S2 E1: Hormones and Migraine

A National Migraine Centre Heads Up Podcast transcript

Hormones and Migraine

Series 2, episode 1

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[00:00:06] Welcome to the Head’s Up podcast brought to you by the National Migraine Centre, the only UK charity treating migraine and headache.


Dr Katy Munro [00:00:15] Hi everybody and welcome back to Series two of our Heads Up podcast. This first one of the series is a special extended edition. I’m Dr. Katy Munro and I’m with Dr. Jessica Briscoe.


Dr Jessica Briscoe [00:00:27] Hello.


Dr Katy Munro [00:00:27] And we are very delighted to have Dr. Anne MacGregor with us who’s a specialist in hormones and migraine, and has been in working this field for many years. So thank you very much, Anne, for coming and joining us.


Dr Anne MacGregor [00:00:38] Thank you for inviting me.


Dr Katy Munro [00:00:39] So, first of all, we know that we see an awful lot of women with migraine, but men get it too, but predominantly about three times as many women as men get it. Is there an easy answer to why that is?


Dr Anne MacGregor [00:00:52] It’s to do with the fact that women have oestrogen hormones that men don’t have, to the same extent and these hormones change. So that’s the reason why more women get migraine than men.


Dr Katy Munro [00:01:05] And the changing hormones can occur, of course, throughout anybody’s life. And the key times I know, puberty, pregnancy and menopause and of course, menstrual cycles. So is there anything that you would specifically say about puberty related changes?


Dr Anne MacGregor [00:01:23] Well, we certainly see that as girls approach puberty, before then the prevalence has been very much the same in boys and girls. And then as girls start to go through puberty, we start seeing a rate of change of increase in prevalence in girls, that doesn’t occur at the same rate in the boys. And many girls will actually start linking the beginning of their migraines to their first menstrual period.


Dr Katy Munro [00:01:51] I saw a patient yesterday who was a 13 year old and she’d had migraines over a number of years, but they got much worse. And when I asked her about starting her period, she said, ‘Oh yes, it was September since then they’ve got worse’. So it was very topical for this podcast.


Dr Anne MacGregor [00:02:06] And of course the ovaries are gearing themselves up even before their first menstrual period. So you start seeing a few changes developing even, you know, maybe six months to a year before that first period kicks in.


Dr Katy Munro [00:02:19] Yes. Around puberty, do you get menstrually related migraine or does that strong link that we see later in life take a while to develop?


Dr Anne MacGregor [00:02:29] The link with menstruation seems to come on a little bit later in life, but certainly around puberty in the girls you might see a flurry of migraine aura which then disappears. They don’t really get it again, but when you ask them, they’ll say, ‘Oh yes, I remember standing on the beach and the sun was really bright and the sea was shining and then suddenly I started seeing these zigzaggy lines moving across my vision but I haven’t had one like that since.’ And what will typically happen is then they’ll get episodic attacks of migraine without the aura. Maybe when they start, if they start combined hormonal contraception, they’re taking it the old way of taking it, 21/7, they’ll then get migraine linked to their withdrawal bleed. Then it’ll sort of settle down often improve during pregnancy. And then by the time they hit their thirties, going into their forties, then that’s when you start typically seeing the link with menstruation and often linked with menstrual disorders as well.


Dr Jessica Briscoe [00:03:25] I think because you’ve mentioned a little bit about contraception, I think a lot of people get a little bit confused about what contraception can be used in migraine with the different types of migraines. It would be quite good to talk about different types of contraception, how it can be used to manage menstrual migraine or menstrually associated migraine and which ones people can use.


Dr Anne MacGregor [00:03:44] I think the first thing to say is that we would tend not to use contraception specifically for management of migraine, but in women who need contraception it can benefit or worsen their migraine if you give the wrong type of contraception. So the first thing to say, in women who haven’t got aura or have never had aura, they can have any method of contraception that they want. And in many cases, most of those methods can be used to manage any menstrual disorders that they have as well. And I have a big bugbear about people talking about risks of contraception all the time and not actually mentioning the fact, for example, that combined hormonal contraception could have been marketed as a protective drug against ovarian cancer because it naturally halves the risk. And the benefits tend to outweigh the risks for many women, even with migraine. The downside can be when you get women who quite often get migraine with bleeding, for example, you know, if they’re getting it with their period before they start contraception or if they suddenly find that the method that they’re using gives them headaches when they get unscheduled bleeding. So for women who have migraine, we usually find that the methods that result in no bleeding, amenorrhoea, are the preferred method and the most acceptable method to women who have migraine. So that’s things like taking the combined pill without a break at all because there is no scientific reason to any break for the combined pill. But the progestogen-only methods, like the desogestrel pill, can be great for migraine for women who then don’t get a lot of unscheduled bleeding.


Dr Jessica Briscoe [00:05:34] Yeah, I think we had a question about that. So sometimes I think historically people have said, you can double up on the desogestrel pill if you do get bleeding with it. Is there any sort of validity in doing that for people who get migraine if they start having migraines with their bleeding?


Dr Anne MacGregor [00:05:52] Yes. I mean, obviously, it’s unlicenced use of doing so. There are no clinical trials that actually confirm that to be effective. But from a practical perspective, if the woman is tolerating that pill quite well anyway, there is certainly no harm in doubling it up because essentially all you’re doing then is you’re giving the woman the same levels of progestogen, desogestrel, that’s in the combined pill but without the oestrogen.


Dr Jessica Briscoe [00:06:20] Okay.


Dr Katy Munro [00:06:22] So, it’s perfectly safe to do that. And you can do that, sort of, long term as well?


Dr Anne MacGregor [00:06:28] You can do that until a woman reaches the age of 55.


Dr Katy Munro [00:06:31] Okay. Because I definitely did have a question about that the other day and I was just wondering whether the breakthrough bleeding is a sign that the desogestrel hasn’t got control of the ovarian cycle adequately and whether that higher dose would actually reduce that change of oestrogen that little bit better?


Dr Anne MacGregor [00:06:48] I think this is where people get in a muddle about what the different methods of contraception actually do and how they act. So things like the implant and things like the progestogen-only pill or the desogestrel progestogen-only pill, they prevent the release of an egg every month, but they don’t inhibit ovarian activity. So that is why we don’t worry in women who are taking the desogestrel pill about potential low levels of oestrogen and bone protection in later life. But the consequence of having this early follicular phase or early phase oestrogen levels floating around is that they fluctuate. And then that can cause bleeding and it can also cause headaches in women who are susceptible to them as well.


Dr Katy Munro [00:07:34] So it’s quite variable from individual to individual as to how effective that pill is on reducing damping down migraine.


Dr Anne MacGregor [00:07:41] Absolutely.


Dr Katy Munro [00:07:42] It’s just a try it and see if it suits you.


Dr Anne MacGregor [00:07:44] Yes. Women metabolise different hormones in different ways.


Dr Katy Munro [00:07:46] You hear this all the time in migraine.


Dr Anne MacGregor [00:07:49] There isn’t one pill that suits everybody.


Dr Jessica Briscoe [00:07:51] No one size fits all.


Dr Anne MacGregor [00:07:53] And women often think, you know, there is one type of combined pill. And actually we have so many different types of pill that have different doses of oestrogen, it’s different types of oestrogen, it’s different types of progesterone as different doses of progesterone. And essentially you need to try and work out which is going to be the most likely suitable one for that particular person.


Dr Jessica Briscoe [00:08:15] How about the progesterone injections so the Depo-Provera? I saw someone the other day whose doctor was very worried about them being on it. Actually it had managed their menstrually associated migraine quite well and they were saying that their doctor really wanted to take them off. They were in their early thirties actually. And it was more about bone protection, that seemed to be the worry.


Dr Anne MacGregor [00:08:35] Yes. This has been ongoing for beyond the 30 years that I’ve been involved in contraception, that everybody gets really worried about what might happen with bone when you switch it off. But they forget logical things that happen in women’s reproductive life anyway. So when women are breastfeeding, they are essentially putting themselves in exactly the same position in their bone state as when a woman is using Depo-Provera. And as soon as you stop the Depo-Provera, provided a woman is still during her reproductive years, the bone density just goes back to normal. So it’s a temporary shut down of bone density. So the only time you might be concerned about long term use of Depo-Provera is if you’re giving it to a young person and you’re continuing it through the time that they get to their peak bone age. So that they’re missing out that development of the bone. Or if you’re giving it for a prolonged period of time, right at the end of their reproductive life. So you’re in a sense, reducing the amount of oestrogen that they have before they’d have got to their natural menopause. So therefore, that can be a problem.


Dr Katy Munro [00:09:45] So when you say young person…


Dr Anne MacGregor [00:09:46] Yeah. So, you know, if you’re using it in women in their twenties or thirties.


Dr Katy Munro [00:09:54] Right.


Dr Anne MacGregor [00:09:55] And they are then often going to be only using it for a short period of time before maybe they have kids or they want to get pregnant. And then things will change, they’ll shift to a different method afterwards. Worse comes to worse, we can off licence give them natural body identical oestrogen back to give them bone protection. On a clinical perspective, again, no clinical trial data to support that but sometimes you just have to follow logic when clinical trials cannot be done.


Dr Katy Munro [00:10:26] So going back to what you were saying, Anne, about if you have migraine without aura you can use any kind of contraception at all and using it back to back without having a break. I’ve had some patients who say, ‘but I need to have a period to clear everything out’. You know, there is this concept and I know that that’s quite old fashioned. Could you say a bit more about that?


Dr Anne MacGregor [00:10:46] Yes, I think women often feel that it’s important to have their periods to, as you say or as they say, to ‘clear everything out’. But that is when they’re having their natural hormone cycle and as a consequence of that, the lining of the womb is building up each month and it is shed as a period. So there is this misconception that women who are taking the pill 21 days on, seven days off, are having a period every month. But the lining of the womb is being kept really, really thin as a consequence of taking the two hormones every single day. And all that happens during the week that they don’t take the pill is just the empty lining of the womb bleeds as a consequence of the drop in hormones. So they’re not really shedding anything. They’re just bleeding from the open blood vessels that are there in the womb from the hormones being stopped. So nothing is building up. The other thing that people perhaps aren’t aware of is women have many more periods than we were probably designed to do.


Dr Katy Munro [00:11:51] Yes. Of course.


Dr Anne MacGregor [00:11:52] So if you just go to, you know, countries like West Africa or, you know, any of the third world countries, a woman would have started her periods much later because she’s not so healthy and she’ll have spent a lot of her time being pregnant or breastfeeding.


Dr Katy Munro [00:12:09] Yeah.


Dr Anne MacGregor [00:12:09] And so on average, a woman would have about 150 periods through her lifetime. Currently, women have about 450 in modern society.


Dr Katy Munro [00:12:22] Gosh.


Dr Anne MacGregor [00:12:22] And that carries some other potential health risks, too, because every time the body gears itself up to ovulate, then cells are multiplying in the ovaries and every time cells multiply in the ovaries, you are potentially increasing the risk of ovarian cancer. And so that is one of the reasons why ovarian cancer is more common in modern society than it used to be historically. Now, that is not to say women are going to get ovarian cancer. I’m talking about very, very small risks. But it’s just to say that things that people necessarily think are more healthy and may not necessarily be so true. And certainly if women are using combined hormonal contraception, nothing is building up inside them. And we know from ultrasound studies that have been done, where women have taken the combined pill day in, day out for at least a year, that that lining of the womb stays really nice and thin. So keeping healthy.


Dr Katy Munro [00:13:21] That’s really helpful. And I think people will be very interested to hear that. And, of course, the other thing that doesn’t make a build up of the lining is the mirena coil. I think Jessica had a question about that.


Dr Jessica Briscoe [00:13:34] Yes. I mean, sometimes people have said to me, ‘oh, my doctor suggested that I had the mirena coil because it might actually help manage my migraines’. Is that something that can be helpful or..?


Dr Anne MacGregor [00:13:48] The answer to that is yes and no. The Mirena Coil can help one of the potential mechanisms of menstrual migraines. So maybe this is a time to go into the possible methods. So we’re aware of two main, completely independent potential triggers for menstrual migraine. So one of them is that over the course of a normal menstrual cycle, a hormone called prostaglandin builds up within the lining of the womb. And during menstruation, when a woman is bleeding, she releases prostaglandin. The levels of prostaglandin are much higher in women who have menstrual disorders. So, for example, if they’re having heavy or painful periods, they will have higher levels of prostaglandin released. Now, if you give an injection of prostaglandin to anybody will get headaches with nausea and vomiting. And by the by, people found that for the management of their menstrual disorders when they were taking prostaglandin inhibitors. So nonsteroidal anti-inflammatory drugs or more specific ones used for menstrual disorders like mefenamic acid, women would then find, well, actually my bleeding got better, but so did my migraine. That wasn’t so bad. Or studies that have been done using another nonsteroidal, naproxen, where it’s been given pre-menstrually and during menstruation, again has been shown to prevent the development of menstrual migraine as well as reducing menstrual disorders. So the Mirena is very effective at reducing bleeding and therefore reducing prostaglandin. So in a woman who has a menstrual disorder, then the Mirena can be very useful at treating that and the associated migraine.


Dr Jessica Briscoe [00:15:28] Co-treating.


Dr Anne MacGregor [00:15:29] Co-treating the two and that’s often what we’re doing in management of hormonal migraine. We’re always looking at what else is going on in that woman. Does she need contraception? Has she got menopause symptoms? What are her plans for pregnancy? We’re never just treating the migraine alone. But what that Mirena won’t treat is the other potential mechanism that can occur. And that is the natural drop in oestrogen that is known to occur around the end of the menstrual cycle in women. And that’s exactly the same trigger that occurs in women who are taking the pill and having a break. And with respect to the natural drop in oestrogen that still occurs in a woman when she has the Mirena because her natural hormone cycle is still continuing. So the only way you can manage the natural drop in oestrogen most effectively is by shutting down the ovaries, putting them to sleep, and then putting back the oestrogen in a nice, stable way. So that’s the simplest way of doing that.


Dr Katy Munro [00:16:35] Just to clarify what you were saying about using non-steroidals before the period and during. So for example, would it work to take ibuprofen two days before regularly or does it have to be naproxen or is it trial and error again?


Dr Anne MacGregor [00:16:50] Well, I think the studies have been done with naproxen and with mefenamic acid. In my experience, anything that then requires a woman to start timing her periods and calculating, they get very fed up with trying to do that after, you know, not very long. And the thing about this is where is it going to end? So how long do you have to continue doing these strategies for? So that’s why I think although clinical trials can show some of these strategies to be very effective. In clinical practise, you want to try and find a strategy that doesn’t involve the woman having to calculate things for months.


Dr Katy Munro [00:17:27] Of course, as soon as they have slightly irregular periods, then you’re all over the place taking things on days and not knowing when to start or stop.


Dr Anne MacGregor [00:17:35] Absolutely. And I mean, we did some clinical trials a few years back that actually suggested that you could bridge this drop in oestrogen by using just oestrogen supplements around the time of the menstrual period. And in the clinical trial situation, they work quite effectively. But the downside was, is that you then created a delayed drop in oestrogen further into the next cycle, which then created another migraine. So again, although things can seem very effective in clinical trials, put them into the real life context, it becomes a different situation.


Dr Katy Munro [00:18:10] So what strategies have you found that are actually helpful?


Dr Anne MacGregor [00:18:13] I think certainly with women who have a mirena coil. I’ve a lovely girl I work with, a doctor I work with in Norway. She was doing her PhD on menstrual migraine and in Norway they all have mirenas very quickly after childbirth. It’s a really common strategy and she actually showed and published that in women who have the Mirena who become amenorrhoeic, they don’t have any bleeding, that that often improved their migraine because there are about 20% of women who have a Mirena who it also inhibits ovulation as well. And in that population it can work really well. So I think most of the strategies that I tend to recommend now tend to be ones that are also contraceptive and we’ll just try and treat and keep those ovaries quiet because they are the longer term, more effective strategies.


Dr Katy Munro [00:19:10] So we’ve heard several times from lectures and things we’ve been on and courses about using frovatriptan. So one of the longer acting triptans and again, but that’s a method where you have to count when your period is going to start, you have to start it two days before and carry on twice a day until day six. So again, does that go back to what you were saying about the difficulty of knowing exactly when to take it? Or do you find that is helpful in some people?


Dr Anne MacGregor [00:19:39] Yes, it can be helpful in some people. But I think, again, people get very fed up. They’re already fed up with their migraine. They’re fed up with their period. And to have to start calculating things then can often have a negative psychological effect on how that woman approaches her migraine as well. So yes, the frovatriptan can be very effective and in fact has been shown to be, in some cases, more effective than the non-steroidals and the oestrogen supplement strategies when they’ve done head to head comparisons of the three. And I think you can be looking at preventing an attack developing. So these preventative strategies are about using strategies that stop the migraine even beginning. And in that way, they can be effective. But you could also look at it say, well, actually, if I can’t get on top of it and I can’t calculate when it’s going to happen and sometimes it’s coming out of the blue, can I use that same strategy just to reduce the severity of the symptoms as I’m getting them? So, for example, with the frovatriptan. Why can’t women actually take it twice a day as treatment for the symptoms during her long duration menstrual attack.


Dr Katy Munro [00:20:58] And start it as soon as the period starts.


Dr Anne MacGregor [00:21:01] Well, as soon as she gets migraine starting.


Dr Katy Munro [00:21:04] Oh Okay.


Dr Anne MacGregor [00:21:04] Because you’re then not using it to prevent it but why can’t you use it as just a treatment strategy? So rather than waiting for the symptoms to relapse, as they will often do, why not just use it as a prophylactic, keep that migraine at bay once it’s started?


Dr Jessica Briscoe [00:21:23] I do find that the problem with that method is actually the amounts of frovatriptan that are in a box. A lot of doctors don’t like prescribing because it’s off licence. They say, ‘Oh, it’s not supposed to be given like this’. And they’ll often actually not give people enough. So I think it’s really an important point that if you are using that method for somebody to make sure they have enough to cover them for the whole period, because you would need more than six.


Dr Anne MacGregor [00:21:49] And you need to explain to the prescribing doctor exactly the relevance of that strategy because they immediately pick up on, ‘oh no, if they’re treating more than 2 to 3 days a month, then you know, they’re going to have medication overuse headache’. And you need to explain to them that these are recognised as being long duration attacks that are less responsive to treatment than attacks at other times of the cycle. And provided overall they are not taking triptans or more than nine days a month it’s a perfectly appropriate strategy. Because many people delay taking their triptans because they’re worried about not having enough supplies. And we know from clinical data evidence that if you don’t take that triptan as soon as you feel that migraine headache starting, then it’s not going to be as effective.


Dr Katy Munro [00:22:40] Yes, it’s something we hear a lot isn’t it. People know about medication overuse headache, and they’ve had it reinforced sometimes by GPs, sometimes it’s by pharmacists saying, ‘Oh, you’re taking too many’. And we go through quite a lot of explanation about days that you’re counting, not doses, and actually trying to hit it hard on day one and we’ve covered that in other podcast episodes a little bit, but I think it’s worth repeating, don’t you?


Dr Jessica Briscoe [00:23:06] Absolutely.


Dr Anne MacGregor [00:23:06] You can’t say it often enough.


Dr Katy Munro [00:23:08] And the other thing I think is just to clarify between the definition of menstrual migraine and menstrually related migraine. And as I understand it, one is where you have migraine just around periods, and that’s relatively rare in our experience because often people say, ‘well, it’s linked with my periods but I also get it other times in the month’. Am I right?


Dr Anne MacGregor [00:23:30] Yes. I mean I think one has to go back to that diagnostic criteria are there for research purposes only. They are not particularly relevant to clinical practise. When it comes to clinical practise, the only thing that is really relevant is, does the woman have attacks that are linked with their menstrual periods that are more likely to be occurring with menstruation than by chance? And if you get over that chance occurrence, then you can start looking at it as a specific entity. So from the clinical research that we’ve done, we know that in women who have menstrual attacks that are more likely to occur with menstruation than by chance, those are the ones that they are finding harder to treat. That are different from their non-menstrual attacks.


Dr Katy Munro [00:24:20] Right.


Dr Anne MacGregor [00:24:21] So as soon as you get women who they come along and they say, ‘you know, you can see that I’m getting these attacks every month with menstruation’, but they’re having a lot of attacks at other times of the cycle as well. Those are menstrual attacks. That’s not the same as menstrual migraine because menstrual attacks can just be chance.


Dr Katy Munro [00:24:39] A migraine happens to be around that time.


Dr Anne MacGregor [00:24:41] Because if you’re having a period that lasts for 5 to 6 days out of every 28, then there is quite high potential for them in somebody who has an attack every two weeks to just be by chance occurring with their periods and you just tackle their whole migraine. You don’t really need to focus on the menstrual attacks.


Dr Jessica Briscoe [00:25:00] I also remember hearing that menstrual migraine is more likely to be without aura as well. So the more prolonged severe attacks in the period, if it’s menstrual migraine, it’s much more likely to not have the aura. And I have seen a few patients who will say, ‘yes, I have other attacks at other times of the month, but the ones with my periods are much more severe. And actually, no, I never have the aura attacks too’. And I feel that they’re probably slightly different attacks. So I try to treat them slightly differently.


Dr Anne MacGregor [00:25:36] Yes, I think that that’s very true. Certainly in all the clinical trials we’ve done with women with menstrual migraine, even in women who have attacks with aura around their period, the menstrual migraine is typically without aura. And we see that overall falling levels of oestrogen seem to trigger migraine without aura, whereas high levels of oestrogen can trigger aura. So women, for example, who start taking the combined pill for the first time, higher levels of oestrogen, they might get aura for the first time. We’ve seen clinical trial data in women who become pregnant their high levels can suddenly trigger aura. When I first started working in a Menopause Clinic, we’d occasionally used to get women coming back because in those days we used to use a lot of oral oestrogen HRT, which gives you higher levels in the blood. And they would come back and say, ‘it’s funny, the first time I got these funny zigzag lines and my GP thought it was a stroke so stopped the HRT straight away and then I started getting all my hot flushes back again and I don’t know what to do so you know what’s going on here’. And we put them on transdermal oestrogen – body identical transdermal oestrogen, and their hot flushes would dissipate and they didn’t get the aura back again. So we know clinically these times of high oestrogen levels can provoke attacks of aura. Same when I was talking about puberty earlier, puberty and menopause, we see women and particularly those prone to migraine, getting much higher levels of oestrogen compared to women who are that same age who don’t have migraine.


Dr Jessica Briscoe [00:27:26] This feels like a good time to have a little breather. And if you’re enjoying this podcast, we thought we’d discuss how to spread the word. So we really want to make the podcast as popular as possible and spread more information about migraine to people who need it. If you are liking it, please go to your podcast platform and like and rate the podcast as much as you can. And if there is a possibility on the podcast platform that you use, please leave a review for us so that we can spread the word about how great the Head’s Up podcast is. Thank you.


Dr Katy Munro [00:28:07] I had a patient the other day who had had menstrual migraine and was taking the frovatriptan  through her periods and doing really well on it for a couple of years. And then she came back because things had kicked off and she was clearly now into the perimenopause. So that brings us on to that really tricky time when we see so many people.


Dr Anne MacGregor [00:28:33] Tell me about it, it is so, so tricky. And I’m still trying to work out how best to manage these women. So there is not a week goes by when I’m not still learning something about how to progress, because it always seemed logical that if you had a woman who started developing hot flushes and night sweats to use hormone replacement therapy because that managed the troughs and stops the dips and the changes that are causing all these symptoms and we know that you can use vasomotor symptoms as a predictor for menopausal migraine. There have been studies done that show the link.


Dr Jessica Briscoe [00:29:15] So just to confirm that the vasomotor symptoms tend to be the hot flushes.


Dr Anne MacGregor [00:29:19] Hot flushes and night sweats. Exactly. Now, here we have the problem with our migraine women, because, again, we know that women with migraine approaching the menopause seem to spike higher levels of oestrogen than women of the same age who don’t have migraine. Now, if you add HRT into that mix you can manage the troughs, so you stop the falling levels of oestrogen but you’re adding extra oestrogen into the mix on their already high oestrogen levels. And they come back with breast tenderness, often worsening headache, even if it’s not the migraine, fluid retention and so that perimenopause time becomes a really sticky issue as to how do you manage these symptoms. So we’re back to perimenopausal women without aura, otherwise fit and healthy, they can take the combined pill and that will act to manage vasomotor symptoms as well and things like the doubling up of the desogestrel pill if necessary with add back oestrogen off licence but safe.


Dr Katy Munro [00:30:37] It can work well, yeah, that’s interesting. And what about the other sort of things that we use for regular or high frequency migraines like tablet preventers, injections, Cefaly and even supplements like magnesium I’ve heard can be useful for menstrual migraine and sort of in the perimenopause. Do you feel there’s any place for those? Is there any one that you’ve got more favourite than the other?


Dr Anne MacGregor [00:31:01] Well, magnesium, there’s actually very little research done and it was actually an Italian gynaecologist, Fabio Facchinetti.


Dr Katy Munro [00:31:12] Lovely name.


Dr Anne MacGregor [00:31:12] It’s a wonderful name and he’s a wonderful guy. And he started looking at magnesium supplements essentially in women who had premenstrual symptoms as well. So magnesium tends to be quite useful for premenstrual symptoms. And there are actually some studies currently looking at a hormone analogue, sepranolone, which is effective for management of premenstrual symptoms and may be effective in the management of menstrual migraine. But clinical trials are underway at the moment, so that’s potentially, actually coming back to it, a third possible link that we may have with menstrual migraine.


Dr Katy Munro [00:31:52] People will want to know when will we know the results.


Dr Anne MacGregor [00:31:54] Probably not for a couple of years, I would have thought. The clinical trials have only just started and as you’re probably aware, trying to find numbers of women who actually do have menstrual migraine that you can put into a clinical trial context, it’s much harder doing the clinical trials. Because people have to be committed and in this case prepared to use injections frequently throughout their cycle as part of the treatment.


Dr Katy Munro [00:32:19] What about a hysterectomy? So I had a patient the other day saying, ‘Oh, I’ve got terrible migraines now I’m in my perimenopause and my friends’ it’s usually friends ‘have recommended that I should just have a hysterectomy and have my ovaries out.’


Dr Anne MacGregor [00:32:32] Yes. Thank you for asking that, because that is a problem that very frequently comes up, a question that gets asked. Unfortunately, the ovarian hormones in the ovaries are only the end organ. So actually the organ that is generating the problem is the hypothalamus.


Dr Katy Munro [00:32:51] In the brain.


Dr Anne MacGregor [00:32:51] In the brain. And I don’t think many people would want to have a hypothalamectomy because it certainly wouldn’t be good for their long term health. The other thing that we know that if women do nothing and it’s always important to bear in mind, that if women do nothing, their migraine is likely to improve in time.


Dr Katy Munro [00:33:11] Yes, there is always that hope isn’t there.


Dr Anne MacGregor [00:33:12] There is that hope. And we also need to remember that while migraine is a very seriously quality of life threatening condition, it is not a life threatening condition in its typical form. So we do need to be mindful of making sure that we are not storing up long term health consequences by virtue of the treatment that we give women. And there is clear evidence out there that retaining our ovaries are good for a woman’s long term health. That morbidity markedly increases in women who have their ovaries removed. Now, some women may need their ovaries removed for sound medical reasons, like ovarian cancer risk or diseased ovaries, for example. But in a woman who’s got healthy ovaries, there is no good reason to have those removed, particularly for migraine.


Dr Katy Munro [00:34:06] Yeah.


Dr Jessica Briscoe [00:34:07] And actually I see a lot of women who have had hysterectomies for other reasons, as you said, sound medical reasons and actually they can find that their migraine gets worse afterwards. So it wouldn’t necessarily be the fix the, you know, ‘just whip out my ovaries’ it wouldn’t necessarily be the big fix that everybody thinks it would be.


Dr Katy Munro [00:34:27] I did have one patient who had seen a gynaecologist about her migraines, and he had suggested that she had a chemical menopause and gave her a lot of medication to switch off her ovary function. And it didn’t work. Is that something you’ve come across too? I can’t remember the names of the medication.


Dr Anne MacGregor [00:34:54] It is common practise in gynaecology when you want to create a medical menopause you can you can use these particular hormones to do so. They’re usually given either as a nasal spray or as a monthly injection. The downside of them is that they give you or they give the woman massive hot flushes and night sweats so they can only be given in the context of add back hormone replacement therapy as well. But essentially, you can create exactly the same switching off the ovaries, keeping them quiet by things like continuous combined hormonal contraception and Depo-Provera. All you’re trying to do is keep the ovaries quiet and inactive. And it’s much nicer for women, for example, to take something like the combined pill or double desogestrel if they need to, that they feel more in control of themselves so that if they want to stop it, they can stop it straight away without all the other side effects that they’re getting with their gonadotropin-releasing hormone analogues.


Dr Katy Munro [00:35:54] The other group of people who it’s slightly difficult to know how to help with hormones are people with breast cancer risk, so a strong family history. I had somebody who knew that one member of her family had probably had breast cancer, but the rest was a bit hazy because she didn’t know her family history very well. Any comments on that?


Dr Anne MacGregor [00:36:17] That’s actually quite a highly specialist area, certainly at the menopause clinic I work in we see a lot of women who are living with breast cancer or we actually have a lot of women coming in who see the specialist because they are high risk for ovarian and breast cancer. They got the BRCA gene or a strong family history because some people can be at high risk even without having the gene, just from your family history. And there is some quite confusing data out there. So, for example, if we just consider something like combined hormonal contraception in women who are at high risk for breast cancer, they will also be at high risk for ovarian cancer. And the combined pill protects against ovarian cancer. And the data about the risk of breast cancer in women who are taking the combined pill is a little bit hazy. There is a slight increased risk. But actually things like lifestyle, like drinking more than two units of alcohol a week, not exercising and certainly having a BMI of over 30. Those are far more likely to increase your risk of breast cancer than actually taking the combined hormonal contraception or even HRT. So it’s important to put these things into context. And it’s again, coming back to how does the management of the migraine fit into all these issues that a woman is needing, what are her contraceptive needs? What are her wishes for pregnancy? How high is that risk? Is she under a family history unit? Is she, you know, under somebody else? Is she being treated for breast cancer? Because it then becomes a joint discussion with the team that she’s actually under.


Dr Katy Munro [00:38:07] Yeah.


Dr Anne MacGregor [00:38:09] So I’ve had some patients for example who have been treated for breast cancer who have chosen because their migraines are so bad that they want to be on combined hormonal contraception. They’re not at a point that they might want their ovaries and tubes removed for protection against ovarian cancer in the future. So it is very much a balance and an individual discussion.


Dr Katy Munro [00:38:33] All about risks and benefits and having a discussion with a specialist.


Dr Anne MacGregor [00:38:35] Providing the right information to the women to help them make the choice.


Dr Katy Munro [00:38:40] And we have come across a number of people who’ve been told, ‘oh, you can’t have HRT if you’ve had aura’. And I know that that’s not right. So would you like to explain why that is not right?


Dr Anne MacGregor [00:38:53] Yes. The very simple reason why that is not right is because in nearly all circumstances nowadays, we use body identical progesterone and body identical oestrogen for HRT.


Dr Katy Munro [00:39:07] So if you went to your GP and they prescribed HRT, would it automatically be body identical or do you have to specifically say, I want the body identical one?


Dr Anne MacGregor [00:39:17] Nearly always now oral oestrogen and the patches and the gels that we use all contain body identical estradiol. There are still some of the conjugated equine oestrogens around, but they are very rarely prescribed nowadays. So most people will be using the body identical oestrogen that is available on prescription from standardised clinical trials. You don’t have to go to people who prescribe body identical or bioidentical HRT.


Dr Katy Munro [00:39:52] So it’s not a wacky thing, it’s a normal standard thing.


Dr Anne MacGregor [00:39:55] It’s a normal standard thing prescription thing. And when it comes to the aura, the risks are only related to use of synthetic oestrogens that are themselves increasing the risk of stroke. So every single woman who takes a combined pill potentially double their risk of having a stroke because of the synthetic oestrogens in it. So we just don’t want to add extra factors to it. So, you know, that’s why we’re cautious about high blood pressure, about diabetes, all these other factors. Now, thinking about it the other way round with the HRT and the aura, because we’re giving natural body doses of natural body hormones, there is no more risk of the aura than if a woman is going through her natural menstrual cycle. And turning it around the other way we don’t switch off a woman’s natural menstrual cycle to reduce their risk associated with migraine aura so there is no concern.


Dr Katy Munro [00:40:55] So no worries about that.


Dr Anne MacGregor [00:40:56] No worries.


Dr Katy Munro [00:40:57] The other thing that’s been concerning some of our women who’ve been taking transdermal HRT patches is availability.


Dr Anne MacGregor [00:41:06] Yes. So the good news about that is the main patches that there was a shortage of, evorel, will be back on the market at the latest by February, but probably earlier. So anybody who wants to find out availability of HRT can look at the British Menopause Society and Women’s Health Concern website, and it’s regularly updated on the BMS website as to what’s available.


Dr Katy Munro [00:41:33] We’ll put a link to that in the blurb because I think that is a really helpful website and it has a great big chart of what to use if you can’t get hold of some things.


Dr Anne MacGregor [00:41:40] A lot about migraine and HRT and everything on that website as well.


Dr Katy Munro [00:41:43] The British Menopause Society website, go there.


Dr Jessica Briscoe [00:41:46] Very useful. I wanted to ask a question, actually. We have a few transgender patients who’ve actually found that their- I had one particular one whose migraine with aura really increased when they started taking a hormone-sort of.


Dr Katy Munro [00:42:04] Transitioning


Dr Jessica Briscoe [00:42:05] Transitioning. And I know you’ve looked into transgender patients and the effects of hormones on them. Is anything specific that sort of came out from that?


Dr Anne MacGregor [00:42:18] Very simply, we see that as they transition and using the oestrogen that actually changes the prevalence of migraine to the female three times more common. And the other way around is that you actually see that when testosterones are used, that that actually reduces the prevalence of migraine, not by using the testosterone so much, but probably by shutting down oestrogen. So one always has to think it’s not necessarily the drug or the hormone that you’re taking that is having the effect. It’s the knock on effect it’s having by removing something else or affecting something else. The important thing, I think, with trans-women is that they use transdermal oestrogen where possible or injectable oestrogens over and above the oral oestrogen because that reduces the metabolic load to the liver and therefore reduces the likelihood of aura being a problem.


Dr Jessica Briscoe [00:43:18] Okay.


Dr Katy Munro [00:43:18] So to clarify, transdermal oestrogen can be via a slow release patch that you stick on either twice a week or there is one that lasts for a whole week, or you can use an EstroGel or something like that. And those are the main forms of transdermal, through the skin oestrogen.


Dr Anne MacGregor [00:43:37] Exactly correct. And you can also get slow release injectable depo oestrogen as well. It’s not used in women, but sometimes it’s used in transitioning.


Dr Katy Munro [00:43:47] Yeah. One more thing.


Dr Jessica Briscoe [00:43:48] One more thing.


Dr Katy Munro [00:43:50] I was just wondering if you had any comments about the wonder new drugs that we’re hearing so much about the CGRP drugs and in particular related to hormone changes and women. I know at the moment a number of them are going through the process of being approved by NICE. Have you had any comments about using them with the kind of things you’re doing?


Dr Anne MacGregor [00:44:13] Unfortunately none of the pharmaceutical companies who have developed CGRP did any specific studies with menstrual migraine.


Dr Katy Munro [00:44:22] Right.


Dr Anne MacGregor [00:44:23] There are small poster data that have been presented. Essentially, I think that if you can reduce the frequency and severity of any number of migraine attacks, you make life more manageable for that individual. My experience has been very broad. They have been very effective for some people. Magical indeed, for some people. In exactly the same way we saw when the triptans first came out, they have changed people’s lives. In other people they haven’t been effective at all and in a very few number of people, it’s actually made the situation worse. So it’s important to just count, they are not the wonder drugs, they have a really important place. They have provided us with a new tool that we didn’t have before. Safety issues in the longer term will remain to be seen.


Dr Katy Munro [00:45:18] There’s a question mark isn’t there.


Dr Anne MacGregor [00:45:18] There is a question mark.


Dr Jessica Briscoe [00:45:20] Like with any new medication.


Dr Anne MacGregor [00:45:22]  You just haven’t had it around long enough to know.


Dr Katy Munro [00:45:25] So we, I think, would echo what you’ve said. We’ve seen some people that have had life changing results, some people who’ve had benefits, but it’s been sort of 50% reduction, which is very valuable in some and then other people, as you say, have really had not much benefit or have got worse or it’s worn off.


Dr Jessica Briscoe [00:45:44] Or even have sort of. I think it’s also important with any preventative to remember that your natural migraines cycle, so you have periods of time where it might be a bit worse and a bit better. That can still happen.


Dr Anne MacGregor [00:45:54] That’s really important. And I mean, in all the years that I’ve been working with migraine, you can often predict the time of year that somebody is going to contact you because they will go through even not necessarily every year and might be every couple of years or every three years that they will suddenly go through a bad patch. And then they’re absolutely fine for a while. And I think we really need to be careful when we’re thinking about preventive. If you have diary evidence from a patient over a number of years, you can actually say, just go back through your diaries you’ll remember you’ve been there before.


Dr Katy Munro [00:46:27] Yes.


Dr Anne MacGregor [00:46:27] And you didn’t have to do anything then. So maybe let’s just see how things go, because all drugs have side effects. So there is this, we do need to sometimes be careful about how quickly we jump in.


Dr Jessica Briscoe [00:46:41] I completely agree.


Dr Anne MacGregor [00:46:42] And there’s also the issue of how you manage different problems. So, you know, if the discussion we’ve been having has been about managing hormonal triggers, you will realise that we’re actually managing mechanisms that we know that are related to the specific development of that specific type of attack. Whereas in many of the standard migraine preventatives, rather than treating the trigger, we’re actually lowering the threshold to the migraine without actually managing the triggers. So it’s working again in a very different way.


Dr Jessica Briscoe [00:47:18] Yeah.


Dr Katy Munro [00:47:18] I think we try to work very holistically and talk about all the different lifestyle things that people can do because of course if you’re a perimenopausal women getting hot flushes, you’re not going to sleep very well. You might be at a time when your children are kind of going through university entrance or running your ragged or whatever it could be a number of other things contributing,.


Dr Anne MacGregor [00:47:41] Called life.


Dr Katy Munro [00:47:41] Not just the hormones. And I think we often say to people, you know, they say, ‘oh, I don’t know what it is’. And I say, it isn’t ‘it’, it’s ‘them’. It’s a number of things contributing.


Dr Anne MacGregor [00:47:51] And I think it is really necessary to think about how that person is coping as well, because sometimes they just get ground down by how they’re trying to deal with a migraine and they start feeling very negative about the outcomes because they don’t see light at the end of the tunnel. And psychological support can be really helpful in managing women, not just with migraine. We know that cognitive behavioural therapy, for example, has been shown to be very effective for managing menopause hot flushes because we know the power of the brain at making chemical changes. So the analogy I always use is if people think, you know, this psychological stuff, what’s that got to do with me? You know, I get physical symptoms. You just say to them, Well, if you get really anxious about something, you’re feeling really anxious. What happens to your body? And they go, well, you know, my heart starts racing, my hands start getting sweaty. There you go. You’ve changed the chemistry in your body by a psychological event, and you can use exactly the same to help change some of your brain chemistry, to better manage your migraine attacks or to better manage your hot flushes as well. So I think we often don’t use the brain chemistry enough, but then it’s harder to find the right people who will give that type of support. But a very underused management strategy.


Dr Katy Munro [00:49:14] We are very aware that people who are going through menopause are often feeling quite depressed and low in mood as well, and sometimes if it’s more episodic migraine. They seem to be low in mood during the migraine, but then absolutely fine in between. And I just have a sense that because the brain isn’t divided into neat sections, this is the mental health bit, this is the hormone bit.


Dr Anne MacGregor [00:49:35] Absolutely.


Dr Katy Munro [00:49:35]  It all overlaps, and so the same neurochemicals are influencing all of these things together. And I think if you can understand that then. The trouble is that a lot of people who don’t understand migraine will say, ‘oh, you’re probably stressed’. And I think that is partially stress can be very contributory, but it’s when people feel dismissed.


Dr Anne MacGregor [00:50:00] They just get told you’re a depressed menopausal woman.


Dr Katy Munro [00:50:03] Yes.


Dr Anne MacGregor [00:50:03] But I mean, we know that serotonin gets released from its storage site- serotonin is your happy hormone. And we know that it gets released from storage sites at the beginning of a migraine attack, during the premonitory stage before people have even got the headache. We see that drop in mood occurring. And if we collected everybody’s urine during a migraine attack, you’d see a rise in 5-HIAA, which is a breakdown product of serotonin. So their mood goes down, during a migraine attack as a symptom of it.


Dr Katy Munro [00:50:35] As a part of it, yeah.


Dr Anne MacGregor [00:50:36] And then, it improves.


Dr Katy Munro [00:50:37] And so venlafaxine and some of the anti-depressants that work for hot flushes, possibly, also we know that some of these NSRIs can be useful for migraine prevention. So would you ever use those?


Dr Anne MacGregor [00:50:51] Occasionally in women- I mean, oestrogen itself is an antidepressive hormone. We know that. So in women who can use oestrogen, it’s a positive thing to look at that. We see that in post-partum depression, for example, when oestrogen levels have really slumped and oestrogen has been shown in some women to be an effective therapy for the management of that type of depression. So we know there’s this link between hormones and depression as well, but there is a clear group of women who can’t take oestrogens for one reason or another who are still getting vasomotor symptoms. Maybe these women who’ve been treated for breast cancer, for example, who’ve got low mood, they’ve got migraine, they’ve got vasomotor symptoms, but they can’t take oestrogen. And we have seen in clinical trials that things like venlafaxine, things like citalopram, things like setraline can be useful for both. They’ve been shown in clinical trials to be useful for migraine and independently for management of hot flushes as well. So they can be used off licence for those particular situations. So we’re managing the serotonin, that’s managing the oestrogen that is working by secondary mechanism not a primary mechanism.


Dr Jessica Briscoe [00:51:55] Wonderful. I think that’s been a really useful discussion.


Dr Anne MacGregor [00:51:58] Must have got to the end of it by now.


Dr Katy Munro [00:52:03] I think we have. Thank you so much.


Dr Jessica Briscoe [00:52:04] Thank you for coming and talking to us.


Dr Anne MacGregor [00:52:05] Thanks for listening to me talk. You can see when i start I can’t stop.


Dr Katy Munro [00:52:09] Well I think we feel like that sometimes. You press our migraine button, we talk for hours, but our listeners are certainly going to be really, really interested in this episode. So thank you so much.


Dr Anne MacGregor [00:52:20] Thank you for giving me the opportunity.


Dr Jessica Briscoe [00:52:23] Thank you for listening. I hope you’ve enjoyed our podcast on hormones and migraine and for us to be able to keep doing this, we really need your donations. So if you could have a look at the blurb or on our social media sites, we’ve got a link to our Virgin Money Giving page.


Dr Jessica Briscoe [00:52:40] I hope you enjoyed our latest episode of our podcast. Our next episode, in two weeks time will be on History of Migraine.


Dr Katy Munro [00:52:47] Yes, we’re going to be having some special guests talking about how migraine has been perceived over the ages and also hopefully about where we might go forward with new treatments. So tune in for that one.


[00:53:02] You’ve been listening to the Heads Up podcast. If you want more information or have any comments, email us on info@NationalMigraineCentre.org.uk. Till next time.

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