#19. Female hormones and the immune system

Emily Kate Stephens (0:03): Welcome back. This week, I am joined by Abigail Goodship, a biomedical scientist and researcher at Imperial College. Today, we discuss the impact of female hormones on the conditions of Long Covid and ME/CFS. For the study we discuss, Abigail was actually working with the data gathered from Visible wearers, and I think it gives an exciting insight into the knowledge that can be gained from this type of research. Abigail Goodship, a very warm welcome to the Make Visible podcast. Thank you for joining me here today. Your primary area of research is looking at the way that the immune response affects the menstrual cycle, and you're looking at the ovarian hormones, but also you do some research into more of the pituitary hormones as well, and you have a real focus on the gender health gap, which I think is something that is very interesting in this space of complex chronic illness that we will talk about quite extensively today. First of all, tell me about your research to date and how you got to this point that you're working in this complex chronic illness space, and have identified this impact on and impact from menstrual hormones.

Abigail Goodship (2:01): Wow, that's a big question. I mean, we can go chronologically. In terms of sort of how I first got into hormones and women's health, that was during my undergraduate degree. I specialised in hormones, and at the time, I was getting tested for polycystic ovary syndrome, and it was that kind of sparked my interest in women's health because, of course, I'm learning about research. I was, oh, I want to read all these papers about it, and I was like, oh, there's not that much out there. There's actually not, you know, as many active research papers as that I would suggest. There's not kind of there's a lot that we don't understand. There's we're not great at diagnosing it. We're not great at coming up with treatment options for it. So yeah, I think the kind of injustice of it is really what then sparked my interest in women's health more broadly. And yeah, that's kind of what led me down that route in terms of complex illness. That was when my first kind of foray into that was with Visible, so I didn't have much experience before. But I think again, the kind of injustice side of thing is really what sparked my interest and passion in it because these are conditions that historically have been neglected, much like women's health, and so there's a lot that we don't understand about complex illnesses, and there's also a lot of unanswered questions. So, yeah, that's kind of what led me to choose doing that project and how I got into it. I

Emily Kate Stephens (3:32): Think it is an area massively overlooked. I think that it does feel in the past couple of years, and I don't know if it's actually from a lot of this research that's been going on, there does seem to be more prevalence in the media, and then more experts being added to GPs in terms of menstrual health, and particularly in terms of menopause. But I know from many of my conversations that it is an area that's much underrepresented, but much under researched in terms of the way that we look at illness, predominantly from quite a male lens, and don't ever look at the impacts of the hormonal, the menstrual cycle on many illnesses across the board, or indeed on most illnesses, we don't sort of reflect on it. Now, if we go back to prior to this research, there is understanding of the impact of menstrual hormones in a lot of autoimmune conditions. Can you tell me anything about that? We're sort of talking rheumatoid arthritis, lupus. Is that an area that you have worked in?

Abigail Goodship (4:49): It's not an area I've worked in, but it's an area that I hope to go forward in the future and work in. And I think in terms of what we know is that there does seem to be a relationship between hormones and symptoms of these autoimmune diseases, but it's off what we know so far as quite a complex picture. It's not very clear. It seems to be that in some autoimmune conditions, symptoms can say worsen during pregnancy, and others get better and similar across the menstrual cycle as well. I mean, if we take rheumatoid arthritis as an example, the that was quite similar to the findings that we found looking at the Visible data, where symptoms of rheumatoid arthritis tend to be worse in the perimenstrual period and then improve around ovulation. But in terms of pinpointing exactly how hormones affect autoimmune diseases. I think it's still quite poorly understood area. I think also because hormones are complicated. So if we take oestrogen for example, it can be pro-inflammatory, but it also can be anti-inflammatory depending on the concentration. So it can be yes. It's never going to be a simple answer of oh yes, this hormone will always do this thing. But I think with more research, we definitely can get a much clearer picture.

Emily Kate Stephens (6:12): But I reference those as maybe a kind of jumping off point from which there has already been research done that then took this idea. I think it was also very much a patient-reported idea in complex chronic illness, and specifically with this Visible study, you looked at Long Covid and ME/CFS. And quite interestingly, people report in the app whether they've got Long Covid, ME/CFS, or Long Covid and ME/CFS, and so there are blurred lines between the conditions in your data. But explain to me the starting point from which you approached this study. There are two kind of ways that you look at things, aren't there, in your research? But specifically in the study, which looks at the effect of ovarian hormones on these two conditions.

Abigail Goodship (7:11): Yeah, I mean, so in terms of the starting point, a lot of the kind of groundwork for the study had already been laid before I joined, but it really was patient-led in terms of the kind of how the study was set up. Is that patients came to us as scientists, you know, seem to be finding changes to my symptoms over the cycle? Is this a common experience? And oh well, there's no research on it. Let's do some research. So in kind of where I came in was after the data had already been collected. So I was brought in as look, we've got this amazing dataset from all of these women who've been tracking their symptoms and also their cycles. Do you want to analyse it? I was like, yes, to have this, you know, really rich data and also a really important question which hasn't been explored. So yeah, I came in. I hadn't done very much computational biology before. I had about six months' experience in coding, so it was very much a kind of figuring out as I went along. But I had really brilliant support from supervisors, and so yeah, just kind of started off cleaning the data. So where you've got perhaps missing days, getting rid of those. If there was anyone who wasn't in the eligibility criteria, filtering out those people. So say if someone was pregnant or breastfeeding, you're going to have a different hormonal profile. So yeah, cleaning the data, and then once I'd cleaned the data, then it was working out. Okay, so how do we investigate how symptoms change over the cycle? We've got data saying I'm on my period or I'm not on my period for each day, but then how do you go from I'm on my period, I'm not on my period to menstrual phases? So basically, kind of had to work back from okay, this individual was on their period this time. Let's kind of work backwards and figure out the phases.

Emily Kate Stephens (9:10): And presumably, actually, that's different for each person because although you have in the study sort of clearly identified parameters of what you're calling the mid luteal phase, and when you then go into the premenstrual two days, obviously every one cycle is a slightly different length, so there is variability within that. So adapting each of that cycle to the individual person,

Abigail Goodship (9:36): Yeah, absolutely. And so we know from various studies that the most variable phase of the cycle is the follicular phase, so that can be really short or really long depending on the person or kind of average.

Emily Kate Stephens (9:50): Could we just talk? I mean, some people might be aware of this, but could we just actually for our audience explain the phases? Yeah, and approximately what is happening to the hormones that we're talking about within each of those phases.

Abigail Goodship (10:07): Yeah, of course. Okay,

Emily Kate Stephens (10:09): So give me an overview.

Abigail Goodship (10:10): Yeah,

Emily Kate Stephens (10:11): Of these hormones. Yeah, and our cycles.

Abigail Goodship (10:15): Yeah. Okay. So everything is controlled in the brain. So you have part of your brain called the hypothalamus, which essentially it regulates a lot of different aspects of your body temperature, but also your hormones. And so, there's a hormone called gonadotrophin-releasing hormone, which essentially sets the kind of the beat of the menstrual cycle. That sort of sets the tempo of it because it is released from the hypothalamus, and then it acts on another part of your brain called the pituitary, which is a gland that makes hormones, and that triggers the release of two pituitary hormones. So you've got luteinizing hormone and follicle stimulating hormone, and these are released in kind of bursts, sort of pulses, and then your luteinizing hormone and your follicle-stimulating hormone act on the ovaries. So you've basically got this axis: you've got the hypothalamus, the pituitary, and then you've got the ovaries. And so then you've got your ovarian hormones, oestrogen and progesterone. And what happens during the menstrual cycle is that slowly. So starts off the beginning. You've just had your period, and you've got low levels of your ovarian hormones and also your pituitary hormones. But your luteinizing hormone starts to increase, and it's that increase in luteinizing hormone that triggers ovulation. So it's called the LH surge, and that then you've got your kind of follicle-stimulating hormone, which at the same time is acting on your ovary to stimulate the follicles. So follicle is basically a sac that contains the egg, and so those are triggered to grow and mature until this is in the lead up to ovulation.

Emily Kate Stephens (11:56): Exactly, menstruation is sort of approximately days one to seven. Then you go into this follicular phase.

Abigail Goodship (12:06): Yeah. So, and that's why it's called the follicular phase, is because it's when the follicle is growing and maturing. And once you've had ovulation, which is where the egg is released from the follicle, then the follicle turns into what we call the corpus luteum, and it basically yeah produces progesterone in a kind of imagine it sort of collapsing and shrivelling up, and that's your corpus luteum, and then that's why it's called the luteal phase after ovulation because you've got your corpus luteum producing progesterone.

Emily Kate Stephens (12:40): So then, at the beginning of that luteal phase, immediately after ovulation, that's when your progesterone starts to come up.

Abigail Goodship (12:47): Exactly, exactly. So your oestrogen is sort of rising during the follicular phase, but progesterone is still low. And then after ovulation, that's where you get the increase in progesterone. Yeah, and

Emily Kate Stephens (13:00): Then during that luteal phase, what happens to the levels of the progesterone and oestrogen?

Abigail Goodship (13:08): Yeah, so I mean, basically after ovulation, then oestrogen will start to drop. So yeah, oestrogen is dropping and progesterone is rising. Then sort of around sort of just before the period, that's when you start to get a drop in progesterone, and because progesterone, its role or one of its roles is to keep the lining of the womb sort of thick and spongy. So if an egg were to be fertilised and then implant, it would be able to implant really well. So basically, as when the progesterone starts to drop, that's when you start to get the bleed because that's where the lining of the womb then sheds.

Emily Kate Stephens (13:47): And then at that phase, that sort of late luteal phase, what has happened to the oestrogen?

Abigail Goodship (13:52): So oestrogen is basically dropping at that point,

Emily Kate Stephens (13:56): Still dropping.

Abigail Goodship (13:56): Yeah, yeah. So you can't. Well, you get a kind of after ovulation, oestrogen goes down, and then it starts to sort of rise a little bit, and then it goes down, but not as it's not a bigger rise as sort of happening during ovulation, if that makes sense.

Emily Kate Stephens (14:12): Yeah, and then from our understanding of that and the data that you gathered, can you tell me what happens to symptoms, and talk me through what symptoms? As in, I know everyone has very different symptom sets, but are there certain things that are more prevalent, certain things that are more affected, or hormone fluctuations that are more affected, that are more affecting of certain symptoms through those various phases.

Abigail Goodship (14:46): I should also say about the study a kind of a caveat is that we've done the work, but it's still in the process of being peer reviewed. But yeah, you can read it, and so we basically found that there was an association between how severe symptoms were and the menstrual cycle. So we looked at this in a number of different ways. So we did look at individual symptoms, and we looked at say migraines, for example. And migraines was really strongly associated with menstrual phase, which you might expect. So migraines were worse during menstruation and sort of in the premenstrual period, and they seemed to get better sort of around ovulation. And we also looked at we were kind of we knew okay people can have quite different symptoms, and some people have lots of different symptoms. How can we find a way to capture all of that information for an individual person on a given day? What can we use to represent how they're feeling? So we basically in the Visible app, then you can score symptoms on a scale from naught to three, and so we did this daily symptom score, which was essentially adding up all of the different individual symptom scores for a given day, basically as a measure to work out okay, not just the kind of how severe an individual symptom is, but the kind of collective burden of symptoms. Okay. So we also found the same pattern with when we looked at this daily symptom score, we found that symptoms were worse in the menstrual phase, and then seemed to get better, sort of around ovulation. So, that's sort of

Emily Kate Stephens (16:30): Across the board,

Abigail Goodship (16:32): Across the board. And we also looked at crashes as well, and saw the same thing. We can't say for certain, okay, this is caused by your menstrual cycle. We just see this pattern. There could be kind of underlying variables that are not accounted for. We call it confounding variables, but we did account for things like age. We accounted for disease type. So we tried to take the kind of things that could be kind of skewing the data into account, but at the same time, I yeah, it's difficult to say. Oh, this is causation. We can see a correlation, we see this association, but at the same time, I think it is really exciting that we see this pattern.

Emily Kate Stephens (17:15): Yeah, and you also in the study saw a very clear difference with people who were using hormonal contraception, and that's both oestrogen and progesterone combined pills, as in separate two different types. And you saw a different pattern amongst the people who were using that hormonal contraception. Can you tell me what you therefore saw, and if there was any difference between the oestrogen and the progesterone,

Abigail Goodship (17:45): Yeah. So we basically saw that symptoms on the whole were better or improved in women who were on combined contraception, so oestrogen and progesterone. We saw that symptoms in women who were on progesterone-only contraception was slightly better, but it wasn't significant. So we can't say for sure whether that was just something that happened by chance.

Emily Kate Stephens (18:12): Is that also? Could that also be to do with the fact that having that hormonal contraception, changing the balance of one, actually enables your body to change the balance of the other itself. Is that a sort of impact that it has?

Abigail Goodship (18:28): So, I mean, it does of course change the kind of ratios of oestrogen, progesterone in the body, and there is also quite a bit of variation depending on which contraception type you're on. On the combined pill, for example, you've got much higher concentrations of oestrogen and progesterone that you're taking compared to someone who's got a progesterone only coil.

Emily Kate Stephens (18:50): Now, I thought that was interesting because I thought that's what the study suggested at one point, but a progesterone coil does that not prevent menstrual cycle, or does that not stop the kind of cycle in the same way and stop the bleed? Were those people still included in your data?

Abigail Goodship (19:13): So yes. So for people who were on the hormonal coil, they would be included in the progesterone-only contraceptives category. We would have loved to split by contraception type. We just didn't have enough numbers in order to kind of make that split feasible. But yeah, it's a really good point in terms of so some women may find when they're on the hormonal coil that they don't have a period at all. Yeah, others may find that they have a kind of a period every 28 days, and it's quite regular. Others may find it's just very sporadic. So it can be different in different women, but yeah, it does affect your hormones, but it doesn't necessarily mean that you have. You may still be getting. So a cycle, a cyclical pattern of hormones. It just it's quite dependent on the individual. But yeah, no, it would be great to look at individual contraception types.

Emily Kate Stephens (20:11): Another question I have on that because you looked at the hormonal contraception, but a lot of people. I don't know if this is the case with ME as well, but a lot of people with Long Covid have been prescribed HRT. Now that is a lot of people say, well, that's because you were going into perimenopause anyway. I know a lot of people who got Long Covid who were, myself included, not showing any signs of perimenopause prior to getting Long Covid, massive shift in the menstrual cycle from the Covid, and subsequently, and also I know that you've looked a little bit into vaccines. I think people have had a big shift from the vaccines. How did you include HRT in your data or in your calculations in terms of people who are potentially smoothing out fluctuations in progesterone or oestrogen with HRT.

Abigail Goodship (21:11): So not in this study. No, we had an age range of 18 to 45, and yeah, you had one of the inclusion criteria was having a regular menstrual cycle, but we would love to do a study on HRT.

Emily Kate Stephens (21:24): But I had a regular menstrual cycle, super regular, but got put on

Abigail Goodship (21:30): Put on HRT

Emily Kate Stephens (21:32): For the hormonal. It didn't seem to impact my cycle, and I know people who are kind of 28 years old who have been prescribed HRT in Long Covid to try and smooth out, which is so interesting that then your data kind of corroborates that yes, the hormonal impact on the symptoms is significant. So to smooth out some of those fluctuations might actually have a considerable application to your symptoms.

Abigail Goodship (22:05): Yeah, no, that's super interesting. Can I ask? Is there a reason why HRT would be used rather than hormonal contraceptive? Or

Emily Kate Stephens (22:14): I know people that have been offered both from different people, and yeah, I can't. I can't speak medically on it. I just know that I was offered the HRT, and actually, I was still sick. I eventually had hormonal coil, and I'm so much less sick after having that. But I think that is to do primarily with blood loss because I was losing so much blood. So there are so many layers to this. But the thing is that there's something so fascinating about this fundamental point of the female body and the female hormones and the interplay of all of these things because I had horrendous anaemia for five years that I could not get rid of until I stopped bleeding to that extent, and that bleeding is because I am female and because I have this cycle. So yeah, I can't really talk medically on the HRT versus the hormonal contraception, but I do know that it seems to have an effect.

Abigail Goodship (23:22): Yeah, I mean, this is kind of this was our hypothesis going in: is that if you are able to kind of smooth some of those fluctuations of the hormones with hormonal contraception, is that something that's going to help symptoms? Yeah, and I mean, also we know that oestrogen can be protective in acute Covid. So

Emily Kate Stephens (23:41): Yeah, I read this.

Abigail Goodship (23:42): Yeah,

Emily Kate Stephens (23:43): How do you know that? Is that just in terms of the point at someone's cycle that they have got Covid, or how did you establish that?

Abigail Goodship (23:52): So that's actually from HRT data. So it's basically women who were on HRT with oestrogen as part of that HRT had lower hospital admissions with acute Covid-19 compared to those who weren't, which is really interesting. So that's kind of yeah, I guess that was part of our hypothesis going in, and we still don't know why we see lower symptoms in the women in our dataset who have yeah combined contraception. But yeah, could it be that oestrogen at a certain concentration is protective? Could it be that it's the smoothing out of the symptoms? Could it be something that we haven't accounted for? Maybe women who are feeling a bit better are the ones who are on contraception. So there's kind of there's all there's loads of different potential explanations. It's very much a kind of pilot study, but

Emily Kate Stephens (24:44): From which you can start doing more research. There are so many things that spring from this, and there are also so many elements that play into this. Two thirds of the women that you included in your cleaned data have not previously been pregnant or given birth, which is quite interesting in terms of demographic, because there are so many people who are kind of 35 to 50 who have Long Covid. Can you, from what you saw, interpret anything about the differences in terms of the effect of or on hormones of these conditions, if someone has been pregnant, because I've been fascinated about this from the beginning, was there a large proportion of people in that demographic affected because of having had children and the way that their hormones are then impacted by the virus, or is it because they have children that they have to deal with at home? Because I still maintain that there are a large proportion of people who are never able to recover fully from their Covid or whatever illness they had because they had small children. So you never have that break in the same way that a lot of primary healthcare workers were never able to take a break in Covid.

Abigail Goodship (26:08): No, I think that's a great question, and one I don't really have a good answer for. I mean, in terms of our models, we included whether or not the individual had a child and how many children they'd had as a factor. It didn't come out as significant in our models when we were looking at severity of symptoms, but that's not to say that yeah, it couldn't. And it also we were looking at severity of symptoms. We weren't looking at duration of how long someone had Long Covid or ME/CFS. So yeah, I think it's we don't know very much about it.

Emily Kate Stephens (26:42): Because there are some conditions for which a prior pregnancy is kind of protective, and there are some conditions for which it's really not. So I just wondered if there was any indication of the effect on the hormones of that.

Abigail Goodship (26:53): Yeah, yeah, no, it's so true. And because I mean, you also get so many other sort of physical changes during pregnancy as well, and changes to your immune system and all of that kind of there's lots that happens. The female body is amazing, isn't it? Of kind of, yeah, how it adapts and. But yeah, I think kind of Long Covid and pregnancy and ME/CFS and pregnancy is an area ripe for exploration and research.

Emily Kate Stephens (27:18): So let's look at it the other way around. What's the in other research of yours? What is the impact of infection? And perhaps you can talk about this in relation to specifically Covid, as I just touched on having that direct. I mean, I didn't have a period for nine weeks after I first had Covid, so it clearly had some huge impact on my hormonal cycle. What's your understanding of the impact of infection generally on the hormonal cycle?

Abigail Goodship (27:50): Yeah. So I mean, there have been studies that have looked at acute Covid infection and found that there are significant menstrual changes, which is not going to be a surprise, as you've just talked about, with personal experience with it, I have done some kind of literature searching and in this kind of area of infection. And I mean, there are there's a study on HIV infection affecting the menstrual cycle. But to be honest, there's not as much out there as you might think. I yeah, I did kind of struggle to find very much on infection, other than kind of these kind of isolated papers, and that's where really the pandemic has acted as a catalyst for research into the immune system and the menstrual cycle and hormones and how they interact with each other. It's kind of yeah really shone a spotlight on how little we know.

Emily Kate Stephens (28:41): I think that it's done that slightly across the board as well, because it's so many people that I've spoken to have said that we need to look at our bodies as one, our minds and our bodies as one whole entity, rather than looking at it as all individual parts. The interplay between the areas is so huge, even if you look at the interplay between the gut on the hormones, or the what's happened to the heart based on hormones or based on chemical levels in whatever. There's so much interplay, and I if we have to end up with these illnesses. I do hope at least there are these good things to come out of it in terms of the research.

Abigail Goodship (29:29): Yeah, yeah. It's my hope as well. There's so much kind of loss and difficulty during the pandemic, and as you say, still so many are suffering from its aftereffects. But yeah, if there are kind of good things that can come out and kind of generally new research and new revelations into how the body works, I think that is a good a bright spot in the yeah in the for sure.

Emily Kate Stephens (29:55): Can we talk a little about? Did you do some work into vaccine impact? Specifically in Covid,

Abigail Goodship (30:02): Yeah. So yeah, this was something that was sort of sparked by the pandemic. So I'm doing my PhD at the moment. My supervisor, Dr. Viki Male, she was one amongst others who looked at do Covid vaccines affect the menstrual cycle, and what these large scale studies have found is that there is a temporary impact, and it's yeah not anything to be too concerned about. On average, it was a cycle becoming a day longer after getting the Covid vaccine, and typically that would go away by the following cycle. Okay, so you know these are small effects, but they are significant. And so one of the kind of key areas of my PhD is to work out how this is happening. So why is it that vaccination would affect the menstrual cycle? Because yeah, so far we see okay, here's this significant effect, but we don't know how it's happening? There haven't been any kind of studies into the mechanism behind it.

Emily Kate Stephens (31:04): Okay, and so is that across the board in terms of vaccination in Covid, or was it specific types of vaccination?

Abigail Goodship (31:12): So it was across the board of different types of Covid. Also, we do see the same kind of cycle getting longer in other vaccines as well, so there was a study that came out earlier this year that found the same thing with flu vaccination. There's been a few studies from there's one from 1913 on typhoid and like HPV vaccine, which do seem to kind of show the same temporary impact on the menstrual cycle. So interesting, yeah. Because

Emily Kate Stephens (31:42): Isn't HPV vaccine given to children around the age of 13? So a lot of the time, those girls will just be entering their kind of early stages of menstruation.

Abigail Goodship (31:52): Absolutely, and so that's why it's really important for individuals who are going forward for the vaccines to know that this is a potential side effect, but also to be reassured that there haven't been any. I mean, at least with Covid vaccines, they haven't found any long-term fertility problems with the Covid vaccine. So it's not something to be like, oh no, I don't want to get it because then it's going to mess up my fertility in the long term. But more just, okay, this is normal. Like my cycle's a bit longer this month, or I've got slightly heavy. They've also found, as well as the longer cycles, heavier bleeding. So yeah, but I think also playing into that, I think it is important for us to know the science behind to understand the mechanism. Yeah. So yeah, and I think

Emily Kate Stephens (32:38): That's a big impact as well, isn't it that heavy bleeding is big impact from Covid as well as from the vaccine, and I think trying to understand why that is huge because with that understanding you can potentially mitigate some of these things. In terms of the, you touched on it before the way that oestrogen can impact symptoms. Does oestrogen also have a impact on our pain perception? Am I right in thinking? So, when you looked at the symptoms in some of these conditions, was it always pain symptoms, or was it across the board in terms of the symptoms that you don't necessarily associate with pain, heart palpitations, and things like that? I guess what I'm asking is: is oestrogen directly relating to pain the way that we interpret the symptom exacerbation?

Abigail Goodship (33:36): No, it's a good question.

Emily Kate Stephens (33:38): I don't know if there's too much data generally on that kind of impact of progesterone, but I know that the oestrogen does seem to have been cited as being potentially either reducing pain, maybe, and you mentioned before maybe pro-inflammatory, maybe anti-inflammatory. But I'm very interested to know whether it's the kind of is it to do with the way it changes the neurology, or is it I don't know a physical thing?

Abigail Goodship (34:07): So, in answer to your question, it wasn't just symptoms associated with pain. Okay, it was yes, there were some things associated with pain, but for example, I mean, so joint pain was significantly associated with changes over the menstrual cycle, but things like anxiety and depression also changed over the cycle as well. And in fact, so we looked at 36 different symptoms, and 25 out of the 36 showed this same pattern over the cycle. And the ones that didn't show that same pattern were altered taste, altered smell, and then we had, for example, constipation and diarrhoea showing the opposite pattern. If that makes sense, diarrhoea was worse and constipation was better at the same point in the cycle. Okay, as in they showed the inverse, which is what you would expect. So yeah, I think it's a good question about is I think yeah it is potential that oestrogen is kind of acting to reduce symptoms of pain but I think there's kind of more going on I mean we've talked a lot about the hormones but there's also menstruation is quite an inflammatory event as well so is there something to do with that is that a kind of is it the hormones? Is it the kind of increased inflammation? So

Emily Kate Stephens (35:24): That sort of immediately premenstrual, and then during the menstruation, the entire body is in an inflammatory state.

Abigail Goodship (35:32): Yeah, I mean, there's kind of debates as to how wide it is in the body versus is it more of a localised inflammation in the uterus? But they have found that the kind of markers of inflammation are higher in that phase.

Emily Kate Stephens (35:47): Wow! I mean, that I mean that's a really simple way to explain.

Abigail Goodship (35:51): But then at the same time, then the fact that we saw this association with hormonal contraception, perhaps that indicates the hormones play more of a role. But I think at this stage, it's kind of this study provokes more questions. There's kind of it's a great starting point, but there's still lots that we don't know.

Emily Kate Stephens (36:09): So talk to me about that in terms of where we should go. I'm not saying that you have to do it all yourself, but in terms of where we should go in exploring this further in ME/CFS, in Long Covid, in these complex chronic conditions, but more generally in terms of understanding female health, understanding how we need to look after ourselves and develop understanding of our bodies. Where should we go in terms of research? What's the next thing?

Abigail Goodship (36:48): A great question. I mean, I think it would be great to test out the hormonal contraception side of things in a larger cohort. I mean, because I mean that's a really if it is that contraception can help some people. It's cheap, widely accessible. For some people, it's not going to work because of the side effects. But others, if it does work, it's a really quick like improvement, basically. And similar, I think it is really important that we do a HRT study as well. And so I guess that's kind of more short term, but I think longer term. I think it is really important that we understand more about the female body and the immune system and how hormones affect the menstrual cycle and vice versa, because it impacts on so many different aspects of health. If you think about other diseases, knowing kind of the cycle, you should be accounting for that in your studies. I feel like it just it has such far-reaching implications. Even thinking about if you give a vaccine at a particular point in the cycle, is it more effective or less effective? That has big public health implications. There's lot. I feel I've I haven't done what you asked, which is tell you concisely what...

Emily Kate Stephens (38:06): I never asked for concisely. Yeah, I think it's fascinating area because I think as I actually said in one of my recent podcasts, one thing that chronic illness does do for you is it brings you much more into when you stop fighting it brings you much more into awareness of your own body and listening to your body. And I think as a society, one thing that we have really lost touch with is listening to our female bodies in terms of their actual natural cycles. And there is even with the HRT, there is so much about smoothing out the cycles, smoothing out the hormones, making everything normal, rather than embracing the fact that we are females and these are our cycles, and let's work with them. Now I know that you can't say that when you're talking about symptom exacerbation at certain times of the cycle, but at the same time, as human beings, one of the things from your study is that perhaps we can use this information to try and make lifestyle accommodations. That means that you're taking into account the fact that this part of your cycle is not going to be optimum for going out and doing this, that, and the other, try and actually work with your cycle to just make things a little bit easier. I know that's not what people want to hear. In terms of people want to feel better all the time, but if you could just be more gentle with yourself and try to accommodate the fact that when your hormones are dropping, you're going to feel worse. Give yourself until such time as we've got a solution. Give yourself some leeway in those days. Yeah, that was one of the. That your kind of things to come from the study.

Abigail Goodship (40:02): So true and kind of for every it may be that you start tracking your cycle and you actually you don't see for you personally there's much of a change but it may be that you do and if you do that could help and I think particularly for crashes if it's if so with our study we found that it was during the kind of just before the period, and then during the period where individuals were most vulnerable to crashing, it was like basically 45% lower crashes in the kind of ovulation phase compared to the menstrual phase, which is quite big. So if it was kind of maybe planning more demanding activities round that ovulation phase, where potentially maybe you're a little bit less vulnerable to crashing. I mean, I think it's very much each individual. You have to kind of, as you were saying, listen to your body and yeah, and don't let it define you either. If it's oh no, I've got a party during the bit where I'm going to be on my period, I shouldn't go. But just make accommodation for that.

Emily Kate Stephens (41:02): I think it's an interesting area as well. There, I think I'm obviously more aware of it because of my particular time of life. But there are so many more people now talking about it on social media and in the press about eating for your cycle, about exercising for your cycle, don't go out and do serious, heavy exercise at a specific point. At a certain point of your cycle, you're going to need to eat more carbohydrate and nurture your body. And I think anything that can raise awareness for the fact that we are females, we have these cycles, and let's start listening to them and working with them is a huge thing. Obviously, those of us who are really severely affected don't necessarily want them to be that prominent. But I love the way that we're starting to talk about it, and I love the fact that you chose to do this research specifically looking at the way it's impacting women.

Abigail Goodship (42:08): Yeah, I mean it. It really has been a privilege to work with the data, and I kind of feel like it was really right place, right time. And I was, oh, this is an amazing project. So yeah, if there's anyone who's listening who has contributed their data, really grateful. I think it's yeah, it's really brilliant, and I think it's kind of the more knowledge you have, the more it can kind of empower you. But at the same time, I think also see what all the stuff on social media take it with a little pinch of salt as well, and I definitely wouldn't want anyone to sort of feel limited by their cycle and not do things because I think yeah, there's kind of there's going to be so many other impacts as well, not just the cycle.

Emily Kate Stephens (42:52): You have done work previously looking at the effect of menopause on the immune system, or no? Was it

Abigail Goodship (43:03): So? I mean, I'm very early on in my career doing my PhD at the moment, but before my PhD, I had an internship at a startup which focused on holistic menopause. So what that meant was doing group consultations, but with a GP and with a nutritionist, and then with a psychologist as well. And so I did some research with them, looking at basically experiences of menopause, and you know how people felt about the idea of a group consultation. Okay. So, yeah, I mean that was eye opening as well because I hadn't really, I mean I wasn't taught much about menopause.

Emily Kate Stephens (43:41): I don't think anyone was.

Abigail Goodship (43:42): Yeah, yeah, but also to get to it. Yeah, but then the fact that I'd studied in my undergraduate degree endocrinology and hormones didn't have any lectures on menopause. Wow. I mean, I wonder if that's something that's changed now. I don't know, but that wasn't very long ago, and so yeah, that was eye opening itself, kind of doing that research and hearing about different people's experiences of menopause, and also opened up conversations in my own life as well with my mom, with other women around me, and I think it's really exciting how much menopause has been kind of raised awareness. There's just more talk about it, like Davina McCall's documentary. All of this stuff has kind of really opened up a conversation. I think, yeah, which is really good.

Emily Kate Stephens (44:30): I would be really interested to see data on the postmenopausal Long Covid ME/CFS because I know that, as we were saying, oestrogen has some protective effects. What happens when that whole cycle stops? There's so much information out there that if we start joining the dots on it, when we talk about looking at the chemistry and the biology of it, all together as one, that perhaps we could actually help people

Abigail Goodship (45:04): Translate this to people's lives to help people.

Emily Kate Stephens (45:07): Yeah, but I think that is something that you have done here. You've presented data, which enables people to see these are the connections. How can I take that information and potentially use that to help me in my life, yeah, fabulous. Well, thank you so much for the work that you and the team at Imperial are doing. All of these things are helping us to actually navigate these illnesses and to be able to live a little bit, live a little bit more. So, I really, really appreciate your work, and thank you so much for joining me today.

Abigail Goodship (45:41): Oh, thank you so much. It's been a joy to chat with you, and a real privilege to do this work. So, thank you for this. Thank you.

Emily Kate Stephens (45:54): I hope this gives you an insight into how the female cycle might be affecting these conditions, and possibly sparks some ideas in how we might be able to manage our conditions. This is a great example of how we can use wearable data to understand these conditions more fully, and hopefully develop strategies that enable us to improve. I look forward to joining you next time. Thank you for listening to Make Visible. Please do like, follow, or subscribe to listen to our next episode, where we'll be uncovering more insights into complex chronic illness. This was brought to you by the team at Visible, a group of scientists and engineers whose lives have been affected by energy-limiting health conditions. We're building wearable technology that's helping 100,000 people measure and manage their complex chronic illness. To find out more about what we're working on and how Visible could help you, visit our website at makevisible.com.

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