we’re going to get you through it. But the majority of women will have complete cessation of their migraines after menopause.

So there’s hope, right? So we just got to get you through it. Consider adding on hormone replacement therapy. If you are not comfortable prescribing it, you know, reach out to a consultant, reach out to somebody who is, and help your patient. Because if they’re experiencing hot flashes and night sweats and they can’t sleep because they have insomnia, their migraines are not going to get better. We have to really treat the whole person. 

And consider those medications that have the multiple benefits. You know, we really do love polypharmacy in headache medicine. But if you can use one medication – venlafaxine for mood, for vasomotor symptoms, for migraine, for all the things – then choose that one rather than adding on three different medications. I’m a big proponent of exercise, yoga, tai chi, whatever they have in their community that works for them.

I work for a primary care organization that provides tai chi to their patients every week. So it’s whatever that your patient’s willing to do, get them moving. It will help cognitively. It will help so much. And partner with your patient. I always tell my patients, you know, this is plan A. How does this sound to you? And we have plan B, we have plan C, we have plan D. Don’t give up, right? I don’t have a magic wand. I can’t necessarily do it that way. 

But if you stick with me and you build that foundation of trust with your patient, they will do whatever you ask of them. I truly find that if they trust you, they’re on board. Because, you know, I have a lot of patients that say I don’t want to be on antidepressant, Caroline. I’m not depressed. I don’t want to be on something that will change who I am. And when we go through the mechanisms of action, and when we go through the why behind the medication choices and the options that we’re going through, they’re much more likely and much more willing to participate. So, those are just some little tidbits at the end.

I wanted to include the references. A lot of things that I reference are in here today. And so more to come. Again, hop on The Lancet, you’ll see all the new menopause information.

I just wanted to say thank you to the IVPN Network and the Association for Migraine Disorders for asking me to speak today. Truly a pleasure. I’ve loved getting to spend the time with you.

*The contents of this video are intended for general informational purposes only and does not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. AMD and the speaker do not recommend or endorse any specific course of treatment, products, procedures, opinions, or other information that may be mentioned. Reliance on any information provided by this content is solely at your own risk.