#17: Electrifying Relief: Dr Emile Radyte’s Brain Stimulation Approach for Menstrual Pain and Mood

A Neuroscientific Approach to Menstrual Wellness with Dr Emile Radyte: Exploring Brain-Based Pain and Mood Therapies

In this episode, we welcome Dr Emile Radyte, a Harvard and Oxford-trained neuroscientist specialising in how the brain influences menstrual mood and pain

Dr Radyte discusses her extensive background, including her leadership at Harvard’s emergency medical service and the founding of Lithuania’s largest neuroscience NGO. She is the co-founder of a neuroscience company focused on a brain-first approach to menstrual wellness. The conversation dives deep into the neuroscience behind menstrual pain and mood, explaining how brain circuits, rather than just hormones, regulate these experiences

Dr Radyte elaborates on the innovative non-invasive brain stimulation techniques her team is developing to provide pain relief and mood stabilisation for women with conditions such as PMS, PMDD and endometriosis. She also shares insights on the interplay between hormones, neuroplasticity and brain circuits, as well as ongoing clinical trials and the personalisation of therapeutic protocols for different conditions

Throughout the episode, she highlights the crucial role of self-tracking and personal responsibility in women’s health optimisation

Timestamp

00:00 Introduction and guest welcome
01:05 Understanding the brain-first approach to menstrual health
02:57 Brain circuits and emotional regulation
06:54 Pain perception and sensitivity
09:19 PMS vs PMDD: clinical definitions and differences
12:54 Brain stimulation: a new approach to menstrual health
29:14 Devices and technology for menstrual wellness
35:50 Understanding women’s symptoms and tracking
37:32 Common user mistakes and how to avoid them
41:06 Clinical trials and research initiatives
50:33 User experience with the devices
01:00:43 Curveball questions and personal insights

Resources Mentioned in This Episode

1. Samphire Neurotechnology

• Samphire is a neurotechnology company focused on women’s brain health, particularly hormonal-cycle related symptoms such as:
  • PMS
  • PMDD
  • Menstrual migraines
  • Brain fog
  • Mood and cognitive disruption linked to hormonal changes
• The technology discussed is non-invasive neuromodulation, designed as a drug-free alternative for managing symptoms.

2. Neuroscience & Hormonal Health

• Discussion around how hormonal fluctuations impact the brain, not just reproductive organs.
• Emphasis on the lack of research funding and innovation in women’s neurological health.
• The gap between male-centric medical research models and women’s lived neurological experiences.
  
  

3. Clinical & Regulatory Context

• Samphire’s work within regulated medical frameworks.
• Importance of clinical validation, safety, and evidence-based design for women’s health technology.
• Barriers women face accessing care for cycle-linked neurological symptoms.

4. Lived Experience & Advocacy

• Emile shares the personal motivation behind building Samphire.
• Reframing “normal” suffering around periods and hormones.
• Advocating for women to expect better solutions, not just coping strategies.
  
  
  

Social Media Links

Samphire Website: https://url-shortener.me/4QQW 
LinkedIn:https://www.linkedin.com/in/eradyte/

Instagram:https://www.instagram.com/radytee/?hl=en

Insta/TikTok: @BiohackingEve
Website: www.BiohackingEve.com

Transcript

Dr Emile Radyte 0:00

one of the key levels and key ways that the brain interprets it, is in an area of the brain called the posterior insula. Also very deep in the brain and pretty difficult to reach. But essentially that part of the brain is responsible for setting your pain sensitivity threshold. So one person's pain sensitivity is higher than another's, and I'm sure everybody has experienced it. It can be seen with heat sensitivity, cold sensitivity, and pain sensitivity, and another areas like that. But curiously, for women across different hormonal profiles, so across the menstrual cycle, but also around menopause, around pregnancy, our pain sensitivity changes and it changes in that specific area in the posterior insula. And one of the patterns we see is that right before your period, you're hit with a double whammy. On the one hand, you're having your uterine lining about to shed, so there's a physical tearing process about to happen. But on the other hand, your pain sensitivity actually increases. You're more sensitive to pain during your period than during other periods of time, which feels a bit counterintuitive. And essentially it's just supposed to help your body prepare for it. And for example, one of the ways in which brain stimulation deals with it. Is essentially not allowing that pain sensitivity threshold to shift. And so allowing you to essentially still undergo that same physical process but not be as sensitive to which, which for most. people means that they don't even feel pain effects altogether. And then we restore that balance for emotional control and for pain sensitivity, as I mentioned, as the pain sensitivity is trying to increase. That's again, an electrical signal and we just don't let it increase. So we keep your pain sensitivity to wherever it is and don't let it get hyper sensitized ahead of your period.

1:34

Welcome back to Biohacking Eve, health Optimization for Women with Judith Miller, where we shine a light on everything that will help you reach your best self. As a woman, as unique and individual as then you can be live long and prosper my friend.

Judith Mueller 1:55

Hello and welcome back everyone. Today we have Dr. Emily Radyte on the show. Hi Emily.

Dr Emile Radyte 2:01

Hi, great to be here.

Judith Mueller 2:03

So Emily is a Harvard and Oxford trained neuroscientist focus on how the brain shapes menstrual mood and pain. She's previously led Harvard's emergency medical services with the team of we're gonna talk devices a lot, but we'll stick with the services for now. So you've had a team of 90 people under you, and you've also co-founded Lithuania's largest neuroscience, NGO, the Integrative of Neuroscience Association with a 40% team. You've also been named on the Forbes 30 and the 30 list on your current co-founder Aner of PHI Neuroscience, which is applying a brain first approach to menstrual wellness. So today we're gonna talk about how period, mood and pain are gathered by brain circuits, not just hormones, and how time targeted non-invasive brain simulation can actually nudge those circuits for relief and steadier mood. Fantastic. Let's start with what do you mean by brain first approach to menstrual health and how is that different from the usual story of it's just your hormones.

Dr Emile Radyte 3:06

I think if we trace back, most women know about their menstrual cycles from their lived experiences. And in fact, for a very long time, people thought of their menstrual cycles as just their period. So the day they get a bleed, they think that's their period. And over the last, I'd say 20, 30 years, there has been a little bit more education, public awareness, as well as obviously. A lot of advocacy and more media attention to this that has moved the needle to educating women of the fact that their hormones. change throughout the menstrual cycle. So the day that is relevant to your menstruation isn't actually only the day that you bleed, but also

Judith Mueller 3:38

Also every

Dr Emile Radyte 3:39

specific pattern of hormonal function throughout it. And I think now there's this association of these patterns that are relevant throughout your lifetime and that they can change throughout your lifetime in different phases of your life. But still with a hormone first approach. So now we're talking about that hormone difference, but only in the last, I would say, three to four years, which is a little bit shorter than I have been in the industry. People have finally realized that

Judith Mueller 4:01

realized that.

Dr Emile Radyte 4:02

center for every single hormone is in the brain. And so unless you're talking about the brain in anything hormone related, you are missing part of the story and part of the loop. And so even though, step one is understanding that your day one of the cycle is your bleeding, your period, and the menstrual cycle is all of that. pattern, as well as how it might change through perimenopause, postpartum, or other adjustments to your cycle, like hormonal contraception or say egg freezing or IVF treatments or whatever it may be. It is always controlled by brain based circuits. And so we wanna take a brain first approach to educating women about what those patterns are and how to be in charge of them as well.

Judith Mueller 4:39

The brain is probably the most complex organ that we've got. There's various different areas, and I believe various different areas actually involved in both pain and mood. Can you tell us which circuits we're actually targeting, what they're responsible for, et cetera.

Dr Emile Radyte 4:53

Yeah. High level when we're talking about targeting pain and mood circuits, they're very distributed in the brain. So when it comes to mood circuits, the most important relationship to understand is between top-down regulation, which comes from the prefrontal cortex. So the prefrontal cortex roughly is this area that you can cover on your head. So pretty much above your eyebrows if you project inside your head up to about the midline. If you draw drew a line between both of your ears, that's where the prefrontal cortex sits is a part of your brain responsible for emotional regulation, top-down control, executive function, decision making. And a lot of people may have heard of it in another name called the frontal lobe. It's one in the same thing. And most

Judith Mueller 5:31

And most.

Dr Emile Radyte 5:31

controls the limbic system, which is a part much deeper in the brain that we actually share with a lot of other animals that is responsible for emotional control. And in our day-to-day life, the way that the brain functions is actually in the balance between the two. So essentially, your limbic system, which contains areas that you might have heard of, such as amygdala, responsible for fear response hippocampus responsible for memory and other parts like that. They're responsible for you responding to things very quickly and reacting to them very quickly and knowing how you feel about them. But then your prefrontal cortex helps you interpret those signals. So as an example, if you're, let's say you're afraid of public speaking, it's because every time you stand in front of a lot of people, your amygdala goes scary thing, lots of people staring at me, I should run. And then your prefrontal cortex tells you that these humans aren't about to eat you, and it's actually a safe space, and then it's supposed to calm you down. And it's actually that regulation between the two. And when it comes to emotional regulation, and actually a lot of my doctoral work was in the field of depression, so major depressive disorder. One of the things that happens is a dysregulation in the balance between two hemispheres at the prefrontal cortex level. So specifically the left hemisphere in the prefrontal cortex becomes underactive or what we call hypoactive. And then the right hemisphere becomes hyperactive as a result. While normally the right and left hemisphere of the prefrontal cortex are supposed to communicate evenly in order to control that limbic system and that immediate emotional response, they become out of balance. And so they can no longer regulate those emotions top down, and so they can't help you interpret whatever feelings you're feeling. In the case of depression, it means you're feeling sad, but then that sadness is unexplained, and so that gets exacerbated up until the point where you do develop symptoms of depression. It's very similar in generalized anxiety disorder, where you get a little bit of fear, but then your prefrontal cortex doesn't help you interpret that fear and then suddenly that fear. Built out into this anxiety that isn't linked to anything specific. You're just anxious And fearful. And one of the things that we see across menstrual cycles is that in that week, leading up to your period in response to the hormone progesterone, which lifts up in the luteal phase, so following ovulation, usually in the days 14 to 28 of an average menstrual cycle, essentially we see that same pattern of dysregulation in the prefrontal cortex. And as a result, women struggle, especially during that time, to have top-down regulation of their emotions. And so even though when you hear of PMS or premenstrual syndrome, you think of so many different symptoms, say low mood anxiety, but also mood swings or anger, irritability issues. A neuroscientist listening to all that hears that there's some emotional regulation. Issue. And that comes down to the fact that prefrontal cortex isn't communicating effectively enough to control that limbic system response. So a lot of the mood disorders exist somewhere in that range. And obviously people might experience different overlaps of those functions, but that's the high level of how it works. And it also overlaps with a lot of other conditions, especially in women, such as things like A DHD and autism and a wide range of neurodiversity that is only now being discovered in women altogether. so for example, in a lot of our technological work, those are the specific patterns we work with and happy to dive into that deeper. And then when it comes to pain to touch on a different mechanism, in a different part of the brain is that a lot of people feel like pain is localized. So for example, I hit my leg hurts, I hit my arm hurts. Those are clear levels of pain. But increasing numbers of society live with what we call chronic pain or distilled pain where you are in pain, but you can't necessarily say where exactly it is. At a neuroscientific or neurological level, we consider a lot of the pain to be based on pain perception in the brain. It doesn't mean it doesn't exist locally in that specific muscle or region of the body where it's coming from, but the signal is processed and the severity of pain is interpreted in the brain. The brain is the tool that interprets the severity of the pain. And one of the key levels and key ways that the brain interprets it, is in an area of the brain called the posterior insula. Also very deep in the brain and pretty difficult to reach. But essentially that part of the brain is responsible for setting your pain sensitivity threshold. So one person's pain sensitivity is higher than another's, and I'm sure everybody has experienced it. It can be seen with heat sensitivity, cold sensitivity, and pain sensitivity, and another areas like that. But curiously, for women across different hormonal profiles, so across the menstrual cycle, but also around menopause, around pregnancy, our pain sensitivity changes and it changes in that specific area in the posterior insula. And one of the patterns we see is that right before your period, you're hit with a double whammy. On the one hand, you're having your uterine lining about to shed, so there's a physical tearing process about to happen. But on the other hand, your pain sensitivity actually increases. You're more sensitive to pain during your period than during other periods of time, which feels a bit counterintuitive. And essentially it's just supposed to help your body prepare for it. And for example, one of the ways in which brain stimulation deals with it. Is essentially not allowing that pain sensitivity threshold to shift. And so allowing you to essentially still undergo that same physical process but not be as sensitive to which, which for most. people means that they don't even feel pain effects altogether. And that's also explains why some women, all women menstruate the same way in terms of getting the endometrial lining shedding, but some may be experiencing excruciating pain and others not at all. Even though, again, biologically the process is the same, the brain perception is different. So we can engage those networks indirectly as well.

Judith Mueller 10:49

It's an interesting point'cause you mentioned your work was in depression. What is the difference and also what are the clinical definitions of PMS versus PMDD?

Dr Emile Radyte 10:58

Great question. PMS stands for premenstrual syndrome and PMDD? stands for premenstrual dysphoric disorder. PMDD is an official condition included in the ICD 11, so the latest iteration of the clinician's kind of diagnostic criteria as well. And is this considered a form of depressive disorder? So for those in the audience who might not be aware, essentially it's a condition that impacts women about two weeks leading up to their period. On average though, there's slightly different profiles as well, and it's characteristic with symptoms of very similar to major depressive disorder, low mood, anxiety, irritability. Notably, there is a very high risk of suicidal ideation, in particular in this population as well. And then all of those symptoms characteristically resolve with the beginning of the period or just a day after. So it's this thing that lasts for two weeks, then seems to go away, and then re returns again. Which is obviously not the case with depression. That is ongoing. And then the other difference also from depression is that it does have a little bit more traits around impulsivity. A lot of people with depression Do not have impulsivity, but a lot of women experiencing PMDD might have these additional symptoms that we don't see in the classic. MDD or major depressive disorder type. And so the main difference in PMS on the other hand is any type of symptom that you could experience in that luteal phase. Usually PMS is shorter, so about a week now, the two weeks before your period, and it can have those same ranges of symptoms as PMDD, but it's usually considered on a less severe level, less consistently may be appearing and often has slightly more physical symptoms looped into it as well. Symptoms like bloating acne as well. Whereas PMDD is specifically a mood related disorder that can be diagnosed and most importantly, PMDD because it's now being recognized, though still a lot of clinicians don't know about it, can be treated with some options. Usually they're just adapted options from major depressive disorder treatments. But PMS generally doesn't really have medical grade solutions because historically it wasn't considered very serious. But again, for many women, it does take about a quarter of their lives.

Judith Mueller 12:56

Do we have statistics of how many women or what percentage of women either have PMS and or PMDD.

Dr Emile Radyte 13:03

We do, and they're incredibly unsatisfying, as is, as are many things in the space. So the estimate is that about 30 to 90% of women experience PMS symptoms some form of PMS symptom. The way I like to think about it is that about an. Nine in 10 women will have experienced at least one PMS symptom reliably throughout their lives. Many of them might not connect it necessarily to their periods, but again, a very common PMS symptom is brain fog. And I think most women would recognize, at least retrospectively, that's what it was linked to. But as I was mentioning the history of tracking menstrual cycles and getting them acknowledged is still very new. But that's that wide range. PMDD is seen as less common in society. It's estimated at three to 8% more recent estimates put it up to around 10 to 12%, given the fact that it has only been included in ICD 11 very recently. So it actually couldn't have been diagnosed. So it was more diagnosed in more rogue way by more progressive psychiatrists in particular. But

Judith Mueller 13:57

So let's have, unsurprisingly actually let's have a look at what it is that you're developing. So traditionally, people would've used painkillers, so you would've used heat therapy that we've used, all sorts of things. What is it that you're working on? We've talked a lot, the brain a lot. Tell us more about brain simulation, how that works.

Dr Emile Radyte 14:16

Sure. So brain stimulation to give people a little bit of a run through of how that developed. So the brain communicates in two main ways, the chemical and the electrical way people know about the chemical way a lot. So those are things like neurotransmitters that everybody now has popularized. Things like dopamine, serotonin, they're the chemical way that the brain communicates, but equally, the brain can only work if it's wired electrically as well. So those are things that, you know, as neuronal networks, neuronal patterns and things like that. So for many years, when it came to treatment of brain disorders from, depression and anxiety to now, let's say PMDD, we only focus on the chemical system. So let's say calling them serotonin deplete disorders and then adding serotonin through SSRIs. Or dopamine or whatever neurotransmitter might be. But what the problem with all of those treatments was, is that receptors for neurotransmitters are distributed across the brain. You pretty much can't find a lot of the bits of the brain that wouldn't have a dopamine receptor or serotonin receptor, which means when you take a medication, which traditionally are taking through the mouth orally and it gets broken down, it floods the entire brain. So you actually very rarely can have specialized effects. And in fact, if you look at the side effects of most psychiatric medications, which obviously are trying to target the brain. All of their side effects actually impact the rest of your body. And those are the reasons why people discontinue the treatments. It's because they do this kind of flood all approach and hope for the best. And so over the last 30, 40 years, brain stimulation has really come up as a way to be more targeted when it comes to the brain and it focuses on the electrical rather than the chemical system. So it's a more recent way of looking at it, but really the system is equally as old school, as the neurotransmitter system as well. And its principle is essentially to use electrical currents or magnetic fields in order to push brain activity into a particular direction. So the way that it's being pushed is essentially adding a small electrical pulse or a magnetic field pulse as well, and then encouraging the, signals to go in a particular direction that we intended to. Most importantly, it's much more targeted because you literally put it on top of your head and there's two types of brain stimulation. A lot of people usually think of the invasive types. So when you have an implant, for those in the audience who are familiar, had unfortunate experiences of being exposed to Parkinson's disease deep brain stimulation is one of the most common treatments for it. And that's when you get a little implant that uses exactly that brain stimulation deep in the brain in order to reduce tremors in people living with Parkinson's. But also now we have invasive treatments for other conditions as well. But that requires brain surgery. You're literally implanting a brain stimulator inside your brain for most conditions. That could be resolved or could be reversible as well. We're trying to go more the non-invasive approach, and that's the field that I'm part of and have been working in for a while and. That's about 30 to 40 years old. And in non-invasive brain stimulation, you have either electrical or magnetic stimulation. Magnetic stimulation by default, can only be done in the clinic for now. So essentially, you go in and a strong magnetic field is applied over a small period of the area of the brain. And for example, the most common treatment with that is called TMS or transcranial magnetic stimulation. It's an approved treatment for depression. It's actually reimbursed after multiple areas, after you've tried multiple antidepressants because of how expensive it is. And then on the other hand, you have electrical stimulation, which is safe to use at home, such as the one that we've developed at samphire. And that can be targeted, safe to use at home, uses weaker pulses than magnetic stimulation, but can be used more frequently because it's in an at-home setting. And it essentially encourages the brain activity to go in a particular direction. And frankly, it does what it says on the tin. So when we're discussing the mood patterns in particular. We know that there's that unevenness in the prefrontal cortex causing the left hemisphere to be underactive and the right hemisphere to be hyperactive. We literally do that. We add electricity to the one that's underactive, to give it a little boost to reconnect with the one that's hyperactive, and then we inhibit the one that's hyperactive in a very smooth way. And we do rely a lot on the brain's neuroplasticity itself to maintain those effects. And then we restore that balance for emotional control and for pain sensitivity, as I mentioned, as the pain sensitivity is trying to increase. That's again, an electrical signal and we just don't let it increase. So we keep your pain sensitivity to wherever it is and don't let it get hyper sensitized ahead of your period. And so that's how we control that in a more top down way in a safe to use way at home.

Judith Mueller 18:28

So why does. Recalibrating the activity levels of the different hemispheres of the prefrontal cortex. So why are they out of balance in the first place and why does that imbalance actually cause the mood issues in this case?

Dr Emile Radyte 18:45

Yeah, why they're out of balance is not very well understood. We do know that generally that out of balance happens for most people, but to different degrees. We do know that if you look at some peoples, and you can measure that with EEGs which are superficial kind of electrodes on the brain, and you can see what's called alpha waves being unbalanced as specifically it's alpha asymmetry is what this concept is called. We don't know why it's different and why it goes awry. Do know that it responds to progesterone sensitively. And if you look at a graph of how hormones are distributed across the menstrual cycle, the short of it is that essentially as your period starts, so you're bleeding, your estrogen is coming up, but all the other hormones are seeing relatively low. Your estrogen peaks at your ovulation and then goes slightly down and has just a very small peak. Again, midway through the lute phase, progesterone is low throughout your follicular phase. So the first half of your menstrual cycle and then peaks in a hatch shape midway through your luteal phase. So that's when it's come up and then it goes down again if the egg wasn't fertilized and then keeps going up if the egg was fertilized in your pregnant. And so essentially progesterone becomes only visible in the luteal phase, and as progesterone comes comes up into the bloodstream, that's when we see that asymmetry coming up as well. But again, as I mentioned, different people's, of that asymmetry are different, even though the hormonal change is relatively similar. And we don't know exactly why that's the case? And the reason that a asymmetry kind of cor correction works is because we put you back into that follicular phase where you were before. Avoiding that a asymmetric phase while not interfering with progesterone. And so allowing you to menstruate freely.

Judith Mueller 20:20

And for the pain sensitivity, what is it about the electrical stimulation that keeps the, I guess that keeps the pain center engaged, or how does that work exactly?

Dr Emile Radyte 20:32

Yeah, great question. Way that pain is usually communicated is let's say you have a source of pain. So let's say you've hit your leg. Then at the area locally, there are some cells being released, like communication patterns in order to tell the brain that, look, your leg is hurting and therefore you should do something about it. Usually it's communicated with molecules called prostaglandins. And so essentially the way to think about them is that the more pain there is, the more of those prostaglandins are released. So essentially the more severe the damage, the more of those molecules are released. And that makes sense evolutionarily, because you wanna know how bad the damage is, and it should hurt proportionately so that you could respond proportionally, and then those little kind of molecules are supposed to travel from your. Straight up through your bloodstream, up to your brain, and then they're received by the brain. And then the brain pretty much does the counting mechanism. Okay, in one minute, how many of those molecules am I getting? And based on that, it determines in how much pain you are. And then obviously sets it based on your pain sensitivity threshold. So just to do a little click into the pain sensitivity threshold. So imagine a line, and that's how sensitive you are to pain. Everything that's lower than the line, you will just not consider pain. So you will still feel it, but try pushing on your hand. You will just feel pressure. You won't call it pain. And then at some level, as you push it, it starts hurting and you say, ouch, that's your pain sensitivity threshold. So it's not that you are insensitive to things, it's just you wouldn't categorize them as painful experiences. And that's what we're trying to alter. Essentially so that determination and that threshold setting is continuously getting updated in that area that I mentioned earlier called the posterior insula deep in the brain. And that's connected to all other areas of the brain because essentially. What one, it needs to know how much pain is experiencing. So it needs to work with other parts of the brain to know where the pain is, how many of those prostaglandins there is, what is happening. And that needs to also respond proportionally. Do I remove my leg? What do I do about it? It, it needs to be coordinated with it. So in brain stimulations case in particular, we stimulate what's called the motor cortex, which has been shown to have indirect links into the posterior insula because that's very deep. So we can't do that non-invasively. So we need to stimulate something, a structure that is more superficial and accessible, non-invasively. So we stimulate the motor cortex, and if you do it at the right time, at the right place, essentially we can engage the posterior insula. And the reason we can engage it is it's because. During that time leading up to your period, or in some women with, let's say chronic pelvic pain and endometriosis, posterior insula is actively looking for inputs. It's looking for change because it's undergoing this hormonal transition. And so we engage it at the right time and the right place and tell it to calm down and relax and bring the threshold down again. So inhibiting it back again. And so when those signals, let's say in the case of periods come in being like, okay, your uterine lining is shedding and it's counting all of those prostaglandins, we just make it perceive as pressure or maybe, some other physiological aspect. You just wouldn't call it painful. And so oftentimes when people have their first time with brain stimulation, they're a little bit surprised because one, you are very conscious. It's not like an antidepressant or an anxiolytic that takes over your brain function. You're still the one in charge. We're just changing those little perception bits, but they're like, it's not like the period wasn't there, the period was happening. I was feeling it just wasn't painful. Yeah. And I think it's difficult to describe until you've felt it as well.

Judith Mueller 23:44

To moving the individual pain threshold, et cetera.

Dr Emile Radyte 23:47

Exactly.

Judith Mueller 23:48

that's measured on what's called the VAS scale, which is zero to 10. And that's something very subjective, isn't it? So how do you deal with that in the clinical setting?

Dr Emile Radyte 23:57

Great question. So one learning for me, diving deeper into the pain space is that every single painkiller that's on the market, including opiate, devices are actually approved on the VAS. So the visual analog scale, which is essentially smiley faces from very sad, angry face to very happy face visual. And then there's NRS, the numerical rating scale, which is exactly what you said, the zero to 10 of like on a scale from one to 10, how much pain are you in And whether that can increase. And I was shocked to find out that's. Still the golden standard of the way for any pain intervention to be approved. So any pain relief is approved on that one to 10 scale. In our clinical trials, we obviously left to go a step further. So we do those classic scales just so we can be comparable to other types of pain relief. But we also do the PPT or the pain pressure threshold test, which does exactly what it says on the, so essentially what you do is you have this device that you push against different areas of your body. Most commonly it's actually the stomach. And so essentially you push it and then the person needs to click at the point where it changes from pressure to pain. So exactly that bit of you're always feeling it, but when would you start categorizing it as pain? So what you'll notice about all of those measures is that. Even though the pain pressure threshold pretends to be a little bit more objective, it's still about the individual definition of where that pain sits. And I think that's the underlying problem with any type of pain research is that it is subjective. As someone that has spent most of my career looking at people's brains and, validating people that depression is a real condition, it does exist in your body. Just because it's invisible, like a lot of invisible disabilities, doesn't mean it's not there. I think that it's actually the most powerful thing that we can do about pain is to recognize that it's fully subjective and yet it's fully valid. All the same.

Judith Mueller 25:36

And it's interesting because that the one that you just mentioned is actually just measuring the threshold that's the same pain or no pain at what level. But it doesn't actually say, okay, this is painful, versus this is really painful. So interesting issues on the measurement.

Dr Emile Radyte 25:49

as well, but there will always be subjective as again, because, depending on your threshold, something that is very painful for someone will only be very painful for someone else.

Judith Mueller 25:57

this is not something you could measure via electrical signals in the brain at all.

Dr Emile Radyte 26:01

So you can measure changes in essentially like a lot of it is proxied by what are called beta waves in specific parts of the brain, but they're usually more like binary measures. So are you in pain or not? Because essentially the brain has patterns of working under different conditions. And the best example for that would be stress. Like you have your brain at ease and your brain under stress. Similarly, the brain kind of has the brain version not in pain and the version in pain. And when you're in pain, you would think that, oh, there's this region that measures actively how much pain you are, but actually the whole brain needs to reset because is it pain that is useful? Is it useless? Should I run? It's also the fight or flight response. Like it gets so muddy that measuring any individual activity very clearly in the brain gets very confusing. We distill, at least in our current state of affairs with signal processing. I'm sure we'll get there.

Judith Mueller 26:51

I'd like to come back to the hormone basis, brain circuit aspect. Basic. So we're saying this is not hormone replacement and we're actually saying this is short lift. We're not. We're wiring the brain. We are, but we are not. Tell us more about that.

Dr Emile Radyte 27:04

Yeah, so the concept of neuroplasticity is essentially the brain's ability to change and the brain changes most actively, obviously, in the developing child. And a lot of people will have heard of oh, quote, the brain stops developing at the age of 25. That is not true. The brain continues changing throughout life, and there are varying major events that. can reroute it. The most commonly known are things like trauma, like traumatic episodes can really reroute the brain in an unfortunate way, but also for women, things like undergoing pregnancy and motherhood. Massively rewires the brain as well going through menopause again. And like these big hormonal shifts will rewire it again. So neuroplasticity is an ongoing process by which our brain changes and learning a new language will trigger neuroplasticity as well. And essentially the way that neuroplasticity can work is on different levels. So essentially, neuroplasticity needs to always be maintained in order to stick to it. So it can also degrade whenever it's no longer useful. And so with brain stimulation in general, the type of brain stimulation we do, which is non-invasive electrical brain stimulation. We do what's called medium term stimulation. So we help you develop neuroplasticity to adjust to this hormonal change, therefore not experiencing pain and improving your mood over cycles for some period of time. But then as you stop using it, usually within a month to two months, your symptoms will come back and usually will go back to baseline. There are some women where, especially with lower symptoms, where actually, you know, three to six months of using our devices actually allow them to build up those networks themselves so that when their period comes again, they no longer have that hormonal sensitivity and their brain has learned how to adjust to it without support because again, the support is relatively light. But for most people who have those like asymmetric changes or the pain threshold changes be very massive, they do usually need a little bit of an extra boost in an ongoing way. But yeah, if you were to do it very intensively over long periods of time, that effect would be proportional. It would just never stick. And the way to think about it. In comparison to medication or drugs, is that drugs create a dependency because they add something external to your brain, so they add like molecules that your brain depends on. And whenever the brain sees molecules say extra serotonin, it decide that it doesn't need to produce as much, so it becomes reliant on it. Whereas with brain stimulation, you're actually not adding anything into the system, you're just adding a little bit of a jolt for it to do its own job. And so you're like a, like one of those annoying teachers that kind of pushes you to do your best, but doesn't tell you what the answer is. And that's why it mechanistically can't be addictive and can't be long term as well. And obviously it comes with pros and cons for something like periods and women's health. We think it's a huge pro because nothing is permanent in the life of a woman. But obviously when it comes to things like Parkinson's, it makes sense that those stimulators need to be implanted because obviously it's a condition that needs continuous and ongoing supported monitoring, which non-invasively one would be very challenging to do, but potentially possible, but then would require very high levels of support anyway.

Judith Mueller 29:48

And that would also be a condition that actually deteriorates, which ideally, as you said, we do have changes, but it's not necessarily deterioration.

Dr Emile Radyte 29:55

Exactly.

Judith Mueller 29:56

tell us more about what you're building. So you're building two different devices.

Dr Emile Radyte 30:00

Yeah, exactly. So at the moment we have two devices. and a system that controls them available on the market. So our main device is called Nettle. It's a medical grade device available across Europe and the uk. It is approved for the treatment of pain and mood symptoms associated with periods, everything we're talking about. The most common use case for it is actually people living with severe PMS. So mood symptoms associated with their periods. PMDD And endometriosis are very common use user groups that we see. And it's mostly because their symptoms obviously interfere with their life the most. But we cover all ranges of symptoms as well. And the way you use the device is controlled by an app that's our samphire app. And it personalizes based on your age, your experience, your hormonal profile. So whether you are on contraceptives or were on contraceptives, whatever your goals are, we can adjust accordingly and give you a protocol for most people. Usually device use will mean five to 10 days leading up to your period, you'll put on the device for 20 minutes a day. During those 20 minutes, you just have this beautiful headband on your head and you can do whatever you want. We do offer targeted meditation, breath work, as well as education around these issues so that you could understand what exactly is happening. But you can also write your emails, do yoga, whatever floats your boat. And then our other device, Lutia, uses the same technology and is available outside of Europe and the uk. It is a wellness focused device. The kind of focuses on helping you balance out that prefrontal cortex activity at any point of time related to that hormonal change that would trigger that asymmetry. So in there we see a lot more kind of use cases around these hormonal shifts that get triggered a little bit unexpectedly. So perimenopause is very common where kind of your cycles, start shifting a little bit and you start experiencing things like brain fog and those same mood symptoms, but at unusual times. Also very commonly around people who are trying to conceive. So oftentimes either taking extra hormones which might make them extra sensitive to those mood changes or just stopping to use hormonal contraception that was hiding a lot of those symptoms. And so trying to manage that in a hormone free and drug free way. And then yeah, obviously egg freezing would be another case study as well. And both of those devices are controlled through the samphire ecosystem. And I think most importantly is we have this patent algorithm by which we adapt it to your cycle, not only to recommend the best protocol for you. But also as you improve, we actually look at your symptom tracking and are able to change the way your protocols and pattern changes. Because one of the things we're very cognizant of is that your cycle will change throughout your life. And even though we're talking about the menstrual cycle, women's always live with so many cycles. We always have the circadian cycle and at least the menstrual cycle. Then with perimenopause, we probably have all three. If you've recently had kids in the last two years, you probably also have the postpartum cycle. There's a lot going on all the time, and everyone's individual journey is different. So we're trying to adapt to that. And you can actually use the app even without using the devices to just understand what your pattern is, understand whether the symptoms you're experiencing are cyclical, and then whether or not you need support. Because I think front and foremost for me as a, educator and a neuroscientist in the space is bringing that brain first approach. The moment women understand that everything is controlled in the brain, I think so many things click and then your approaches and the way you manage it is up to you. But I do think that empowerment is really important to just know. in charge here. And that is, unfortunately the brain, even if the culprit is the hormone,

Judith Mueller 33:13

And are all of these cycles, so we said menstrual cycles, who said postpartum, menopause, et cetera. Are all of these actually going through the same brain pathways that we discussed earlier?

Dr Emile Radyte 33:23

Not exactly those, all of those will have some sensitivity to estrogen or progesterone, which are the main hormones governing those changes. But those changes are a little bit different. One, they're different between themselves, but they're also different across women. It's also for example, your menopausal journey and what happens in the brain will depend on whether or not you've had kids and how many kids you've had. So, those are like a lot of the variations as well as family history, but high level, what we do know is that there is that alpha prefrontal asymmetric at the neural network level does seem to happen in all of them. And the way we know that's the case before we had the signs that validated and proved it is because of those symptom profiles. Because it's not like everybody experiences one symptom very consistently. It's specifically the fact that it shows that dysregulation of emotional control in all of those phases. And we just think that's primarily linked to progesterone sensitivity, but it has been shown to be linked to more of the estrogen changes as well. So at the electrical level, they're very similar. If you try to resolve them at the hormonal level, it would be much more complex and much more case dependent.

Judith Mueller 34:28

We've mentioned quite a few things, including endometriosis. Obviously, PCOS is something that's very common as well. Is that something that would respond as well?

Dr Emile Radyte 34:35

Yeah. PCOS is an interesting one because it's where obviously brain related signals mean a change in hormones. So in PMDD and endometriosis, women with these conditions often will have normal hormones, so they would always be pushed to go to an endocrinologist, get tested, and then realize that, great, my hormones are fine. I still feel these symptoms. PCOS usually there is an actual hormone culprit that explains some of those symptoms, but they might still experience it. When it comes to our devices, yes, as long as you have PCOS and mood and pain related symptoms, there's no reason the devices wouldn't work for you. In fact, we have lots of users with that. It's just that every case of PCOS is quite different, so it's easier to be like, a lot of people with endometriosis will use it for pain symptoms. PMDD for mood symptoms, PCOS, the profiles are very varied, but yeah, as long as you experience the symptom. We would personalize it based on that. And we do ask you to tell us that you have PCOS, so we could adjust accordingly. Especially because women with PCOS have quite irregular period, so we need to take that into account, but we can certainly adjust accordingly.

Judith Mueller 35:34

That's actually another question for people with irregular periods. It could be coming off a pill, it could be postpartum, it could be PCOS.

Dr Emile Radyte 35:41

Stress life,

Judith Mueller 35:42

How?

Dr Emile Radyte 35:42

I.

Judith Mueller 35:43

Yeah. Apart from that, how do you actually know when you are in your luteal phase? Because unless you actually feel your ovulation with, I guess most people don't necessarily do, or not all the time, at least, how do you know where you are?

Dr Emile Radyte 35:54

Yeah, the amazing thing about building in, 2025 is that we have amazing technology to support us. So on the one hand we can do tracking as good as any other kind of menstrual tracking app and do accordingly. We also integrate with any wearables if you are wearing them. So specifically temperature and basal body temperature tracking is an important way in which we can help you determine whether you've ovulated and a little Bitly. Most importantly, one thing that I really advocate for women is that. People always look to find an authority like my temperature jumped and therefore I ovulated, and things like that. Women are the expert of their own experiences and actually our symptoms and patterns are quite repeated. And so if you were to track your symptoms, you will often notice like a change in motivation around your ovulation or that suddenly after you've ovulate, you feel more low or more sensitive to specific things. And I actually think that if you track them reliably, those can become great predictors. We actually take your symptoms as your prediction as well in the samphire app, but it's also something you could do with, in a very low tech way. And the number of women I have seen with their Excel spreadsheets where they have figured out that pattern is very good. But yeah, for most women, you can track basal body temperature, you can track the dates if you're regular. But if you're irregular, I actually think that tracking those symptoms is really important. And one of the things that we actually added into the app after speaking to a lot of women with irregular periods in particular was adding any symptom that you feel is relevant to you. So we don't tell you what is right to feel. So a lot of women we're putting in weird things like nosebleeds always happen on day 17 of my cycle or wanting to break up with my boyfriend or things like that. And they're very particular to you, but they are? repeating and so you need to put in, so whatever feels legitimate to you or feels worth tracking, I feel is worthwhile and then we can trace it back. But to your point also, there is a proportion of population of women, we believe 20 to 30% who can physically feel their ovulation. And it's called middle schmertz or like middle pain from German and actually an international word. But yeah. And we do notice quite a few women experience that as well. And with PMDD, obviously we know that once you ovulate your symptoms start, so women with PMDD are hyper aware usually of when their ovulation.

Judith Mueller 37:56

Okay. And what would you say are the three most common user mistakes around timing, dose, et cetera, when people first start and how can they avoid it?

Dr Emile Radyte 38:06

I think all three go back to irregularity because we operate on the principle of neuroplasticity, so we're not adding something to override it. It's very important that we retrain your brain and it's missing one gym session is probably fine. If you miss a week, it's not gonna be great. So consistency is key. And we're always working alongside users to make it a little bit use easier. But as long as you use it consistently, we see really good results across the board. And I should mention that all of our devices come with 90 day returns.'cause our idea is we want you to be consistent and we want you to be able to try it out for three months because we know how well it works when you stay consistent. So I think that's number one. And then two, and that's probably the other kind of piece of the puzzle, is you need to know why you're doing it. And that's why we actually developed the app and understanding your cycle in that a lot of women might be like, oh, but PMS doesn't impact me. And then they start tracking and realize that there's actually a pattern there. So we think that actually understanding what your pattern is, what you're trying to fix, and how. Really empowers you to stay consistent because then you can see the improvement in those specific symptoms. And where we've seen people drop off is because they were like, oh, this doesn't impact me. And then their symptoms keep coming back and they don't know why. But once you start seeing that pattern, it all flicks into space. So I think these are the two pieces of the puzzle. And then, the protocol itself is very individual, so you know, there it's up to everyone. But as long as you stick to it? And you iterate accordingly and stick with it and are committed to it, it usually tends out to be great.

Judith Mueller 39:29

And there's actually so much benefit to having that data. For example, we've got an earlier episode that came out from Phase.io. So basically that's an app and or integration with your computer. So this is a productivity tool and basically based on where you are in your cycle, you have six different dimensions and you figure out my superpower in this part of the cycle is actually, it could be energy, it could be motivation, it could be the fact that I'm actually more critical, a bit more aware of finding mistakes, et cetera, which can, if you use strategically, can actually be a bonus. So I think there's so many different ways we can look at things. I highly encourage everyone to track. Speaking of.

Dr Emile Radyte 40:05

the only thing I'll add there as well is that's why I struggle sometimes because science can be very helpful to give us generic patterns and what tends to impact everyone. But if I've learned anything working in the space, is that everyone's experiences are so individual and it a lot depends. And I have met quite a few women who are like, around ovulation, I'm supposed to be at my peak, my most social and do all of those things, but that's not the way I feel. And a lot of women with PMDD feel that way because they're about to go to that depressive phase. And so I also think that, obviously. Take advantage of all of those tools that are educating you about it, but you are the expert of your own experience. And so I think the most important thing is you creating your own data set for yourself and your own truth as opposed to deferring what quote science says. Because while science can be great, it didn't look at your brain specifically, your history and your hormones and particular, and we still don't have the tools to integrate that data. Multim, modally, like even if you looked at hormones, pretty much no one can do a panel from the brain to the hormones to how they all link together and how they are impacted with your own individual experiences. So remember, you're still the expert, even if someone's telling you should be feeling one way or another,

Judith Mueller 41:07

I think hyper individualization is very important in any sort of biohacking, health optimization. I think especially for women, just because, as you said, there's so many different cycles, so overlapping.

Dr Emile Radyte 41:17

100%.

Judith Mueller 41:17

stick with the science. Tell us about the trials that you're running.

Dr Emile Radyte 41:20

Sure. So obviously we have some medical devices, some wellness devices on the market, and all of them have had prerequisite clinical trials in order for me to be able to sit here and say that they for sure improve mood and reduce pain. But part of me being a neuroscientist by training and spent most of my life in academia is that as a company we are. R and d first and foremost. So we continue doing a lot of innovation in different areas of health. Most of our research topics emerge from what people tell us. If there are listeners who have been using our devices or are considering using them, do let us know as well, because we always listen to that. For example, in the first year since we launched Nettle, which is our medical device for PMS and menstrual pain, we had a lot of people report improvements in migraines. So we actually are just starting a study now in migraines trying to understand how people with chronic migraines actually respond to nettle and those devices and try to find a good recommendation protocol for them. So that's one of the studies that we're running. It's more exploratory to add on, but again, came from user feedback. We are running two studies in endometriosis, one in the UK in the NHS and one in the us. Those are focused on chronic pelvic pain and endometriosis. This emerged from the fact that, a lot of our users, as I mentioned, use the device for pain relief, but then they realized that they also, in order for us to scale it up, we wanted it to be reimbursed so accessible to all the women who need it. Obviously there is a financial barrier to any type of technology nowadays, and in order for that to be the case, we need it to show integration with healthcare systems. So that's what we're trying to show right now, that it essentially not only makes women feel better, but also saves money for the system, which is one of the main outcomes that insurers and reimbursers are looking for. And that's focused on making our device more accessible to particular groups with particular diagnoses. We are just in the final stages of completing a study specifically on PMDD as well, which was a three month study. That's very exciting for us because a ton of our users with PMDD have benefited from YL already. We just wanted to have a clean study for them to reference into, because our initial study was focused on PMS and 44% of those women also had PMDD but they weren't specifically recruited for it, so we wanted to do A-P-M-D-D specific study. And then we have a couple of other areas of interest that have been brought up. A lot of our users have ADHD that is comorbid with other conditions. So we're looking to kick off a study there very soon. We're looking into fibromyalgia and other forms of chronic pain which have also been reported improvements. Again, it's not a fix all, but there are a lot of specific solutions, specific conditions that are related and disproportionately impacting women because they have some hormonal sensitivity, including fibromyalgia, migraines, which predominantly impact women. And so we're looking to use our clinical trial kind of strategy and data in order to push that further. And I should mention that for the vast majority of our trials, those are collaborations with academics. Or with hospital centers as well. So we usually try to make sure that the data is as independent as it can be and collaborate with kind of academic partners to analyze, recruit and keep ourselves out of the way while enabling them access to our technology and research tools.

Judith Mueller 44:12

I appreciate his early days. Final results are not out yet, but what sort of pain and mood responder rates are you seeing so far?

Dr Emile Radyte 44:19

So on our kind of basic device in clinical trials, we see that about 80% of people respond within a single month, and about 89% of people respond within three months, which is why that's where we go with the returns policy as well. We obviously want that to reflect our clinical evidence. The average change within a month is an improvement by about 67% on mood scales. So you can expect your mood to be about two thirds better than it normally is. And then for pain we see an average improvement of just about 50% within a month, and then climbing up rapidly to about a above 80% within three months or so. Again, this all comes down to that pain sensitivity threshold because there are some people for whom, it will always stay at some lower level. But it's a difference between taking 10 painkillers in one or, and for some people it will disappear altogether. We actually ran a fascinating study over the last month where we asked all existing users of our devices how essentially their interaction with medication and the healthcare system has changed since they discovered and started using the device. And the data was very fascinating because essentially it showed that I think 87% of people reduced their use of painkillers, so either reduced or completely eliminated the painkillers they use around their menstrual cycle. 25% of them changed the way they use hormonal contraception. So usually going off of it completely becoming an option or for example, reducing their dose of HRT and things like that, correlated to it. And then 22% of people change the amount of antidepressant dosage they needed as well.'cause oftentimes they might, again, brain stimulation doesn't interfere with any medication, so you can still use it safely alongside. But we do notice that naturally a lot of people either notice they don't need additional support or can tolerate lower dosages and therefore reduce their dependency long term.

Judith Mueller 45:58

So flipping back to the HRT, this will be menopause related.

Dr Emile Radyte 46:01

Yeah, this would be perimenopause, menopause and sometimes also PMDD related. A lot of women with PMDD go on earlier. Chemical induced menopause as well.

Judith Mueller 46:10

Okay. And you've mentioned the ADD link before, which is particularly interesting. Can you tell us more about that?

Dr Emile Radyte 46:17

The a DG clinical trial.

Judith Mueller 46:19

Yeah. In a sense of how does that fit in? Because the other ones I've seen more as physical conditions, some, so a DD doesn't seem to fit into that, if that makes sense.

Dr Emile Radyte 46:29

No, a DD is mostly linked with the PMDD bits. So essentially women with A DHD are at about three times higher risk of experiencing PMDD as well. And in general, we see that women or people with cycles experiencing a DD are likely to see worsenings, what we call premenstrual exacerbation in the weeks leading up to their period. And yet their doses are not adjusted. So this actually came from a lot of work that was done on seeing that if you're, let's say someone with a DD and you're medicated and that's working well for you, for many women, you might actually become underdosed in your luteal phase and start symptoms C popping up and then you go back again normally, because as your brain is changing your essentially dosage needed should change as well. But obviously. For most people who have a DAD and have had medications, I, bet your psychiatrist didn't ask what phase of your cycle you were in and adjust your dose accordingly. And the reason it's believed to be linked to these mood disorders is actually because the key node in ADD that is responsible for kind of managing the shift between the attention network and the DMN or the default mode network is in the dorsal lateral prefrontal cortex. And that happens to be the exact spot that our device stimulates in the prefrontal cortex in order to create that balance. So that's why we actually see that as we improve PMS symptoms, we tend to improve a lot of ADD symptoms. We don't know if that's specific to us improving a DD, and that's what the study is gonna tell us, or whether that's just linked to the fact that by reducing the premenstrual exacerbation itself, we allow you to mask it again in the way that it's managed in other phases of the cycle. And so the study is supposed to distinguish, is that affect ADD specific? So could we be an ADD treatment itself or is it more that for women who happen to have ADHD and then have like other conditions. The net effect is improvement in a DD is just not specific. Yeah, it's a fascinating link and I have met so many women in the overlap of those conditions, and I think it wasn't spoken about enough.

Judith Mueller 48:15

Speaking of responders, do you see any re patterns in Responder Best, for example, PMS versus PMGD or higher baseline pain versus milder cramps, et cetera, et cetera?

Dr Emile Radyte 48:26

Not really. We see actually that as long as there is some form of linkage to hormonal change, the patterns tend to respond quite well. They're actually quite severity independent, relatively. And the main reason for that is, if you imagine a painkiller, if you have more of those prostaglandins coming to you, you need more of the painkiller to connect and, annihilate those molecules. But if you're changing the threshold, it doesn't matter. there's five molecules under the threshold or 15 because the threshold shifted. So we actually saw that, people with very severe endometriosis related pain saw as good of a response as people with very mild pain because as long as their threshold response, then that effect is more generic. The one group that I probably wouldn't really recommend necessarily to is we do see a lot of people with complex conditions and complex overlaps are fines such as A DHD and PMDD endometriosis and EDS is another, for example, very common condition and like things across the board, but there are some people where they might be experiencing a lot of other conditions as well. And so for those people we noticed that even if the device helps improve their mood, if they still have a lot of those other physiological constraints, then oftentimes the change is just ultimately potentially not worth it. Just because it's like fixing one problem when they have 50. That's obviously unfortunate and those are usually more. Complex cases, not in terms of severity, but in terms of the combination of things that one might have. But a lot of people find that, you will need composite treatment anyway, so then you can manage some symptoms with drugs, some symptoms with brain stimulation, some symptoms with something else. So I think it's all a bit of an individual cases and we always speak to people individually about their needs as well on our support channel as well. And whenever we can give perspectives or speak to their doctors and provide them just context about the technology as well and how they want to integrate that in the treatment profile, we're very happy to do that.

Judith Mueller 50:13

Fantastic. And let's look at the devices from the user experience. So you've got this beautiful headband and what do you feel? What sensations is a painful, tell us more about that.

Dr Emile Radyte 50:26

Yeah, so essentially you take it out from this beautiful box and it's a travel case based on user feedback now, because a lot of our users do need to use it a lot of the time. And then you insert four sponges and you walk through that entire process. So essentially put in little sponges that allow us to create a connection between the device and your scalp. They're usually dry by the end of the session as well. Then you put the device on, it looks just like a beautiful headband and it connects to your app via Bluetooth, so it's usually a very smooth experience there. Then you go through what's called a tingle test. So essentially we make sure that there's enough of the connection between your scalp and your device. Usually during that time, people don't really feel anything and then the session starts. And during the session about 50% of people are gonna feel about a tingling or itching sensation is how people describe it. If anyone's ever experienced brain stimulation, all of them feel similar, but it's like this feeling of having your nails a little bit into your head a little bit prickly can be. And that's where about 50% of people, 50% of people will feel nothing. And in fact, for those who feel nothing, we always are like, Hey, your stimulation is ongoing. Everything's okay, just because then they get worried that nothing is going on. But yeah. So 50 50 in terms of those initial feelings, you feel usually goes away within five minutes. So within five minutes you usually get adjusted to it. And by the way, all of the sensations you're feeling, and the reason why a lot of people don't feel them are dependent on skin sensitivity. So it's not your brain responding. In fact, the brain has no pain receptors whatsoever, so it can't feel anything. But it's essentially just how sensitive your skin is. And sometimes we notice that you're likely to be more sensitive if you have drier skin or let's say as the weather turns and it's like darker and drier. Your scalp might just be a little bit more sensitive. But yeah, other than that, it's just inter-individual variability and skin sensitivity. And within five minutes all of those sensations are gone and you just move on with your life. If for some people you still feel them ongoing, you can push it down and then it feels quite comfy. At the end of 20 sessions, the headband vibrates and turns itself off. You get reminders when to use it again based on your individual protocol. We ask you to kind of rate sessions and give us any feedback for those sessions as well. And as I mentioned on the app, because we know your cycle or whatever cycles are overlapping, we can also recommend appropriate content. So let's say you are someone with PMDD and A DHD running a session in your Luteal phase, we might suggest you read our deep dive about the neural networks involved with that. Or just do a breath work exercise that. allows you to control your attention patterns. That might be all right during that time. And you can pick and choose your adventure or just watch tv, whatever brings you joy.

Judith Mueller 52:53

Are there any contraindications?

Dr Emile Radyte 52:55

Yes. So at the moment you shouldn't be using the devices and in fact, no brain stimulation whatsoever for people under the age of 18 and women who are actively pregnant for a device. Obviously we, oh, we actually do have an ongoing trial supposed to start in teens because we do hope to show that safety profile there. But for the moment, being under eighteens are not allowed. And then for pregnant women, obviously they don't have cycles or not cycles the way we see fit. We do hope that's another population where we can gather enough safety data soon, because we do know it could be an amazing area, especially for women who need to discontinue antidepressants while they're expecting. And, then the last bit is if you do have another implant in the brain. So if you do already have an electrical implant in the brain, we don't recommend you use it unless you discuss it with your neurologist essentially because you have two electric fields interacting. And so we don't know how they're gonna interfere. So obviously a bit extreme but that's an important one.

Judith Mueller 53:48

And what are the specific differences between the nettle as a medical device and the lutetia as a wellness product?

Dr Emile Radyte 53:56

So the main difference is the markets in which they're available and the claims they're making. Nettle is available across Europe and the UK because Europe and UK authorities have reviewed all the claims we're making on the device. And we can say that it helps with pain and mood symptoms related to menstruation. Lutia as a device that helps with general kind of hormonal balance and balancing out those hormonal changes is not a medical device and is not reviewed under the FDA. That's for a lot of different reasons. We will have another product in the US that is a medical device called Nettle Endo that will focus on endometriosis related chronic pelvic pain. The main reason for that is that PMS is a condition is still not diagnosable and is actually not considered medical in the us And so essentially it's considered a wellness condition in the us whereas in Europe we agree that if it's something reliably occurring and impacting your quality of life, it is more in the medical space. But that's more a kind of regulatory decision rather than anything else.

Judith Mueller 54:48

So the underlying device is essentially the same. It is more what you can actually say in each market. Obviously a big medical disclaimer here.

Dr Emile Radyte 54:55

The technology

Judith Mueller 54:56

come,

Dr Emile Radyte 54:56

the devices are different.

Judith Mueller 54:58

There. Okay, fantastic. So we've got lessers with hormonal contraception or with IUDs, either hormonally or non-hormonal. How does that work? And also you've got other medications. For example, we've mentioned the S-S-R-I-A lot. What are all these different interactions?

Dr Emile Radyte 55:13

Yeah, great question. So brain stimulation itself will not interact with the hormones or any other medications that you are on. That being said hormonal medications in particular will impact with the way your cycle presents and your symptom profile might shift. The way that we deal with it is on a case by case basis. So for example, if you have an IUD, some people will still get regular cycles. Some people will have no cycle at all, and some people will have. These weird suppressed cycles where they get a period every weird amount of time. So we take that into consideration as we design the solutions. And the protocol for them. For most people with hormonal contraception, that will mean that they're on this loop where we make sure that they get enough brain stimulation to feel imbalance and have that emotional regulation throughout. But also we can't exactly tell when their period is coming up. So it might just mean that instead of feeling the effects within a month, it might take three months until you see that effect because we can't time it to the right time, right place as well as we would if you had a perfectly regular cycle when you exactly when your period is happening and things like that. Obviously because usually most people get withdrawal bleeds, and same with things like HRT, we just look at what the profile is do you have a bleed? Just because bleeding is a very good indication that your estrogen and progesterone are low. So it's a good baseline quote, but we can work off of other data and that's where the. Symptom tracking really comes in because most of our users who are on IUDs or on hormonal contraception, they will mostly come to us for mood management symptoms as well.'cause usually they don't have periods that are severe enough or regular enough to cause regular management. And so then we try to understand, and, a lot of this is automated, but we also give personalized advice if needed. Essentially what are your mood related symptoms? How frequently do they occur? And a lot of people notice these like weird patterns where you might have mood symptoms twice within one cycle because the cycle is this like suppressed form of hormonal interactions? as well. But yeah, other than that, it's just about adjusting and finding the right frequency for you. but hormone responses are also so different, so we just make sure we customize it.

Judith Mueller 57:11

For someone who wanted to get this device through the reimbursement pathway, so specifically uk, and I'm guessing Europe to some extent as well, at least in the future. How do you have a constructive conversation with your GP gynecologist psychiatrist, without being dismissed as a gadget?

Dr Emile Radyte 57:29

Oh. I think having that constructive conversation isn't hard because we're a certified medical device, so we are on medical device registrations we can be prescribed. It's just the problem is that the government in most places won't pay for it. Some employers will already pay for devices like nettle for it to be reimbursed. I think the bigger problem is actually getting the whole issue itself dismissed. Like I think a lot of people notice that when they go to the doctor and complain about these issues is that the issue gets put away. But I think all of our work, in running clinical trials, validation and things like that has been that we're not perceived as a gadget. We're just perceived, to be honest, we're the only hormone free option for these people.'cause other than that, you just go on IUDs and pills and maybe antidepressants and drugs and things like that. So we haven't actually seen that problem with the medical community. I think more of the problem is recognizing that this is serious, number one and two, getting them educated because the problem is that. of the issues that we spoke about today. They're so interdisciplinary and most people who are become experts on them are actually the patients themselves. They usually know a lot of things better than their doctors, unfortunately, because it requires, going to an endocrinologist potentially who tells you that your hormones are fine. Going to a psychiatrist who says, because you're a woman, it's a gynecologist issue. Going to a gynecologist who says that because it's a brain issue, you should go to a psychiatrist, and all of these systems don't talk together. So I think the single biggest thing that I would recommend for people who are exploring or have these issues due is if you do notice these devices and you're able to try them out yourself is mentioning it to your doctor, because we now get a lot of clinicians reaching out to us. With interest to learn more about the device because a patient mentioned it to them and then we send them our data packs and then they actually read them. Because we noticed that when we were just going and trying to educate them about it, they said that the patients don't have that as a problem. And we were saying that, the patients don't tell them that's a problem because they felt dismissed. So it's more about just spreading that word. But generally I will say that at least in my experience, the clinicians given the fact that, we have the data around it and we do have the certifications around it, that hasn't been an issue. And most clinicians want to give people an option, but the only option they can point to is either unvalidated vitamins and things like that. And obviously, like it's great for people to be able to try out different things like, and different things might work for different people. But the point of being a certified medical device is that we work for the average person reliably every single time and is better than alternatives. And that's the promise we make. And and I think doctors are very keen for that.

Judith Mueller 59:48

Let's see where the future takes us. Speaking of, I think we've dug quite deeply into Sunfire. Thank you for that. Are you ready for the curve ball questions to actually meet Dr. Emily in person? Fantastic. So number one, what are the three things that you wish your colleagues and or clients would know that you believe would really move the needle in your field? And obviously, one, we've just talked about education, but.

Dr Emile Radyte 1:00:11

Yeah, education, which comes from that first one is more like formal, just knowing things and having exposure. But number two is that you're the expert of your own experiences. I feel like I beat that bush so many times, but I think that's so important because so much of my field, and by my field, I consider neuroscience, women's health, and the overlap of the two. So much of that field hasn't been able to grow because so few women's experiences have been documented. Like a lot of the work that we did day in, day out with brain stimulation was actually just listening to women's experiences, trying out different protocols and figuring out how specifically we adapted to specific circumstances. And the only way to do that innovation and that work is by women. Recognizing what they're feeling and sharing what they're feeling as well, because then we can actually use that as data points. So you are the expert of your own experience. Whatever you're feeling is legitimate and if you can find a way to track it, be that on our app or your Excel sheet or paper, that's really important. And then finally the last one would be, which probably is, goes beyond my field, but I think definitely relevant in it is that you are the one in charge. I think that a lot of people feel that when it comes to hormones or their health and obviously fewer biohackers who want to take control of that health, but a lot of people feel like they're destined to a particular path. Like they were stuck on a bad diet and they can't be fixed, or they were smoker for such a long time and they can't quit. And I think with any type of intervention, and especially with hormones, when you feel like they're controlling you and your mood, a lot of what our devices and our solutions and our education is trying to do is tell you no. This is up to you. Your hormones might be changing in a way that's hard to control, but the fact that your hormones change doesn't mean you can't control your brain anyway. And your response to it and your response to those experiences. So the fact that you're in control and you have agency is my number three.

Judith Mueller 1:01:54

I think that there's actually two sides of that coin. There's the opportunity, you are on charge. You could, you can actually take charge. But I think there's also the responsibility because the average GP has something like six minutes per patient. It's not very different from the psychiatrist and the gynecologist. Unless you're the one actually taking charge, no one else is gonna be able to do that for you. What is the book or books that you've given the most as a gift? Or what are the books that greatly influenced your life in one way or another?

Dr Emile Radyte 1:02:23

Oh, this is a great one. So there's the Caroline Creto Paris, the Invisible Women. I think it's probably one of my most kind of professionally gifted books as well. The reason I like it someone put it very neatly, is that it brings all the facts about women's health and present them in a little bit of a male way, very clearly that it's not. Female health experience centric, but like all the facts, I would recommend every woman at least skim through it. That's essentially all of the facts that kind of go through that life. And I think it just emphasizes how much of the unseen is out there. And then other than that, I'm actually a fiction reader. So I always found that, I read textbooks in very deep scientific work, and then I read fiction. And I find that the balance is very helpful because in my fiction I like to see stories and how they integrate different facts around them. And so I have found that the most influential in terms of seeing those stories around.

Judith Mueller 1:03:12

Anything particular that stuck with you?

Dr Emile Radyte 1:03:15

Not recently. Not recently,

Judith Mueller 1:03:18

Okay, there's a call to action to all the writers out there. Get your game on.

Dr Emile Radyte 1:03:21

I'm ready.

Judith Mueller 1:03:23

What purchase of a hundred dollars Euros or less has most positively impacted your life in the last two, three years? Or say in recent memory?

Dr Emile Radyte 1:03:32

Oh, I think obviously since Nale my oura ring, I love the fact that it now integrates with it and I

Judith Mueller 1:03:38

i.

Dr Emile Radyte 1:03:39

We speak a lot about the fact that you need to integrate across your full stack of metrics. And taking control is one step of it, but tracking your body is another. And I. think the oura ring is particularly well suited for women. In particular, I think both the form factor as well as the basal body temperature tracking and all of those sensitivities. So I think it has made a big difference for me. I loved it. And we integrate with all wearables as well.

Judith Mueller 1:04:02

The interesting thing they've just raised just it was a couple months ago, they've raised 200 million on a 5.2 billion valuation. For those out there who are not necessarily in the field of fundraising, that's a fuck load of money. Excuse my French. They're actually using a lot of that for AI development, but they're also really passionate about women's health. So I think there's gonna be some interesting things coming out there.

Dr Emile Radyte 1:04:22

think for me, when I hear those, facts about both the money and scale, it's like when they started for a very long time, they were relatively slow because everybody said that one hardware was dead And hardware was hard as an investment. But two, that people wouldn't care that much about their health and wouldn't invest as much into it. And so I think as someone building hardware for women, which like are both considered not cool areas, you don't wanna, as a business, you shouldn't go into hardware and as a scientist or whatever, you shouldn't go into women's health because women are a lost cause. To me, it's actually a huge beacon of the fact that no, no time has come. Women know this is real. They need real data, they need real facts, and we're gathering them from our bodies and now from our minds and experiences as well.

Judith Mueller 1:05:01

And if we up the threshold to say a thousand pounds dollars Europe, what has made the biggest impact on your life recently?

Dr Emile Radyte 1:05:10

Ooh, a thousand. What did I last spend must have been. My wedding rings

Judith Mueller 1:05:16

enough. So

Dr Emile Radyte 1:05:17

bit. Yeah.

Judith Mueller 1:05:19

something we can recommend. Okay, fair enough. Speaking of, what is one of the best or most worthwhile investments you've ever made? This could be money, time, energy, et cetera.

Dr Emile Radyte 1:05:30

The work we do with Sandfire every single day. I think as someone who, grew up in an academic framing around making sure that the work we do in Neuroscientific Labs gets translated, I think the job that I have as well as all the time invested, all the effort, all the, blood, sweat, and tears into it, those payoff every day, every time we hear like feedback from a user And kind of those impacts. And it's the most meaningful thing I have ever done and and will continue to do as well. I think it's fascinating and I would highly advise people to find meaning wherever it is. I think seeing that coming back has been amazing.

Judith Mueller 1:06:04

And what is an unusual habit or an absurd thing that you love?

Dr Emile Radyte 1:06:09

Ooh, unusual habit. I love? cooking. I don't know if that's an unusual habit, but I'm a stress cooker. Anytime I need to resolve an issue, I actually put my laptop away and I just bake. And I kid you not, it's not like baking one cake. I like might bake four until I resolve an issue, but usually I pick up my laptop and then I figure it out the issue as well. Yeah, it has been great. My family eats a lot of cake as a result.

Judith Mueller 1:06:36

I was just gonna say, you're a stress cooker. I'm a stress eater. I think this would go very well together, or rather not.

Dr Emile Radyte 1:06:41

match.

Judith Mueller 1:06:43

Okay. What are you working on at the moment or more relevant? What is the next exciting breakthrough that you can see coming? This might not be your own work. This might be something unrelated.

Dr Emile Radyte 1:06:53

Yeah, I think the next big frontier that's gonna unlock everything is having that like full stack understanding of women's health. And I don't necessarily mean that everybody needs to do like hormonal panels all the time or things like that, but it's understanding cause and effect in your everyday life. Because I think a lot of women feel like whatever factoid they get about their health is one piece in the puzzle. And then they need to find another one and another one. And by the time you found the last one, the first one has probably changed. And so I think once we have some way of doing three monthly or six monthly quick check-ins that just like look at the overall balance. But that goes from brain reactions to hormones to bodily composition, to things like that. I think that will unlock not only so much scientific knowledge, which is a nerd's dream, but on the other hand, solutions for women because the number of women I interact with every day. Who have figured out bits and bobs of piece of the puzzle and then their circumstances change. They get pregnant, they go through menopause. Something like that, just very frustrating as an experience as a woman because you need to always educate yourself and while educating yourself all the time is good. I do think making that easier and integrated will make a massive difference. And I do think that already, like I think Aura and Samphire are going one way. I think adding a couple more like biophysical composition measures, we take that another step as well. So I'm very excited for that and I think it's gonna be feasible within the next two years. It's more a matter of frankly, I think it's commercial feasibility. If we can do it commercially, we'd love to do it internally as well, because the tech is there. It's about putting the pieces together and having people who think in that way pull it all in one place.

Judith Mueller 1:08:25

I think it's very encouraging that the tech is already there in a sense that we crack the, I wouldn't say we've cracked the hard bit, but we've cracked the bit. There's where our knowledge is limiting us as opposed to the way that we collaborate as a society, which is, something we can figure out.

Dr Emile Radyte 1:08:41

Yeah, and as we like, we've cracked a bit on the composite parts as we pull them all together. We're gonna get more questions than answers, I am sure. But we need to put them together in order to get the next frontier of Answered.

Judith Mueller 1:08:52

last question for you. Who will be a perfect sidekick in your lab or your work? This could be someone past or present real or imagined, anyone.

Dr Emile Radyte 1:09:02

Ooh. Should have thought about these questions deeper. Perfect sidekick, honestly, like my current co-founder. He's the person I've worked with the best and know the best, but we also have very dense styles of working, so I'd probably pick him all over again because I'm always worried working with someone new, they could be an amazing person that I've heard amazing things about and that are so famous and things like that. But I think so many things come from synergy and being aligned and having complimentary styles. And there's just a person I know.

Judith Mueller 1:09:33

I think he'll be the first person to pin the episode. Fantastic.

Dr Emile Radyte 1:09:36

Exactly.

Judith Mueller 1:09:38

Brilliant. Emily, thanks very much for coming on.

Dr Emile Radyte 1:09:40

Thanks so much for your time and thanks for all your thoughtful questions.

1:09:55

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