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Women's Periodontal Health in Menopause with Drs. Nil Yakar and Alpdogan Kantarci
96 Plays2 days ago
In this episode, Dr. Effie Ioannidou interviews Drs. Nil Yakar and Alpdogan Kantarci on their study looking at subgingival microbial levels in pre- and postmenopausal women. Does menopause alter the subgingival microbial balance in women? Listen for a fascinating discussion!
Read the full article here. https://aap.onlinelibrary.wiley.com/doi/10.1002/JPER.24-0267
This podcast is produced by the American Academy of Periodontology. To learn more visit perio.org.
The views expressed in this episode are those of the participants and not necessarily those of the AAP.
Music Credit: Groove Nation by OctoSound
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Transcript
Introduction to 'Probing Perio' Podcast
00:00:00
Speaker
Whether you're in training, in practice, or in research, the Journal of Periodontology and Clinical Advances in Periodontics have something new for you. Hello everyone, I'm Dr. F.U.
00:00:12
Speaker
Anidou and I'm the Editor-in-Chief of the Journal of Periodontology and Clinical Advances in Periodontics. Tune with our team to Probing Perio, the podcast that aims to discuss advances and innovation in periodontology and implantology.
00:00:35
Speaker
Hello everybody, we are back here with Probing Perio.
Focus on Women's Periodontal Health and Menopause
00:00:40
Speaker
ah Today we are going to discuss a really important and very understudied topic, ah both in oral health and I guess in general health too.
00:00:52
Speaker
So we will focus on women's period on the health. My name is Dr. Efio Anidou. I'm the editor-in-chief of the Journal of Periodontology and the Clinical Advances in Periodontics. I'm here with you at perio a Probing Perio, the podcast that explores and dives into clinical and translational work in periodontology and implant dentistry.
00:01:13
Speaker
So hi, everybody. Hi, friends. If you enjoy pay but Probing Perio, please help us by rating the podcast on Apple Podcasts, Spotify, or wherever you listen.
00:01:25
Speaker
And leave us a review. We we read these reviews. we We appreciate your feedback. And we try to adjust our programming. So today we will be talking about menopause.
00:01:39
Speaker
I was just, I'm super excited to have our guest with us today. And just to give a little bit of and an idea why this topic is important.
00:01:51
Speaker
We know that half of the world's population, the women's population, would deal with this condition at some point in their life. ah Epidemiologically, we also know that approximately 1.3 million women every year in the U.S. end their menopause. So it's a significant number of people, right?
00:02:10
Speaker
So we are going to talk about them women in pre- and post-menopause and their periodontal
Introduction of Guests: Dr. Alp Kadarski and Dr. Neil Yaccar
00:02:17
Speaker
health. And what amazing guests we have with us today. First of all, my good friend, Dr. Alp Kadarski from the University of Minnesota.
00:02:28
Speaker
ah Welcome, Alp, to Probing Perio. And then Dr. Neil Yaccar, who is a postdoc, used to be a PhD student in Alps Lab, and now a postdoc at Forsyth. But like why don't I let you guys introduce yourself a little bit more and talk a little bit about your career? Actually, if we start talking about your careers together,
00:02:55
Speaker
I'm pretty sure we will pass the half hour that we are supposed to be talking here on the podcast. But it's interesting for our audience to learn more about your career trajectory.
00:03:10
Speaker
So, Alp. Thank care of you, Effie. It's a pleasure and honor to be here. So as a is' not only a good collaborator, we're also good friends and everything runs in good friendship as well.
00:03:22
Speaker
That's right. My name is Alcantarci. I used to be at Foresight Institute for 15 years. And before that, I was trained at Istanbul University and Boston University. i served as a joint faculty at Harvard.
00:03:35
Speaker
And recently, I accepted a job at the University of Minnesota. I'm a periodontist, obviously, and but I'm the head of a very large department of developmental and surgical science at the University of Minnesota Dental School.
00:03:46
Speaker
And I have my research lab, and we're still running a lot of research projects here. I'm a clinician. and the scientists and I love being an educator as well and being friends with really top educators, clinicians, scientists like yourself. if Thank you so much for giving us the opportunity share our work with you.
00:04:06
Speaker
Of course, of course. Welcome. And Neil, so nice to have you, a fresh face. that so That was a great surprise to have you with us today as the first author of the study, of course.
Guests' Backgrounds and Research Contributions
00:04:18
Speaker
Thank you. I'm also very happy to be here and talk with you. And I'm Nelia Carr. I'm a periodontist as well, and I have a PhD in microbiology.
00:04:29
Speaker
ah In the last year of my PhD program in 2023, and I joined Dr. Cantarchi's lab at the ADA Foresight Institute. Here I completed the analysis of my of the study we will discuss today.
00:04:45
Speaker
And right now I'm a postdoctoral fellow at the ADA Foresight and doing research on the mechanisms that contribute to periodontal disease ah progression after menopause.
00:04:59
Speaker
That's so great. How do you enjoy the transition from PhD to postdoc? ah Foresight is a very good place to be. um I really like it here. The research opportunities are very good.
00:05:14
Speaker
And you are originally from, I assume from the accent, or originally from Turkey, right? Yes, that's correct. I'm from Turkey. And you did your basic dental degree there?
00:05:27
Speaker
Yes, all my trainings are from Turkey. Okay, that's great. It's a long, long distance, right? ah Yes, it's ah almost 10 hours.
00:05:39
Speaker
Yes, it's quite a bit. I know. It's important for us to highlight ah here, to take the opportunity and highlight how important it is for you know what ah the and the moreoid motivation that shows from your ah part to finish the NL school there, come here for your graduate studies, be committed in research, be committed in advancing research, right? So it's really important for us, to any opportunity to we have to highlight the contributions of our international partners and international students and how eventually they contribute not only to our research but also to our educational programs. I just i think it's important for us to bring this up and discuss about it, every opportunity we have. will We take it for granted and I think ah many times ah the public and our audience, even practicing dentists, don't really understand the magnitude of this.
00:06:34
Speaker
Yes, yes, I really appreciate that you emphasized that. um And ah if you'd like me to give a bit of background about how I started
Motivation and Initial Studies on Menopause and Periodontal Health
00:06:45
Speaker
this. Yes, would love to. Yes, please so you got we began studying on menopause ah in 2019 in collaboration with Dr. Gülnir Emingil at the Egge University and Dr. Nagyam Bostancat Karolinska Institute.
00:07:01
Speaker
And at that time, we had another cohort. of Our first cohort ah focused on inflammatory mediators in postmenopausal women. And in the second cohort with Dr. Kantarje, we focused on microbiome aspect.
00:07:18
Speaker
asking whether the subjunctural microbiome because it becomes more dysbiotic after menopause. And um I acknowledge the world but value of this subject because menopause is associated with widespread changes in female's body and ah periodontal health is well known to be affected by female hormones.
00:07:44
Speaker
And um i I feel really lucky that I've been able to ah work with such great mentors throughout my career so far.
00:07:56
Speaker
So tell me a little bit. First of all, like, ah you know, what was that that click this idea to the the team, you think? Like, did you guys wake up on day and you said, oh, women go on menopause. Let's to see what's going on. How did this come up?
00:08:13
Speaker
I mean, this is this is really something that stemmed from Neil's curiosity as a PhD project there. and but She was also working with two of my really good colleagues. One of them is a microbiologist and the other one is a periodontist from Izmir.
00:08:29
Speaker
And they were fantastic scientists. So I think that's one of the, I mean, the reason why I wanted Miu to be here was because this was really her idea from the start. So she can come up with that.
00:08:40
Speaker
But as you very much alluded at the beginning, Gaffee, is that, I mean, do it there are two angles on this. Number one, half of the world population is going through this. if You cannot ignore this.
00:08:51
Speaker
And the second part is that you don't know enough about this in terms of the periodontal conditions, especially in the aging populations, because all of us want to age healthier.
00:09:04
Speaker
And that's a really interesting angle to study these systemic conditions, not the disease, obviously. It's a systemic condition, which is part of our physiology.
Role of Periodontists and Research Challenges
00:09:14
Speaker
But really bring us to understanding about what's really going on, assess that, and then start thinking about how we can age women postmenopausally healthier and then really create ah better lives for that. And of course, being a periodontist is a very critical arm of this entire equation because our job is to prevent.
00:09:36
Speaker
diseases, prevent any mishaps happening for this. And that's really the reason why i was interested in Neil's idea, and I was very supportable for this from the get-go. Yeah, that's a very, very well said. What about you, Neil? Because you are fairly young, obviously it's not personal experience, I assume, but what does that the attract you towards ah um menopause? i I thought that in my introduction, as Alp mentioned, I just wanted to make a point that...
00:10:07
Speaker
yeah You know, in in the mind of a lot of practitioners and a lot of researchers, you know, that's a women's issue. So, you know, it's it's fine. It's a women's issue.
00:10:18
Speaker
So we kind of has been understudied because there are so many assumptions around the ah yeah usually topics that the um that have to do with women's health.
00:10:28
Speaker
So, um so I thought that I wanted to put it in a perspective of numbers and, and, you know, the half of the world's population, 1.3 million women in the U S 50 million right now being on menopause approximately. um And again, these are American numbers. um and this This shows us that this is a significant population and it cannot we cannot afford to have these women understudied, right?
00:10:54
Speaker
So tell me what was in the in your mind when you started collaborating with others and with Nagy, you know, Nagy and and nain Karolinska, your collaborators in ah Turkey.
00:11:07
Speaker
What came into your mind? How did this hypothesis ah come together?
Impact of Menopause on Periodontitis Severity
00:11:15
Speaker
In the literature, there is enough epidemiological evidence showing that when there is menopause, then there's periodontitis.
00:11:25
Speaker
Menopause is related with increased attachment loss and increased periodontitis severity. ah although it's not considered as a risk factor for the onset of the disease.
00:11:36
Speaker
But ah the contributors of this situation are not well defined. And periodontitis incidence peaks before 40 years of age, and menopause comes after 45 years of age, right?
00:11:52
Speaker
This means many women with periodontitis enter menopause ah with chronic inflammation they in their mouth. And this may have a bidirectional interaction, ah meaning that menopause may influence the course of periodontitis, and in turn, periodontitis may relate to systemic comorbidities related to menopause.
00:12:18
Speaker
And I found this very interesting, and this I believe this interaction need to be further investigated. So, um our a couple of clinical studies, observational studies we did were investigating the microbiome and biomarker ah perspective of this situation, and we still keep exploring on this with the animal, including the animal models.
00:12:50
Speaker
right now. Yeah, that's that's that's great. And tell me like about the study, like how many, ah so people and our audience can really understand the magnitude, right? How many people did you have and how easy it was to collaborate with other sites outside the US? s So we collected all of our samples in Turkey and in both cohorts in total, we had over 300 women.
00:13:19
Speaker
Oh, that's great. um Yes, yes. And we analyzed our samples either in the a at the ADA Foresight Institute or at the Karolinska Institute.
00:13:34
Speaker
and So the practicality, so the samples would be ah frozen and shipped, right? Yes, yes, that's yeah that's that's right. they They have been shipped ah frozen.
00:13:47
Speaker
on dry ice. That's great. and oh my God. I've been analyzed by myself. I'm sure it's a logistical nightmare, right?
00:13:58
Speaker
ah Yeah, there there have been a lot of ah back and forth emailings. ah and depend ah you you To depend your research on ah shipping, that's you know whenever this happens to me, I feel like extremely stressed because if something goes wrong with it, yeah, yeah.
00:14:19
Speaker
yeah yeah Yeah, I don't want to even even recall that time. That was a quite a bit of stress after I reached their point.
00:14:29
Speaker
So tell us a little bit, Neil or Alp, or both. um any What are the major findings of the study?
Research Findings on Postmenopausal Periodontal Health
00:14:38
Speaker
And was there anything that really surprised you or something you didn't expect or something that, you know, any numbers that you were like, oh, that's interesting.
00:14:47
Speaker
Mm-hmm. there were There were quite surprising results out of this, but I will let Neil to speak about them because the hypothesis was great, but then the data was even greater.
00:15:00
Speaker
So, um postmenopausal women had higher numbers of missing teeth and ah higher probing depth, which was ah something we we expected.
00:15:13
Speaker
ah ah And not surprisingly, again, periodontitis was the main influence on both inflammatory marker levels and microbiome environment characteristics.
00:15:24
Speaker
ah But importantly, menopause was not associated with with increased dysbiotic tendency. And this is i this was important to show because all our gold standard therapies in periodontitis are primarily antimicrobial.
00:15:45
Speaker
and An interesting finding was that Streptococcus constellatus, this is a bacterium associated with pathogenicity and um and had documented in some brain abscess cases ah relate of odontogenic origin.
00:16:00
Speaker
ah This bacterium was correlated with serum oestradiol levels in premenopausal women. so These are the main points, more most critical points of our studies so far.
00:16:16
Speaker
And um all this suggests that postmenopausal women in postmenopausal periodontitis, host response ah is the ah main contributor. And um we keep working on finding out the sources of the susceptibility in this woman.
00:16:39
Speaker
I mean, one of the things that, I mean, Neil very elegantly summarized what the results were. But one of the things that were really interesting, which is something that we're seeing also in non-menopause groups as well,
00:16:52
Speaker
that the host response as she alluded at the last point completely determines what type of microbial ah species are going to be really colonizing the oral cavity this is not as simple as saying that one hormone does this or one lack of hormone one reduction of hormone is doing it it's really what the hormones are doing to our system so if you think about this and then that's reason why i think this project is very interesting is that many of the things that we're seeing in this particular population may have started earlier than what we actually are seeing.
Hormones, Host Response, and Microbial Colonization
00:17:29
Speaker
So it was cross-section and there was a longitudinal arm of this study. But in both arms, what we've seen is that, which is something that we've been suspecting in the field of aging, obviously, many of the things that have happened to us in later ages really start much earlier in our like lives, in our basically livelihoods.
00:17:50
Speaker
And this is exactly another affirmation of this because as opposed to us hypothesizing there was a linear relationship, there was a much more complex relationship between the microbial ah populations and then the state of menopause or premenopause.
00:18:05
Speaker
It wasn't this clear as saying that, well, if you get menopause, you're going to get gum disease or vice versa type of this. This is what the epidemiology data is showing. However, when you dig deeper, it looks like that this is going to be at least certain responders versus non-responders. And these may be completely different.
00:18:24
Speaker
They discriminated from each other based on the host response. and of course based on the microbial communities as well. So there's a lot of work that Neel is doing right now to understand the mechanism, biological mechanisms underlying this source, how the contribution of inflammation, what the contribution of hormones, how the estradiol levels are actually living, and that's what the next paper she's putting together actually right now.
00:18:49
Speaker
So when you look at particularly at the red complex, what are your findings? Because I know you spoke about diversity, but if we focus into the you know the but that three bacteria that ah really matter in periodontitis or with things they do. ah ah whats What's happening? yeah that If we look at the Keystone PIDG Valleys, ah what are your findings? Can you speak about this a little bit more? Because I know you have very nice graphical representation in the in the paper.
00:19:27
Speaker
And I don't want people to go need to go to try to understand the graphs. Give us a gist. Yeah, one of the earliest papers on the hormone and hormones and bacterium bacteria relationship ah is ah Dr. Kornmann's.
00:19:43
Speaker
It was back today, that like 1982, if I'm not wrong. And what they have shown is that estradiol is a growth factor on ah but like black pigmented bacteroiders, which includes provotella and also porphyromona species.
00:20:03
Speaker
And um actually, ah ah sure not lack of ostrodil, but ostrodil itself ah is a promoter of this ah rat co complex species. And this so has also been shown in pregnancy gingivitis and ah by the studies of Dr. Gursoy from Turku University in Finland.
00:20:28
Speaker
And actually, that's why our results was not so too surprising for us. um Our perspective in our study was looking at the subgingival ecology rather rather than ah individual bacterial levels because we see a a clinical scene ah which ah is more severe attachment loss in postmenopausal women. and Our goal in this particular study was to um investigate the role of microbiome ecology.
00:21:01
Speaker
and ah Here, our critical finding was that it's not the microbiome that is changing. And this is ah also ah clinical step for the investigation of the host factors and also maybe for our future ah treatment ah approaches.
00:21:27
Speaker
So ah in summary, ah to and to answer your question, ah we do not see an increase in pathogenic species related with postmenopausal transitions.
00:21:41
Speaker
and Actually, in reverse, and pregnancy and the situations where um characterized with ah increased oestrodial levels are related with their increase clinically.
00:21:56
Speaker
And one thing to add to Neil on this one is really... We also verified two different technologies using each other. And one of them was classical using the checkerboard, checkerboard, DNA analysis that Sokransky has developed, which is much more of a targeted species detection.
00:22:16
Speaker
And then when we first started, actually, i like very strong minded students and colleagues to work with
Methodologies and Hormonal Research Considerations
00:22:24
Speaker
me. Neil and I had a lot of debate about this and But then the next level was to look at the single sequencing for the completely understanding what the microbiome composition is without a bias on this one.
00:22:37
Speaker
And out of all of these methods, I think 19 of them, if I'm not mistaken, confirmed with each other's rates and ratios and relative abundance, which was really interesting.
00:22:49
Speaker
So it's not only the maybe it's not the red complex bacteria maybe it's not like the classical species that we've seen changing in response to periodontal disease and menopause but there are also new candidates that can really be changing this continuous changing of ecology between the host and the microbial complexes so that's a really another innovation in this paper because it was really looking at the same question from complete different angles compete different methodologies and then try to find an answer for new targets of
00:23:21
Speaker
ah disease and infection as well. This is great analysis from both of you and I appreciate this. ah No, I think the paper is very interesting. I um am also very interested in this population. I'm um in general ah interested in women's health and I especially as as it relates to oral health.
00:23:42
Speaker
ah When I um look at the paper and i' I do appreciate the work, I really like that you ah you know As both of you pointed out, it's really multidimensional kind of approach. like You looked at many different, you know at least bidimensional approach. You look at the different different aspects of the question.
00:24:04
Speaker
um I cannot help it, though, paying attention to every detail. so i and and And from this comment that I make, I'm... kindly make i just want to also expand it to your future directions so when you look at the estradiol levels right in the pre-menopausal women which you um expect that will be high and they are right they are higher than the post-menopausal but the range is like so wide that there is an overlap if you see that the levels range from 88 to 301, right? low to high.
00:24:43
Speaker
which is like low to sky high ah So what I was thinking when I read this is, okay, so there is a variability, obviously, in the premenopausal women. And then perhaps this has to do with the time of the cycle that where these women you know were examined and the serum was examined. So yeah depending on what where you are standing in the fluctuating estradiol level um during the month, maybe some women had higher or lower. So you know that's something that one can think about.
00:25:17
Speaker
But more importantly, what I was thinking is, and I wanted to ask you, related to the postmenopausal women, did you intentionally exclude any women that were they taking exogenous ah hormonal replacement during menopause or this was kind of accidental? It just happened that they were not taking any and um and um hormonal replacements.
00:25:44
Speaker
ah They were not taking hormone replacement therapy and our study did not include ah perimenopausal period as well. Our inclusion criteria were stop of the menstruation ah in the last one year, at least for one year, and ah lack of irregularities ah in the menstrual cycles. yeah no I yeah understand this, but no women yeah no postmenopausal women were taking ah um you
00:26:15
Speaker
so no not nine one you choose Why did you choose to to exclude them? ah Because ah actually our standpoint ah by analyzing the serum estradiol levels was also a validation for our grouping.
00:26:34
Speaker
ah So ah the thing we would like to investigate is here is that the effect of hormonal changes. Therefore, we we didn't include the woman with hormone replacement therapy.
00:26:49
Speaker
But there are studies out there ah showing that hormone replacement therapy is actually beneficial for periodontal parameters. That's exactly why I bring this up, because it seems to me that it it's becoming, um you know, not that the standard of care, but certainly and large um a large but ah percentage of women in ah menopause do now take hormonal replacements. So it might be worth for us in oral health to ah start looking yeah into the way this management of menopause affects oral health.
Future Research Directions and Current Work
00:27:28
Speaker
I know that it's, you know, i was while I was reading your paper, I'm like, that's a great study.
00:27:32
Speaker
And you guys have so much work to do further, meaning you have good results, But i don't I think that there is so much more ah work to be done, right?
00:27:44
Speaker
Yes, absolutely. Absolutely. It's just the beginning and it's the just one of the potential contributors to the clinical scene we see in periodontium in this group of women. And it's just the beginning. ah There are...
00:28:03
Speaker
other contributors like immune system, which is also new known to be affected by Ostradiol. And also periodontostromal cells are also hormone responsive, ah which may be contributing to this ah situation and so on. As you said, there there are a lot of things that could be asked. And I believe this is a very interesting topic and still have many aspects that need to be uncovered.
00:28:34
Speaker
100%. I'm so happy that we had the chance to discuss about this. um And I really, truly find it a very exciting line of research. So I wonder if there is anything that we didn't cover and you would like to point out, Alp. I know that we took the discussion from you, and but anything that you would like to add?
00:28:56
Speaker
I think they've heard enough of me talking a lot about these different topics, but this was a good opportunity for me to introduce one of the rising stars in our field. And Neel is going to certainly lead this topic. And her career is just starting, obviously, so that's going to be really nice. And I would like to thank you for this opportunity for us to discuss our paper in a larger audience.
00:29:18
Speaker
And one of the things that I really like, and you and I share the same passion, obviously, and that's the reason we're here is to really ah help the and lead the younger investigators to lead our future in terms of periodontology and being curious about the mechanisms.
00:29:37
Speaker
This will be hopefully Niels' career if she as long as she wants to stay in this field or in this topic, but I'm sure there will be much more ah if like inspired a young leaders will be joining our ranks. So I would like to be really, really honored and happy.
00:29:57
Speaker
And thank you for this opportunity of this. Of course, it was my pleasure. And Neil, ah good luck with ah everything and um oh no before i say good luck tell us what's the next thing you're doing now are you work are you looking at staying with the same population and uh examining um other aspects of the population in a cross-sectional fashion are you guys recruiting new cohort what are your plans uh what i'm doing is now is um dissecting different aspects in uh
00:30:32
Speaker
animal models. I'm working with overeaktomized mice right now ah to explore other contributors and before we move back to the clinic ah for some observational and longitudinal studies.
00:30:47
Speaker
That's great. And one thing that you may want to mention, Neil, is about the most recent IADR award that you received. Yeah, for the IADR Periore Research Group, Philips, ah Young Investigator Research Grant. Congratulations, that's great.
00:31:05
Speaker
Thank you, thank you very much. I'm also very excited about that. And ah in in that project, actually, we ah we will keep exploring that ah from the perspective of gingival stromal cells.
00:31:20
Speaker
and um and the impact ah their impact on perio through their oestrogen receptors. I hope next time when I see you, I will have more data to discuss.
00:31:36
Speaker
No, that's great. That's ah amazing. ah Good luck with everything you do. You deserve the the award. It's very well deserved. And I'm really excited that you have this energy and the passion to move your yeah observational findings into more mechanistic studies and understand more about this relationship. So that's that's great.
00:31:58
Speaker
Thank you very much. I really appreciate it.
Conclusion and Call to Action
00:32:01
Speaker
thanks for having us. It's it's a great opportunity. I think it's really important it's really important for our audience and the practicing periodontists as well as the you know residents and educators to have this topic in their mind. And I think we gave them a lot of food for thought today and and and I'm super excited about this.
00:32:25
Speaker
And to our audience, if you really like this episode, share it with a friend and subscribe to the podcast. It's really um important for you to subscribe so you can get the the latest episodes wherever you're listening. So thank you, everybody.
00:32:40
Speaker
Thank you, Alp. Thank you, Neil. And see you soon in Barcelona, hopefully.
00:32:51
Speaker
Thank you.