Ep. 226: Women and Neurological Disease: Are We Missing Sex-Specific Epidemiology?

00:00:00: Welcome to EA Uncast, your weekly source for education research and updates from the European Academy of Neurology.

00:00:15: Hello and welcome to EANcasts, Weekly Neurology.

00:00:19: My name is Kasia Szmiowska And I am a movement disorder neurologist working in Poland.

00:00:26: This month's topic is women and neurological diseases.

00:00:30: In today episode we will talk about Are We Missing Sex-Specific Epidemiology?

00:00:37: my guest Today Is Melinda Maghiari.

00:00:40: She is a professor at the University of Copenhagen.

00:00:44: She is also a director of Danish Multiple Sclerosis Registry.

00:00:49: Her research focuses on the changing epidemiology, gender differences and real-world evidence in MS And she serves on the EAN Neuroepidemiology and MS Scientific Panel.

00:01:03: Welcome Melinda!

00:01:04: Thank you so much for joining us today.

00:01:07: Thank you very much and thank you for inviting me.

00:01:10: That's great pleasure.

00:01:12: So to start, could you give us a brief overview of why sex differences in neurological diseases are still such an under-examined area of epidemiology and what we currently missing?

00:01:28: Yes.

00:01:29: And there are several reasons.

00:01:32: so in epidemiological studies historically Biological sex was only treated as a background characteristic, something we described in the first table because it made analysis simple.

00:01:46: We didn't study separately men and women And also some of data sources like clinical trials were rather underrepresented.

00:01:57: But women are not under represented on every neurological field.

00:02:02: The second difficulty, and I think we just clarified it right now that sex and gender are not interchangeable.

00:02:09: And i think i would focus in this podcast on the biological sex that includes chromosomes, hormones, reproductive biology and immune function.

00:02:18: Yeah!

00:02:19: That's great!

00:02:20: And drawing on your work with large-scale registries like Danish MS Registry how do sex differences in MS show up in practice?

00:02:31: in disease course, relapse patterns around pregnancy or long-term disability.

00:02:38: Thank you for asking me.

00:02:40: actually this was the topic that brought me into MS research because we have this MS registry which follows MS patients more than seven years and increased since the seventies.

00:02:56: So I started to research why women get more MS and then we find out that not only the incidence increasing, but it's also differences in disease presentation.

00:03:06: like women have more relapses while men have more progression And this happens until the age of fifty so until they age of menopause on till their age of immunosinances start.

00:03:21: So, therefore it really brings the focus back to hormonal factors and also emphasise that we have women with MS first woman who has MS.

00:03:34: Therefore you need to look at the disease on different lifespan of the MS women.

00:03:41: so yes in treatment response actually we don't know how women and men respond for disease modifying therapies.

00:03:51: We have a study now investigating it, I did the first study but i just included sex as a covariate instead of studying in different cohort.

00:04:01: So therefore it's a lot to study, we have to see how pregnancy influence the disease modifying therapy choice?

00:04:11: We have to look at how menopause symptoms overlap with MS symptoms.

00:04:16: and one interesting thing I want to tell you because we just find out that women In some countries in Europe including Denmark do not receive high efficacy disease modifying therapy in same extent and men.

00:04:32: And that's an interesting question because one reason of course is, until now women had to choose between being a mother or being treated with disease modifying.

00:04:43: So we were reluctant to describe the high efficacy therapy, but what I see even in my data is that all women receive less high efficacy.

00:04:54: We have to explore whether there's a neurologist behaviour or patient reluctancy because they are afraid of side effects.

00:05:04: So yes, we're running a European study to see whether there is equality in treatment for MS.

00:05:13: That's very interesting!

00:05:14: We saw the same pattern in Parkinson's disease which shows almost the opposite pattern with MS as it mainly affects men.

00:05:25: But in terms of device-aided therapies, we also see that women are under treated with those methods.

00:05:33: So it's interesting to see the same possible goes into MS fields right?

00:05:40: Yes and even though because MS is too third of the MS population for women as we have been increasing this awareness You know, I do not have that explanation.

00:05:53: so we really need to investigate.

00:05:55: That's

00:05:58: interesting!

00:05:58: Maybe

00:05:59: in other fields too like epilepsy and migraine or stroke... Yeah,

00:06:05: that's a very interesting point.

00:06:07: So stroke is something I would also ask you... ...I know this isn't your main field but the outcomes are often reported to be worse in women and sometimes also yeast factors like pregnancy proclampsia and hormone use.

00:06:25: so how well is currently reflected in Stroke Prevention Guideline?

00:06:31: Do we have such knowledge about it?

00:06:34: Yes, actually.

00:06:35: And I consulted a little bit with my stroke colleague and looked at the Danish guidelines.

00:06:40: so yes there is also an unawareness of women in stroke that starts already by not being aware about heart disease in women but already cardiovascular diseases.

00:06:57: If you ask me whether it's reported on the Danish guideline they are not.

00:07:02: The American stroke guidelines explicitly includes sex-specific consideration and there is some European guidelines also that include the sex specific considerations.

00:07:17: So because we know that pregnancy, hypertensive disorders of pregnancy increase the immediate stroke during pregnancy and postpartum There are also all other pregnancy complications, so the key idea is that obstetric history is a part of cardiovascular and neurological.

00:07:41: Another one's hormones contraceptives and venous thrombosis.

00:07:46: And everybody is discussing hormone replacement therapy in menopause and cardiovascular risk which based on old studies.

00:07:57: So I think we need to spread awareness and it not necessarily increases the risk of stroke and cardiovascular factors if is given earlier, during menopause and very controlled.

00:08:13: And another huge part of neurology is migraine, which would follow more patterns like the MS because it's three times more often in women.

00:08:27: So how much of that gap is hormonal versus driven by other biological or social factors?

00:08:37: In terms of that disease...

00:08:40: Migraine is much more visible, because hormones we know that explained a big part of female predominance.

00:08:48: Because before puberty the migraine prevalence is relatively similar in girls and boys like MS And then it's marked female predominant around puberty persists during reproductive years.

00:09:02: And we know this menstruational migraine that a rapid fall in estrogen before menstruation can trigger migraines, particularly that with aura.

00:09:17: But during pregnancy also it can change the migraine patterns and hormones interact with migraine biology because migraine is genetically influenced involving trigamino-neurovascular system and also some signaling molecules or the CGRP, and estrogen modulates this password.

00:09:40: However in migraine we should not look ahead away from social and behavioral factors because there are sleep disruption stress lots of other burden on women that can trigger a migraine And on other things, we may oversee the migraine in men because maybe women have a better health care seeking behavior when it comes to headache.

00:10:08: So there are some clinical consequences.

00:10:10: you have to ask about relation between attacks menstrual cycle contraception all these things.

00:10:18: but I could talk lot about it because my neighbor is the Danish headache clinic and I know they are running a study with an app where women report the menstrual cycles and they want to look at genetics, hormones in migraines.

00:10:34: So we know that hormones are important for migraine and again life span of women I think will get back there.

00:10:42: The woman is not just a woman it's a hormonal stage on different reproductive age

00:10:51: Exactly.

00:10:52: And especially those hormonal transitions like puberty, pregnancy and menopause.

00:10:58: do you think that we need more data on women in their lives?

00:11:08: Yes I think they need both hormonal data such as blood test biological data on an app and then we have big population-based data.

00:11:24: Yes, because it's also when even if you include women in clinical trials... We do not differentiate whether they are in the reproductive age or in menopause.

00:11:35: so I always say that sex and age is two things that could individualize treatment And usually just treat as one simple covariate.

00:11:49: Yeah, that's true.

00:11:51: And you already mentioned about the under-representation of women in neurological clinical trials and can you tell us some more?

00:12:01: So what do you think?

00:12:02: are the reasons why women are underrepresented?

00:12:08: There a historical reason but today we need to describe it more precisely.

00:12:15: Women were excluded of drug trials because they were considered capable of becoming pregnant.

00:12:22: So that has left gaps in pharmacology and safety, as a women may be very represented numerically in MS migrant Alzheimer's trials but they remain underrepresented on other trials like stroke and Parkinson's disease.

00:12:40: And when it is not balanced the sexist then Analysis, sex stratified analysis is on the power.

00:12:48: And for example this why we can't see a difference between men and women in MS because there are very few men's.

00:12:56: but now they're talking about why women underrepresented.

00:13:00: so I think maybe it may be more prone to say yes to attire less burdened also with social things and family things.

00:13:10: And again, maybe they are offered more often a trial like women... They're offering better treatments than women?

00:13:19: So I was wondering whether the care partner matters.

00:13:23: so if you were woman without disease would it be more likely that you will join clinical trial because your career partner Advise you to do that and another way around.

00:13:37: Do you see feel that care partner?

00:13:39: Matters in that?

00:13:41: I think so, I say exactly.

00:13:42: there is a. yeah i totally forget That.

00:13:44: yet of course if it's a woman they are more caring.

00:13:47: They're most socialized to care.

00:13:50: So they would also give better support for a man too To participate in a clinical trial.

00:13:56: while women In some parts any most of the parts in Europe and the world are socialized to take care of other people, so they maybe do not take that time for themselves to participate in clinical trials.

00:14:11: And as a neuroepidemiologist what would you think about the outcomes?

00:14:17: Are there any specific sex-dependent outcomes?

00:14:22: I

00:14:26: think when we let's take out drugs, the pharmacodynamic pharmacovigilance.

00:14:32: We treat women and men with the same dose as a terastandard dose.

00:14:38: there are different.

00:14:40: The weight is different.

00:14:42: sometimes you also wonder in MS that they give the same those of anti-city treatment for a woman or fifty kilo and for our man four hundred something kilo?

00:14:55: And It's a problem.

00:14:58: Therefore, we also say women report more side effects but maybe they are overdosed with some of the drugs.

00:15:07: so I think an individual dose should be desirable and also that drug metabolism is... So treatment response but also the presentation of a disease.

00:15:21: We may always see a disease characteristic in men and women because maybe MS, Parkinson's or other diseases just have different phenotypes for men and woman.

00:15:34: When we study neurology like one sex...

00:15:41: Exactly, exactly.

00:15:43: So you already answered my question about looking ahead and how we could do more sex-specific epidemiological perspective with the precision medicine?

00:15:56: We should look at not only the sex but maybe both ways then adjust the dosing.

00:16:03: I also wonder What would be your advice to the one thing that you could share with the clinicians, who are listening us today?

00:16:13: To take away and start applying in their own practice.

00:16:18: In clinical practices but also research practices.

00:16:22: what do we recommend?

00:16:24: I think for research practices they have to collect data.

00:16:32: Data can generate evidence and in this artificial intelligence era, different kinds of data are doing with an app.

00:16:41: With variable devices registries electronic record minus you have some data but also to be aware that the evidence there is difference.

00:16:52: when I prepared for these podcasts i learned a lot about other diseases where For example, in Parkinson's disease about that is just the opposite.

00:17:04: That men have a higher prevalence but also different epidemiological estimates in different countries.

00:17:12: so I think we would say be very up to date with evidence and just common sense.

00:17:22: treat women differently because they are not the same and they have different hormonal profiles.

00:17:30: And look at the women, why she is taking contraceptive when she needs family planning?

00:17:40: Already a perimenopause or already a woman of the middle of forties?

00:17:45: be aware of symptoms.

00:17:46: don't mistake it with something else.

00:17:49: use hormone replacement therapy if needed because it may prevent some cardiovascular problems and some of the neurological diseases, also postmenopausal.

00:18:00: And give more awareness when we treat men and women differently!

00:18:06: Oh that's a great takeaway.

00:18:08: thank you so much Melinda.

00:18:10: it was such pleasure to hear all your insights about the sex differences.

00:18:16: Thank

00:18:18: You So Much.

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