How Female Biology Shapes Skin Disease Across a Lifetime | Dr. Doral Fredericks, PharmD, MBA - Vice President and Head of Global Medical Affairs and Outcomes Research, Organon

Dr. Doral Fredericks: Sam? Mhm.

Ira Pastor: Um, Welcome to another episode of Progress, Potential and possibilities discussions with fascinating people designing a better tomorrow for all of us. I'm your host, Ira Pastor. Welcome uh, everybody again to another episode of the show. Bringing another really awesome guest for you today. Uh, on the show today we have the honor of being joined by Dr. Doral Fredericks, who is vice president, head of global medical affairs and outcomes research at Oregon, um, global health care company focused on improving women's health, uh, throughout every stage of life. And with over three decades of experience explaining everything from clinical pharmacy, pharmaceutical development, medical affairs, healthcare strategy, Dr. Fredericks has held senior leadership roles across some of the world's leading healthcare organizations, including Organon, Dharma Van Acadia, Bausch and Lomb, Novartis, AstraZeneca and Kaiser Permanente as well. And throughout her career, uh, she has led multiple, uh, medical affair organizations overseeing clinical development programs, wereworld evidence generation, as well as physician education initiatives and outcomes research in uh, multiple therapeutic areas. And uh, today we're going to be, uh, you know, she's focused on driving this really important growing conversation around female dermatology. Um, this field that examines ultimately, uh, how biologic transitions such as pregnancy, postpartum, perimenopause, menopause can really profoundly influence uh, chronic skin conditions, including things like eczema, psoriasis, other inflammatory conditions. And on the episode we're going to explore everything why women's skin health remains such an unrecognized area of medicine, how different hormonal and immune changes throughout a woman's lifespan affect dermatological disease, and ultimately what the future of potentially personalized care, uh, in this area looks like as researchers begin paying much closer attention to this really unique biology. Um, a lot to get into today. Honored to have her. Dr. Doral Fredericks, welcome m to the show.

Dr. Doral Fredericks: Thanks so much for having me. Excited to be here.

Ira Pastor: Yeah, yeah, I'm really excited about this and uh, it's a set of topics that I've not touched on much. So I'm really looking forward to learning a lot from you. Um, start off with a basic definition here. I mean we, to take us into the world of female dermatology. You know, as I mentioned in the bio, you know, this is not just, you know, some skin care products for women. This is a much broader topic in terms of these really dramatic hormonal fluctuations that occur that ultimately change skin throughout the lifetime. Um, tell us a little bit about the space, how you define it and ultimately why. Historically it hasn't been researched as much as it probably should be.

Dr. Doral Fredericks: I really appreciate the fact that you're taking some time to kind of delve into this because it is a really important topic. I mean females make up 50% of the population. And I think one of the most important things to recognize really is that women's skills, skin health, isn't separate from women's health overall. So when we talk about this, it's important to keep that in context. It really is deeply connected. Um, women do experience skin conditions differently and even in probably more of a complex fashion because of a lot of these hormonal changes that happen across the life stages that you talked about, like puberty, pregnancy and menopause. Um, those shifts can really directly affect how skin diseases show up, um, how they flare and how they should be treated. So I think when you understand that biology, it really becomes clear that a one size fits all approach, especially one that historically we've studied in really male physiology, just isn't probably the best approach. Um, and that means that we really need to bring women's hormonal rhythms into the conversation from the very beginning, sort of not as an afterthought. Because when those chronic skin conditions aren't well controlled during the transitions, the impact goes far beyond the skin. I mean if you think about it, and we know that there's evidence to show it can affect mental health, um, things like anxiety and depression, sleep, self esteem and even intimacy in day to day functioning. So these aren't just really soft or secondary effects, they are real, measurable and under recognized in a lot of uh, cases. But importantly, if you think about it and sort of in the overall health context, when issues like depression are part of the picture, they can have some really significant downstream health risks including things like heart attack, stroke and other cardiovascular issues. So this isn't just about improving skin health, it's about taking really a more holistic, proactive approach to women's health overall. And we really can't afford to ignore, I think that connection.

Ira Pastor: Mhm. And along those lines, reading up uh, ahead of this recording on uh, the many hormone responsive components of the skin, I guess we don't, I wasn't thinking as much about the skin as a hormone responsive organ, but sort of just going down the list here of all the things know, uh, these hormones do, I never really knew, uh, ah, before, you know, reading, preparing for your show, uh, that estrogen, you know, stimulates collagen and elastin and HLA production, uh, progesterone, very important, microcirculation and sebaceous gland Activities, Androgens, obviously do a bunch of other stuff as well. But, uh, talk a little bit about this because again, it's something that, you know, obviously there's a very important connection there. We probably don't think about as much as we should. It takes us down that path a bit, if you will, with us.

Dr. Doral Fredericks: Sure, sure. And I mean, happy to go down as far as you want to with regard to how it affects some certain conditions as well. But just holistically, I mean, skin is very receptive to hormones. Um, you know, hormones really are those chemical signals that regulate things like growth, stress and reproduction. Right. That's how we traditionally think about it. Um, hormones act like messengers in the body and the skin has these things, right. Listening spots essentially that are receptors that allow, uh, the skin to react to those hormonal signals. Um, hormones can affect a number of things. Right. How. And you mentioned some of these. How oily or dry your skin is, how easily you get acne or how your skin heals and even how it ages, which goes to the collagen, um, production and things that, that decrease over time. And that's why people often see changes in skin during these different life cycles, during puberty, during pregnancy, menopause, or like in times of stress, because their hormone levels and immune responses are shifting during all those times.

Ira Pastor: And, um, you know, drilling that. And we'll go further into, uh, you know, some of what you're doing there at Oregon on, in terms of, you know, novel approaches. But when we take some of these conditions, and I know I mentioned, you know, in the, the intro psoriasis and eczema, two major skin conditions that you're focused on there obviously major unmet needs on both fronts. But it's just again, so interesting, the sex specific differences, uh, in these conditions, uh, in terms of, you know, pregnancy, you know, uh, for some reason, women with psoriasis seem to improve dramatically during pregnancy, but after birth, then it gets much worse. We see sort of the reverse thing happening in eczema. Ah. Um, and then obviously differences in puberty between boys and girls and all that. Um, take us into some of this because the, um, differences are striking on both fronts. Uh, and again, maybe we don't think as much as we should. And why, for instance, you know, certain hormones act to say, natural immunomodulators or, you know, immunosuppressants or whatever the case may be. But, uh, walk us into psoriasis, into eczema and some of the interesting sort of, uh, themes here that we might not normally Associate again with the connection between sort of the hormonal world and everything that's happening.

Dr. Doral Fredericks: Sure. Great segue. And I think it's one of those things. Let's, let's talk about just sort of what hormonal shifts we see in pregnancy. Pregnancy, postpartum, menopause, and then drill down even deeper. So when we think about skin, I mean, three of the most dramatic and I think often underestimated periods of change are around pregnancy, the postpartum phase and then menopause. Right. And the reason is that, and you touched on this. Skin is incredibly sensitive to hormones, especially estrogen and progesterone. So when those levels shift, the skin responds in very visible and sometimes really unpredictable ways, just like you talked about. So during pregnancy, for example, the body goes through some really rapid changes in hormones, um, but not only that, but also just immune function and circulation. And what's fascinating is that these shifts can indeed have very different effects depending on the individual. So some inflammatory skin conditions actually improve, while others can flare for the first time. At the same time, you have the skin barrier, hydration and sensitivity potentially all changing. Which is why you actually hear about many women noticing their skin behaving differently during pregnancy for the first time. Then you move into this postpartum period, which has even more unpredictability because hormone levels drop really sharply after delivery. And so the immune system is recalibrating and then add the stress and sleep disruption of a newborn. That combination can really trigger things like sudden flare ups of chronic skin conditions, along with things like changes in, um, pigmentation or skin texture that you didn't typically see even before pregnancy. Then in menopause you have a different but equally important set of changes. Um, as estrogen declines over time, the skin will become thinner, drier and less elastic, healing is going to slow, sensitivity increases, and chronic inflammation conditions become really more difficult to manage. Across all of these stages, the common thread is that major hormonal transitions will drive major changes in the skin. Um, historically these life phases really haven't been studied as deeply as they should be. So now we're just really, I think, beginning to hit the surface and understand how profoundly these different life stages are, um, and how they affect not just short term skin changes, but really overall long term skin health. So that's kind of the macro view. Now let's kind of take it down into psoriasis and eczema specifically. So one of the simplest ways to think about this, right, is that hormones shape the immune system and the immune system m will, um, Shape the skin, it's really that direct. So during pregnancy, you see these increases in estrogen and progesterone, and those shifts actually change how the immune system behaves. What's really interesting is that this can have very different effects, as I kind of mentioned, depending on the condition. So some diseases like psoriasis often, uh, will improve during pregnancy, while others, like eczema or atopic dermatitis, can flare or even appear for the first time. So it really highlights how closely I think the skin and immune system are linked with these hormonal changes. Then contrast that with menopause, and it's almost the exact opposite hormonal environment. There's a sustained drop in estrogen and progesterone, and that is associated a lot of times with more severe or harder to control psoriasis and more frequent flares. At the same time, this lower estrogen weakens the skin barrier. And when you combine that with the changes in the aging immune system, um, it can unmask or worsen conditions like eczema, especially in areas like the hands, face, or skin folds. But hormones are just one part of a really complex system, but a really important one that we're still learning a lot about. I think this is also a good time to think about this real world impact that these chronic skin diseases have. These conditions aren't just a clinical diagnosis, right? They affect how people live their lives. So I've had patients talk about the fact that they will avoid getting their hair done because of scalp psoriasis, or they've been turned away from a nail salon because of nail involvement, or others struggle to work because of severe hand or foot eczema. So when we talk about these hormonal shifts, um, immunity changes and skin, it's not just biology. It's about really quality of life, dignity and other daily functioning. And so it's a really important thing that we're talking about.

Ira Pastor: And yeah, I mean, it's again, a fascinating, I'll call it ecology, uh, you know, that you're laying out there. And again, if we, if we go now from, you know, understanding as you just, you know, you know, very ugly laid out there in terms of these major changes that occur throughout life. And then think, you know, okay, so now what do we do in terms of these, uh, unmet needs, clearly, um, things like corticosteroids, which, okay, fine, but those we know over time, uh, become problematic, uh, when we talk about things like pregnancy that limits certain treatment choices. Uh, you pointed out the quality of life issues. Talk a little bit about you know, how you as a pharmaceutical company thinks about these things, of course. And then if you want to, I think it'd be a nice segue into sort of the world of aryl hydrocarbon receptor research. Because this um, and what you're doing here, unlike sort of the steroids and other immunosuppressants, uh, is really taking a much more holistic view of how skin should be treated as opposed to maybe just you know, master regulator shutting off inflammation entirely. No, we have to think right, uh, perimenopause skin, much different than pregnancy skin, much different than menopause skin. Um, think it talk a little bit how that, that makes you think about the types of products you ultimately have to develop for this segment. It's a major segment.

Dr. Doral Fredericks: Yeah, no, that's, that's a really um, excellent question and I think um, is a great point because you know, dermatology as a whole, up until recently, and I'd say, you know, within the last probably five years, give or take, there had really been not a lot of research, especially in topical medications. Um, there's been a lot of research with regard to biologics and fundamentally getting to that sort of um, immune response. But in the last number of years there have been quite a few products that have come on the market um, that are, that are not in steroidals because as you point out the steroids rather great I think for sort of that initial treatment and calming of inflammatory skin conditions. There are these longer term issues with utilizing them and those are well known. So with the aryl hydrocarbon receptors specifically, um, it's been looked at in a variety of diseases. What's great about it for um, skin diseases specifically and in working with that receptor, um, again it's a non steroidal but it hits a number of different places including restoration of the skin barrier. And I think that's one of the things that's, that's most um, dynamic about this class of medication is you're, you're bringing things back into what we call homeostasis, right? So you're bringing the immune responses to a normal level and in addition you're actually seeing restoration um, of that skin barrier. So it's normalizing some skin texture and quality, um, which is a really exciting piece I think of the entire puzzle. Um, I think when we think about the research gap as a whole with regard to um, women's skin health, one of the things that we have to kind of acknowledge is we've historically treated kind of skin diseases as static and for women Specifically, um, it's a really dynamic thing because of all these hormonal changes, right, and they shift across puberty, pregnancy and postpartum, um, um, menopause. And because of that we're missing sort of, I think, the when and the why behind flares, uh, and then the associated treatment response and long term outcomes. So when I think about um, where we need to go with regard to research, especially with female um, dermatology, we need just better, more connected data so linking the skin, the hormone and the immune system over time and combining those with tools like uh, digital biomarkers, things like genomics and proteomics and AI to maybe identify patterns in disease. And really getting to that, what you mentioned earlier, that personalized care is incredibly important and we also need to be able to redesign trials and, and sort of our care models to reflect these differing hormonal stages as meaningful signals, not just sort of this noise that we've seen in clinical studies. So ultimately I think the goal with regard to all of these treatment landscapes and how we're looking at moving, um, clinical research is to move from what I consider reactive treatment care to more predictive care, to be able to anticipate flares, um, to personalize treatment based on where people are in their health journey and then intervening even earlier. Mhm.

Ira Pastor: I like what you said before about you know, this uh, you know, specifically what, what you're working on there with their hydrocarbon research and sort of this principle of restoring broad skin homeostasis and again, you know what, some of the things you're doing, you know, reinforce the skin barrier as well as impact the immune system. I saw there was some, you know, benefit to the microbiome. Then we forget about the importance of the microbiome being on the skin there and all the stuff that lives on us, um, as we have further into this world, as you were just mentioning of personalized medicine, of sort of the next step, uh, in some of this type, uh, of research. I mean what are the technologies that excite you? I mean doing a little research, you know, I've read about the stuff that, that's happening in transcriptomics, uh, and in dermatology. Obviously you mentioned AI. Uh, we've done a lot on the show in terms of wearables, but we don't always think about, okay, you know, it probably be pretty easy to develop wearables to can really monitor how the skin in these particular cases evolves in these unique scenarios. I mean, what's the stuff that you're interested in? What gets you excited? Um, Take us down that path a little bit. Because a lot of things out there that I think would be, you know, perfect as we talk about this future of female dermatology.

Dr. Doral Fredericks: Yeah, yeah. And I think, you know, a lot of these things are really important, not just for female dermatology, but for dermatology, you know, as a whole. Right. Um, but I think right now we often treat sort of skin diseases based on what we see in the moment. And the future really lies to me in when we understand sort of, um, the women's skin in context. Right. Hormonal stages, immune profiles, genetics, even environmental and lifestyle factors, and use that data to predict kind of what is likely to happen next, not just react to it. So from a technology standpoint, I think you're going to see advances in things like AI driven diagnostics, um, digital biomarkers, and even maybe at home monitoring tools that track skin changes over time. So ideally, uh, what we want to get to a point of is being able to anticipate flares before they happen. Because your specific data, whether it's hormonal patterns, um, sleep stress or early skin signals, suggest that you're entering a higher risk window. That's really where the power lies in all of these different technologies that are being developed. Um, and that's where true precision medicine really comes into being. I think kind of going along with that, I hope that we're going to see clinical trials and treatment guidelines that sort of guide not only, um, clinical care but also insurance decision making, uh, evolve to better reflect women's life and the cycles that they have. So incorporating these life stages like pregnancy, postpartum and menopause as essential variables that are, are tracked in these clinical trials, rather than excluding them kind of as we do now, or treating them as confounders. Um, I think equally important with all of this, and this goes a little bit beyond the technology piece, but I'm hopeful that we're going to be able to look at more variables instead of just like, how do we clear skin, but also bringing in more of that quality of life dynamic and assess things like confidence, daily functioning, relationships and long term health risks because of all those things that we know are associated with skin diseases. Right, Those long term sequelae that we talked about. Um, so if I had to sum it up, I guess the future, I think of, uh, female dermatology is about really seeing the whole person, not just the skin, and using better data, better science and better integration across disciplines even to deliver care that's truly tailored to women across their entire life. Course, and meeting them at the place that they are, it's pretty aspirational, but I really do think it is attainable over time as well.

Ira Pastor: Absolutely. And, you know, obviously you're. You're making a lot of progress, you know, in the eczema space, in the psoriasis space, with some of the current, current, uh, launches. Um, what else is coming up that we should know about while we have you today, either per the pipeline in terms of immunodermatology, I'll call it, that you're involved in, and then, uh, anything else public, uh, facing for Uterall, uh, conferences, talks, other initiatives, as you get the message out there about the future of female dermatology while we have anything, please.

Dr. Doral Fredericks: Yeah, I think, you know, the biggest opportunity that we have as Organon is looking for ways to bring our mission, which is a healthier every day for every girl and woman to life. So that really means that we're constantly looking for opportunities to work not only with healthcare providers and the healthcare community, but I think also groups like patient advocacy organizations. So we do a lot of work with, um, groups like the National Eczema association, the National Psoriasis foundation in the US on programming and resources that directly input patients. We are also looking at ways to incorporate the patient voice into our clinical studies. And that's another way that we partner with these organizations to really, um, have dialogues and with patients that are affected by these chronic conditions and ensure that we're looking at endpoints, um, and looking at quality of life measures and things that are really impactful for them. Specifically. Um, we also work really closely with the Women's Dermatologic Society, which is focused on female healthcare providers in the dermatology field and even more broadly than dermatology. You know, we're very engaged with things like the Gates foundation, uh, for women's health overall. So we're just constantly looking for these opportunities to partner and really make an impact on women's health. Besides, just in the clinical trial perspective, but really making more of an impact on just awareness and identifying these opportunities. I think it's a really important thing for, um, for all patients worldwide. And something that, um, really we haven't given enough, I think, respect and just garnered enough groundswell to do in the past as an industry and something that I'm hoping Organon can continue to latch onto and just do more and more work.

Ira Pastor: Well, you're clearly, uh, getting it done. I mean, it's, um, as you started off by saying, we're talking about half the population of of the world here, uh, that, you know, in many ways has been overlooked in these very important unmet medical conditions integrally tied to these unique phases of life. Uh, and, uh, yeah, it's extremely impressive work. I love the fact that you're not only getting the message out there, but obviously filling up the pipeline with these novel therapeutic approaches as well. But again, uh, very impressive, um, again, for everybody out there, um, that is going to be listening to this episode, uh, across the, uh, various podcast networks or who will be watching on the YouTube channel. Again, you've been spending time with Dr. Dural Fredericks, Vice President, Head of Global Medical affairs and Outcomes Research at Organon, doing really amazing work to develop these novel therapeutics to improve women's health throughout every stage of life. Uh, Doral, again, I want to thank you for taking the time out of your schedule today to come talk to us for a little while to educate us on a really important range of topics. Uh, thank you for everything you do there at Oregon, and as we'd like to see here on our show, thanks for helping to create a better tomorrow through the development of these new technologies and products. Uh, it's a great story, and I look forward to helping you share it and, uh, continue to follow the work you do.

Dr. Doral Fredericks: Thank you.

Ira Pastor: Really great having you.

Dr. Doral Fredericks: Great being here.