Tired, anxious, gaining weight? It could be your hormones with Dr Helen O’Neill

Hormones influence every system in your body. If you feel tired, anxious, or are gaining weight, your hormones may be involved. 

In this episode, leading reproductive expert Dr Helen O’Neill explains how hormone health affects fertility, metabolism, and mental health for both men and women.

The core question is simple: if hormones run your body, how much influence do you have over them?

Alongside ZOE’s head nutritionist, Dr. Federica Amati, Helen explores the links between hormones and fatigue, anxiety, weight gain, fertility, and metabolic health.

The episode covers thyroid health, chronic pain, sperm health, and why gut hormones play a central role in appetite and weight regulation. We also examine why some female-specific conditions remain misunderstood or undiagnosed, and how better data may help change that.

You’ll also learn why changes made over three months may meaningfully influence fertility, and why conception is always a shared responsibility.

If hormones shape how you feel every day, what might shift if you supported them differently?

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Jonathan: Helen, thank you for joining me today.

Helen: Pleasure to be here.

Jonathan: And Federica. Wonderful to see you again.

Federica: Excited to be here, Jonathan.

Jonathan: So Helen, we have a tradition here at Zoe where we always start with a quick fire round of questions from our listeners with these very strict rules for scientists. You can only say yes or no or one sentence if you absolutely have to. Willing to give it a go?

Helen: Challenge accepted.

Jonathan: Alright. Are there any parts of the body that aren't influenced by hormones?

Helen: No.

Jonathan: Do women have testosterone?

Helen: Yes.

Jonathan: Do men have estrogen?

Helen: Yes.

Jonathan: Federica. Does what you eat change your hormones?

Federica: Yes.

Jonathan: Can body fat influence a man's testosterone levels?

Federica: Yep.

Jonathan: And Helen, what's your favorite fact about hormones? That still blows your mind?

Helen: I would say that the gut itself is like a hormone factory.

Jonathan: That's amazing. I'm still coming to terms with the fact that men have estrogen, which tells you how little I understand hormones. So I think we should start at the beginning, because we've already established that I have no idea what hormones are. What are they, Helen?

Helen: Our hormones are essentially like chemical messengers that are responsible for pretty much every aspect of our lives: our inflammation, our immune systems, our metabolism, our reproduction, our cognitive function. They are these fundamental and powerful messengers that are produced all over the body, whether it's individual organs or glands, or the traditional endocrine organs like our ovaries or testes, but also in non-traditional places like our gut and our fat. We are constantly producing hormones to essentially travel throughout our bloodstream to do various functions, but almost every function relies on hormones or a collection of them.

Jonathan: And why do we need hormones? Because we also have these nerves and my brain controls things. So why do I have hormones wandering around my blood?

Helen: I guess when we think about hormones, they're there to protect us to a certain extent. So the best example I always give of a hormone to give you an impact of just how one hormone produced by a single organ can have a multi-organ and systemic effect on you. So when we talk about our adrenal glands or adrenaline junkies, that is our adrenal gland producing adrenaline. Now, how do we get an adrenaline shot, or how do we get that kind of shock? It's if you see someone, so either a visual cue, you could see your ex. You get this jolt, you could hear something, it's a big bang. You get a jolt. And what happens when you get that production of adrenaline? Your heart starts racing. Your cheeks go red. Your blood is literally pumping faster around your body, and that's a protective thing. It's to get you out of danger. But equally, sometimes if you get a big enough shock, you might feel like you need to defecate. Pretty much almost every aspect of your body is responding to this threat. It may not be a threat, it may be something exciting, but regardless, what it's doing is it's telling you that actually one small hormone can go to the entirety of your body and affect your bowel, affect your heart, your breathing, your skin. All of these things are happening in that instant with the production of one hormone. So that is always the example I give, which gives you an idea of the power of one hormone, and you imagine the collection of hormones constantly working. They really do keep us going in both survival and just maintenance.

Federica: And I guess it's good to add here that hormones are tiny, tiny proteins so they can reach every single cell. Your nervous system reaches parts of your organs or the outside of things, but it's the hormones that reach every single cell at a cellular level. So that's why we do need them, because we need control of absolutely everything that's going on.

Jonathan: How many hormones are there?

Helen: Around 50 to 70. They are probably underclassified in women, but then there are hundreds of actual peptides and thousands of peptide signaling molecules. So these individual molecules that enable them to travel because when we think about something being produced, we also have to think about the place that it was produced and the surrounding architecture of what is needed to allow that molecule to travel around the body.

Jonathan: And I've already picked up from your example with adrenaline that my hormones are not all being made in the same place.

Helen: That's right. We have the traditional ones that we like to think of like your pituitary or your thyroid gland or your adrenal glands, or your testes or your ovaries. But also there's the non-traditional ones that we don't tend to think about, like our whole fat system is producing and receptive to hormones, and our gut is extremely receptive to hormones and what is in there enables us to produce either additional or less hormones, depending on what is in our gut.

Jonathan: I definitely shouldn't think about this as being there's one place in my body that's churning out all of these different hormones.

Helen: There's no individual hormone factory. No.

Jonathan: All these different places are producing hormones because they have different purposes.

Helen: Yes, they all have different roles, but I always think about our hormones like an orchestra. I often think that the thyroid is like the conductor of an orchestra. And when you think about each of the organs as being a musical instrument and each of the hormones as being the sound that they make, those hormones or organs can produce individual sounds, but collectively and together it can make for a beautiful symphony. But one. Playing a bum note ruins the entire song.

Jonathan: That's a beautiful image, Helen, so that you are painting this picture where hormones are central to how my body works. And they're very complicated and there are many of them. They're doing very different things. I feel like when I was brought up, some hormones were something that only women had, right? And that somehow women at least have more hormones or are more hormonal is a phrase that people say. What does that come from?

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Helen: We like to weaponize hormones, and I think it just stems from a complete misunderstanding of what they are. We like to use the word hormonal as being almost an insult when actually, of course, we're all hormonal. Our hormones allow us to know whether we're hungry. Whether we're full, whether we should wake up, whether we should go to sleep. Those are all very hormonal aspects of our lives that keep us going. But because there is a system-wide misunderstanding of what the role of hormones in our bodies play, we like to think of hormones as only being to do with reproduction. And we like to think of reproduction as only having a role with women. And when we talk about the changes that we see in our hormones, we often associate it with the menstrual cycle. And so therefore, it lends to this narrative that hormones equal reproduction or your menstrual cycle. And if your mood changes or alters, therefore you are hormonal. You are a victim of this hormonal cascade that happens to you every single month. And really it just comes down to ignorance.

Jonathan: So I think this episode is gonna focus mainly on research conducted on women. Yeah. I would like to ask one question about testosterone. Because there's been a 50% increase in men injecting testosterone in the US within the last five years. What is that about and is it a good idea?

Federica: I think men are way more aware now, and everyone is aware of hypogonadism. So this idea that men have lower testosterone levels. If somebody has been identified as having this low testosterone hypogonadism, which is something you have to do repeated fasted blood tests for to make sure that you have it, then testosterone therapy is really helpful. The problem is people are now seeking testosterone therapy when they don't have this low testosterone level, and actually, that does carry some risks.

Helen: It also has major risks for your reproductive function as a man. Because if you think that testosterone is largely produced in the testes and you are then injecting anabolic steroids and you're taking exogenous or external testosterone, your testicles think, I don't need to do this anymore. And they will literally stop producing testosterone. If you are, especially a young man, injecting testosterone, it leads to infertility. So it's really important to think of what your own testes are doing to produce and support your own basal level of testosterone. And when you say why? Because people are more educated now. We're able to disseminate information whether right or wrong, and information can land. And information around our health tends to be very polarized.

Federica: Yeah, and that's why measuring and testing your hormones is actually important, so you can understand what your baseline is and where it sits compared to what would be appropriate for your age, because then you can make an informed decision on whether it's worth intervening or not.

Jonathan: I'm thinking now, back to this discussion that we had a moment ago, talking about hormones and hormonal, and the other thing that we had a bunch of questions about is this phrase, a woman's biological clock. What does that mean, and what is it?

Helen: It essentially refers to the fact that, speaking of testicles, testicles produce sperm over a life cycle of about three months. So every three months, you're producing more sperm. On the other hand, for women, we are actually born with all the eggs we'll ever have. So the eggs that are laid down for us in our ovaries, they're called the primordial follicles, and are laid down when we are actually in utero. So when our mum is pregnant with us. That is when our egg cells form.

Jonathan: That's amazing.

Helen: So actually what your mum eats during pregnancy and what your mum has been exposed to, your mum's nutritional deficiencies impact your eggs. They impact your overall fertility. So when you're born, you're born with 1 to 2 million egg cells and you lose them over time. That is the idea that you have this biological clock that you're losing every single year. And I think people often put the emphasis of the discussion on this clock and time running out, but actually, what's never mentioned enough is the idea of egg quality as well. And the fact that if you think about bringing your eggs everywhere with you, then everything you are eating, are exposed to, are drinking also impacts your egg quality. Now, it might seem a little bit bleak to think, oh no, everything that I've done in my life is going to affect my eggs. But equally, when you think about all those cells, those egg cells aren't just ready to go and be released. They are primordial, they're in their infancy, and they still need to grow and mature within the ovary, and so what we do over the course of three to six months prior to getting pregnant is really important to the health of an individual egg, as we ovulate every month. Ovulation is the production of an egg that is released for potential pregnancy.

Jonathan: And then over time, the biological clock idea is there's this sort of shrinking number, and you're also describing the shrinking quality of these eggs over time as you slowly move towards menopause.

Helen: Yes, exactly. Where you have no eggs left at all.

Jonathan: So I think the two of you have painted a brilliant picture of just how important hormones are, and I sort of wanna go back, Helen, to your example of this orchestra where if it's all working together, it's playing this beautiful harmony. But you said if even one hormone is going wrong, then it's almost like this terrible noise that breaks everything out. Helen, what are the main factors that cause the orchestra to go wrong and these hormones to go sort of outside of the range they should be in?

Helen: There are so many different things that can impact our hormones, whether it is our external environment and stresses and when we are unhappy, whether it's in our work environment, in our daily commute, in our relationships, the stress of that actually does impact our hormones, and it does so in quite a significant way. The next thing that can impact is actual health conditions, so our reproductive health conditions, for example impact our hormones, but also our life stage. So we know categorically that our hormones are going to change as we go through life. The easiest example that we could all relate to in terms of being hormonal is teenagers. We tend to describe teenagers as being moody, spotty, and hormonal. They are, I guess, victims of that hormonal transition, and we allow for that. But we don't make the same allowances through other life stages. In fact, only now are we starting to make allowances for the other end of the spectrum, where we are witnessing this huge hormonal transition through perimenopause and menopause, and it's due to a lack of understanding. And then the third thing I would say is what we put in our bodies from a food perspective, some of our hormones quite literally cannot be produced without certain nutrients. So when I said that the thyroid was the conductor of this endocrine orchestra, we cannot make our thyroid hormones without iodine. And so, having an iodine deficiency, which is one of the most prevalent deficiencies we have, means that the conductor is sitting down. He's not sending anyone where they should be, what instrument they should be playing.

Jonathan: How can someone tell if their hormones are unbalanced, that this orchestra isn't quite playing right? What are the symptoms that I might experience?

Helen: The top reported symptoms we see are, I like to think we are failing. Fatigue, anxiety, irritability, low mood. It's not necessarily the physical aspects that we report because we like to think of our mental health as being above, and our reproductive health as being below, and everything else in between, but actually they're inextricably linked. Our mental health and our physical health are controlled and governed by our hormones. And if any aspect of our hormones is really subject to stresses like high cortisol, then we're going to see that throughout the rest of our bodies.

Jonathan: It's really interesting that you talk about this combination of both how I'm feeling in terms of my mood, but then also sort of these more physical effects, like I'm tired, and that they're all just linked together from the same hormonal thing. Because I was definitely brought up to say your mind, your body's separate and if you're feeling depressed, it's got nothing to do with being physically exhausted so that you can't walk around.

Helen: Yeah. And that's the problem. I think many of those symptoms are very insidious. How tired is anybody else? It's all relative to how tired the next person is, or even feeling cold. We all have different sensitivities to hot and cold. Men and women have very different sensitivities to hot and cold. And so when you have somewhat of a subjective and insidious nature to a symptom or how someone feels, then it's very hard to pinpoint it. And moreover, we self-eliminate from getting help. So even though you know you're tired, even though you know you don't feel great, we are the first person to blame. So we'll say, well, I didn't go to bed on time. Or I haven't been eating well, you'll look for a reason to blame yourself instead of saying, actually maybe something internally and physiologically isn't right with me. And therefore, and that it actually makes me quite sad. Thinking of people who live their lives potentially with just a small deficiency or something as simple as being able to fix their thyroid with iodine, it makes me sad that they could go almost their whole lives being substandard in what they actually are in themselves just because of a lack of understanding of the link between feeling tired or feeling low mood and our actual, the role that our hormones are playing in that.

Again, it's to do with your symptoms. Feeling tired, feeling cold, hair loss, weight gain, or weight loss. One of the most prescribed drugs in the world is levothyroxine for the thyroid.

Federica: As Helen mentioned, micronutrients are really important, so iodine is the most important and knowing whether you are getting enough iodine in your diet. Now the UK is one of the only countries that doesn't have fortification of salt as a public health intervention. So many other countries, table salt will have iodine added to it exactly to prevent this. But we don't have that here in the UK and not everywhere in the US. So different countries have different interventions. For example, if you eat no seafood whatsoever, you don't eat fish, you don't eat shellfish. Those are the main sources of iodine in our diet. So it's worth finding out, okay, what are my levels like? Is my thyroid struggling? So is it trying to stimulate TSH as a hormone? Is that really high? Because it can't quite produce enough of the hormones I need, and then you can look to either supplement or intervene before it becomes a problem, where medication is then needed for the rest of your life, normally.

Helen: Actually, iodine deficiency tends to get higher the further inland you go. The closer to the sea you are, the fewer cases you see, and then the further inland you go, the higher the prevalence.

Federica: And in fact, actually spending time by the sea, Jonathan, because there's so much iodine in the sea. When you spend time by the beach, you actually inhale iodine from the sea spray.

Jonathan: That's brilliant. So I just stand by the beach with my mouth open, and you can just breathe. Just breathe. Alright, then everything is solved. So, it sounds to me also as though you're saying, Helen, that there are fairly straightforward tests to understand the level of these hormones bscause you were saying, I think this is unbalanced. What's your next step?

Helen: The next step is to check your hormones. One of the most routine medical exams we'll do is to look at your hormones. I do wanna caveat hormones being unbalanced versus hormones being clinically outta range. There's a lot of online move towards balancing your hormones and what balancing your hormones means in that context is, say, I'm gonna use a male example rather than a female one. You have lower testosterone in the evenings. Eat something that would make your testosterone naturally rise. And so from a menstrual perspective, if we know that in the latter half of your menstrual cycle, you are lower in estrogen, people are saying, let's balance your hormones by eating foods or seeds that might mitigate that loss of hormones. So there's the difference between balancing your hormones and the idea that your hormones are unbalanced versus clinically outta range, which is still unbalanced when you think about the overall physiological. But I just wanted to take a moment to make the distinction between the two.

Jonathan: Do I want to balance my hormones, or the way you're describing it, sounds as though these changes during my day, or I guess as a woman during a month, are sort of natural.

Helen: They are, but for some, they can impact you a lot more than others. And so I think it does stand to reason that in the latter half of your cycle, your luteal, or we call it your luteal phase because you feel quite low during your luteal phase. You might wanna do anything to mitigate feeling so low.

Federica: Hormones are very tightly regulated and there's feedback loops for basically every hormone. The way that works is if one hormone gets sent out and it arrives at the destination, there's another hormone that will come back and say, hey, we've received this message. So we don't want people to think that they should be going out of their way to interfere with that messaging. So we see online going back to more dietary hormones. People talk about being scared of insulin, right? Oh, well, we don't want insulin to spike. It's like, well, you do actually insulin's super important hormone, and we are not trying to prevent insulin from ever being secreted, right? So there is, I think sometimes this narrative of balancing hormones makes it sound like you can just go in there and hack it and change it, but it's very tightly regulated. There's a lot of homeostasis, so keeping things balanced naturally. And then to Helen's point, when your own body's struggling to keep that balance, it can become problematic even before it goes out of range. And I guess we'll talk about some of the conditions where that happens.

Jonathan: Just before we move on to that, we had a lot of questions about weight gain associated with hormonal changes. Are people wrong to associate these hormonal imbalances with weight gain?

Helen: No, definitely not. Because as part of the signaling, we are now starting to understand what's called adipogenesis, which is our production of fat cells, and the idea that actually our fat in itself sends signals to the brain, which can send signals to our other organs to enable us to actually want to eat more or eat less. And so, the most common of metabolic conditions, is the first part of that feedback loop that becomes interrupted. And what I mean by that is if you have a chemical imbalance within your hormones and a metabolic dysfunction, your ability to either burn fat or continue to produce it is at fault. So one of the most prevalent metabolic conditions in the world is polycystic ovarian syndrome, which affects women around 1 in 10 women. And that's one of the predominant things that actually happens, that signaling process, both that goes to the brain and goes to the ovaries, has been affected through multiple different reasons. They call, we call it a three-body problem. When there's two things you can predict where they're going to hit. When there's three things, you almost can't predict where something's going to hit and when there's three systems at play, your ovaries, your fat cells, and your brain, it's actually quite difficult to predict what is going wrong and how to actually prevent it when it comes to. Polycystic ovarian syndrome or PCOS. But often one of the biggest complaints that women make is that actually from our data we see that it's low mood and depression, but from a clinical standpoint, it's weight gain and difficulty losing weight.

Jonathan: So you're saying PCOS, firstly, 1 in 10 women are affected by this, so it's very common.

Federica: Yes. And it's the most common endocrine disorder in women of reproductive age. So, more than type two diabetes, which is shocking, I think actually.

Jonathan: I don't understand, however, what's causing it, but what I heard you say is that it really does affect this sort of weight gain along with a set of other factors. Could you just help me again to understand a little bit what's going on here?

Helen: So what we know is that PCOS lends to hyperandrogenism, which means you have high levels of what are typically described as male hormones, which we now know are not. So your androgens are like your testosterone, and you have higher levels of those. And so what that lends to is from a reproductive standpoint, you have lots of these follicles. We said we're born with all of them. You have lots of these follicles, which are immature eggs, but they don't necessarily reach, they don't get enough signal to mature fully, and so you don't actually necessarily every month release a mature egg, which means you don't ovulate. And so there's the hyperandrogenic aspect of PCOS, meaning you have higher levels of testosterone, which can lead to excess facial hair. It can lead to loss of hair on your head. But also then you have the ovulatory part of it, which means you don't release an egg and so you become anovulatory. And so that means it's affecting your physical health, your appearance, but also your reproductive health. But because of the high receptivity of all of our hormones in our brain and the hormone receptors in our brain, it also significantly affects our mental health. So it really does impact so much of our lives and is so prevalent. It really is unfair how misunderstood it is when you think about how much research and funding goes into type two diabetes. And yet no funding goes into PCOS.

Federica: Yeah, it's a real hormonal syndrome and it affects risks later in life. So a woman who has PCOS, for example, she's three times more likely to then develop type two diabetes later in life. So it's a risk factor as well as being a syndrome in itself. And as Helen said, it often affects weight. So women put on a lot of weight and then that changes their metabolic health. So there are hormones that are involved in signaling from fat, to brain, for example, leptin, they're disrupted. And the gut hormones that are involved in signaling for satiety and for fullness are also disrupted. So we'll get to the solutions later, but some very interesting research, Jonathan, looking at how you can actually really improve PCOS symptoms and outcomes with dietary intervention.

Jonathan: So it sounds pretty severe from the way you're describing it, and also really common. Do we understand why your hormones are being disrupted in the first place if you're ending up with PCOS?

Helen: There are a number of theories. Some say that it is due to androgen exposure in utero, so it stands to reason what I mentioned, about all our eggs forming when our mother is pregnant with us; they say that higher levels of testosterone exposure while you are forming could be one of them. They also say that it is passed on. The paternal side suggests that there is actually a male phenotype for PCOS. But no, we don't fully understand what causes it.

Jonathan: So why isn't it better investigated?

Helen: Ah, it's just that 50% of the planet that we didn't bother creating any medical solutions for, including any clinical trials or, just innovate generally towards women.

Federica: Until 1993, women didn't have to be included in clinical trials. So before 2000, about 80% of all drugs that had to be removed from the market had to be removed because of the side effects on women that weren't accounted for. They had to be completely removed. Now, since 93, you have to include women in trials, but we still have some blockers where the researchers then don't necessarily actually look at the data and separate men and women in their analysis to understand the differences. So we're still sort of playing catch-up to medical science actually involving women and including them all. A lot of the research also, didn't include women because we were worried about the effects of the menstrual cycle and the changes in hormones. So PCOS, which directly affects your menstrual cycle and hormones, is one of the reasons really why women were excluded from medical research in the first place, and now there isn't so much investment in it because as you said, lots of reasons. But it's one of these syndromes that are so complicated for etiology and treatment that I think it's made it difficult to make it a really strong proposition for furthering research. Unlike, for example, cancer, which obviously gets a lot of research. I think things will change. I think things are changing slowly, but it's taking quite a while for endometriosis and PCOS, which endometriosis is another condition, which is massively impacted by hormonal health.

Helen: When you think about conducting a clinical trial. And wanting to ensure that everyone is at the same stage, we tend to, even when taking blood, you say come in the morning when fasted, and that's so you are not interrupting all of the daytime hormones that start to kick in or your blood result isn't impacted by what you've eaten. When you think about the huge change in hormones, I call it a very complex calculus of hormones that change every single month in women. In order for us to understand and not be subject to the changes, you would want to take a blood sample from a woman, from every woman in your trial on the same day, and that is on the earliest part of their menstrual cycle before all of your hormones start to really cycle in order to create and release an egg. And so, capturing enough women at that one menstrual time point is actually technically very difficult to do. And it's meant that even in preclinical animal studies, we exclude female mice or models from the experiments that are done. So, can you imagine trying to capture women at scale and they're all, they all have to be on the third day of their menstrual cycle. It almost seems impossible.

Federica: And then with PCOS, where you have often very irregular periods, it'd be even harder to guess when that would be.

Jonathan: That sounds like a really interesting way to ask you about your research into reproductive hormones at this company, Helen, that you've built, because I know you've now tested the hormones over a hundred thousand women.

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Helen: Yes. I think when we started, it actually started as a clinical trial. So that we could better understand the role of our hormones and our symptoms in different reproductive health conditions. So when I said it's almost impossible to capture women at scale on the third day of their menstrual cycle, that's exactly what we've done. So we've done that by enabling at home testing as opposed to physically needing to go to a clinic. So if you think that actually, if you only contest on the third day of your menstrual cycle, you only have 12 of those every year. Fewer if you have PCOS. And so by removing that barrier to entry and enabling somebody to do a blood test from home on the third day of their menstrual cycle, irrespective of where they are, really means that something that seems so simple from a global data standpoint has been transformative in unlocking one of the most underserved areas of medicine there is and has enabled us to create the richest and largest data set of its kind.

Jonathan: What insights has this data given you about the reality of women's health in 2026?

Helen: So many insights and actually what we see is that women of today are not the same as women of yesterday and decades before. And when the books were written about women from decades ago, those women weren't exposed to the flippancy of alcohol that women of today have. The change in smoking habits, vaping habits, the change in our daily exposures to chemicals that literally disrupt this whole orchestra. Chemicals that are in our environment, in our clothes, in our skincare products that are quite literally blocking or disrupting or interrupting the ability for our bodies to produce these hormones. So these are called endocrine disrupting chemicals. And 10, 20, 30, 40 years ago, we didn't see the same level of exposure to these chemicals in our day-to-day lives. Having a dataset that accounts for a modern woman, today's woman, and all of her exposures and her lifestyle factors is the most relevant data set there is. We can't rely on old inference data.

Jonathan: I think one of the things you've also been looking at is endometriosis, which I heard mentioned earlier, but I'd love for you to explain what it is as well as what you've discovered.

Helen: So endometriosis is a devastating condition that actually acts almost in a similar way to cancer. So it acts in a way whereby it can travel to other places in the body, starting typically in the uterus and parts of our highly receptive lining of our womb. If you think about it, it's almost the most receptive and susceptible to change environment there is because it can literally accommodate huge growth to expand and accommodate the growth of a fetus. But those cells can also undergo massive changes and are hugely receptive to our hormonal changes and when they migrate elsewhere. They tend to form almost lesions that can be inflamed and cause extreme, both cyclical and systemic pain, meaning cyclical being that it can be worse at a certain part of your menstrual cycle. And then systemic being it's all over your body. And this pain is as a result of these endometrial cells that migrate elsewhere in the body or remain within the uterus and they build up. And what we don't understand yet about endometriosis is really how do we treat it. But moreover, what are the things that are causing that to happen? There are a number of theories out there, but nothing that really actually lands true for everybody.

Federica: There's really interesting research looking at the role of the gut microbiome with endometriosis and dietary factors. So some of the research looking at early life exposures, for example, has identified that children and young women who are exposed to a very high red meat diet have a much increased risk of endometriosis in adulthood. And we do know that the gut microbiome plays a role in downregulating the inflammatory pathways that are very, very involved. And endometriosis really is an inflammatory disease, and gut health can help to downregulate this and bring it down. But it is a devastating condition and I think now we know more about it a little bit. There's more in the public sphere, but around one in 10 women suffer with endometriosis as well. So it's quite a high number of women.

Helen: I think one of the most devastating things about it is that women know there's something wrong with them. They seek help. Endlessly and don't receive help. And because of the role that it plays in terms of think about what's between our hips. There's a lot. There's a lot. There's our bowels, large small intestine. There's our uterus, our ovaries, our bladder. It's all crammed within this one space. And so when you have. Pain, for example, if that tissue is deeply infiltrating into your bowel, will you present with bowel like symptoms and you're sent down a very different route to traditional gynecology. And so what we've seen is that symptoms can be highly predictive of this pathology and that the time it takes to get somebody to a diagnosis is on average, nine years.

Jonathan: Nine years.

Helen: Nine years. It takes a woman on average because again, sometimes symptoms are quite insidious. We've also normalized pain in women. We say that you should tolerate it, expect it, and that that's just part of being a woman is getting monthly pain, but it should never be debilitating and crippling pain. And so we oftentimes tend to minimize menstrual pain. And so we either have to justify it or validate why we are feeling this and really scream for medical attention. So the time to diagnosis is actually one of the worst impacts about endometriosis. And so what we've seen from our data is that when you look at nearly a million health assessments and you look at the women who have a diagnosis of endometriosis, then we can blind everything else and we can say, what were the things that could have predicted endometriosis in this person? And one of the most powerful predictors is whether you have a painful poo. So, painful bowel movements is one of the most powerful predictors of endometriosis, and very often that is a question that is not asked of you if you are undergoing a gynecology examination that actually can be transformative in reducing a diagnosis time from what could be nine years for some to fewer than nine days.

Federica: Wow. So you are now able to diagnose endometriosis.

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Helen: You can never diagnose it in the absence of an investigation. You need to see the tissue. But what we can do is say with 98 to 99% confidence, both precision and recall, that we suspect you will have it. And therefore the first person you should go see is a gynecologist or an expert in endometriosis.

Federica: So you've reduced the wait time from 10 years to eight days.

Helen: Yeah.

Federica: That's amazing.

Helen: Yeah. And that really is the power of data and being able to collect data at this critical time point so that you have blood results, you have health assessment results. But moreover then we have scan results. So it enables us to really create this multimodal data set that enables us to interrogate different pathologies.

Federica: No, it really matters and it goes hand in hand with medicine, right? Both can be useful, but if we start by looking at the hormones that influence metabolic health and appetite, Jonathan. Inside our gut, about 1 to 2% of the cells are there just to make hormones. They're little hormone factories, and we have a dozen of different hormones including GLP-1, which is now made famous thanks to GLP-1 medications that's actually a hormone we produce in our gut ourselves from these amazing cells. My favorite are called the L cells. So if we feed these L cells properly, they will produce GLP-1 for us. They'll produce another peptide called PYY for us. And these hormones have a multitude of effects, not just on how hungry you feel, but how slowly your gut empties or whether your pancreas starts to secrete some pancreatic enzymes to digest fats. PYY especially travels to the brain and literally tells our brain to stop eating or to seek more food. They work together in harmony. Now, when we think about these enteroendocrine cells, they're called these little hormone cells in your gut. They're so important for conditions like PCOS, because if these L cells are happy, they can produce these hormones and they can help to regulate satiety and signaling for hormones like insulin, insulin resistance, which is created in the pancreas. Now, insulin resistance is one of the hallmarks of PCOS, for example. So when we think about our diet by nourishing our gut microbes, they produce short-chain fatty acids. They produce the food that these specialized cells in our gut thrive off. So if we can feed these cells well, they'll actually work for us. Now, I was talking about PCOS earlier. So amazing data shows that giving women with PCOS a high fiber diet, especially high in fermentable fibers such as inulin or beta-glucan, which is found in oats, for example, can actually improve insulin resistance as much as taking a pharmaceutical drug that does the same: Metformin. So it can be incredibly powerful, as powerful as the drugs. But Metformin doesn't really help with weight management, whereas the high fiber diet does even better than the drug. It's exciting to see that actually diet can play a fundamental role, but we have to feed our guts, the food it needs to maintain a very healthy system that can actually help these cells make the hormones for us.

Jonathan: I think what you're saying is in my gut, I have these L cells. Yeah. And that they're being fed basically by the output of these microbes inside my gut. And so I need to make sure that I'm feeding the microbes the food they need because they are then giving these outputs for these L cells. And these are then helping to manage a number of the hormonal imbalances that we've been talking about today with both of you, and that you're actually saying this is linked to, for example, being able to reduce symptoms of PCOS.

Federica: Yes, and the same with endometriosis. When we think about inflammation, again, if you feed your gut well, the gut microbes make the chemicals that are necessary to make sure that you have a really good gut barrier, which reduces the leakage of what's supposed to stay inside your gut to the outside. So, endotoxin leak. If you reduce that, then you are reducing inflammation. And we've seen in our research on menopause, very similar patterns where the gut microbiome, the estrobolome, so the microbes that are involved in estrogen regulation, they suffer if we don't feed them well.

Jonathan: Let's say I'm really wanting to make sure that I'm trying to maximize the output of these L cells because I'm worried about these hormones. What's the go-to? What are the key things?

Federica: What's the gourmet meal for L cells? So it is a lot of the principles that we know for gut health. Generally a variety of plants. So gut microbes each thrive on slightly different fibers and prebiotics from phytonutrients, for example, polyphenols. So we need to give our guts a wide range of foods, right? We have to give them several plants. 30 plants a week is a good starter. It's a good aim, we want to make sure that we're including plants that are also high in healthy fats. So Omega-3 fatty acids, the best sort of source is fish and seaweed, but also, we find a source of Omega-3 fatty acids in nuts and seeds as well. And actually those types of fats are really good for our gut microbes. Making sure that we introduce things like fermented foods, which can bring even more benefit from live microbes themselves, but also from the fermentation products of those microbes. So focus on adding those in more. And as I said, fermentable fibers are the ones that have been shown in clinical trials to really move the needle with PCOS. But they're all found in plants. So if you are having this really nice variety of plants, you'll be doing that. And to Helen's point earlier, micronutrients are really important for things like thyroid health. I mean, we haven't talked about zinc, for example, but zinc is essential for testosterone production. For example, if you're having nuts and seeds in your diet, you'll get zinc. You don't need to worry about taking a supplement for it.

Jonathan: And Federica. I just heard the word zinc and so I'm sure all our listeners were the same. It's oh, so zinc sounds really important.

Helen: When the sperm hits the egg, there's literally a flash of zinc.

Federica: It's amazing that you can see imaging of when it happens and flash, it's a firework.

Helen: Yeah.

Federica: And that's zinc. It's an essential mineral, but you need it in tiny quantities, but it has a very important role and zinc you can get from your nuts and seeds from your seafood. So if you're following a Mediterranean style diet, a diet that we propose in Zoe, all of our app is designed to give you this kind of diet, right? If you follow that advice, you will be getting all these essential micronutrients, all the fibers and the polyphenols that your gut thrives with.

Jonathan: I just want to clarify though, because I think a lot of people will be listening to this and saying, no, but this is really important for me. For example, my hormones are disrupted, or I'm worrying about making sure that I can have a baby. Surely I need to get a supplement because that feels something medical versus just relying on food.

Helen: I'm always led by food. When it comes to supplementing, I think you should supplement first with food, but I think you should never supplement in the absence of action without knowing what's wrong.

Federica: The only exception here, Jonathan, it's important for public health, is that if you are trying to conceive and you are actively trying to conceive or just find out you're pregnant, taking a folic acid supplementation is recommended. So you can go to your local pharmacy or even supermarket and pick up a folic acid supplementation. It's recommended for the first 12 weeks of pregnancy, and even before you try to conceive if possible.

Jonathan: Helen, what about fertility? I know that's a big area of focus for you, and I'd love to understand both what a woman can do to increase her chances of getting pregnant, but I understand that also there's research that there are things that men can do to increase chances of fertility.

Helen: Absolutely. I think we're finally starting to address that at that moment of fertilization. At that flash moment, the sperm is delivering 50% of the DNA that is contributing to the fetus. And so it is the 50 50 split in terms of what we are delivering from a DNA perspective. So the sperm plays a really fundamental role. I'll start with that because as I mentioned at the beginning, sperm have a three month lifecycle, and so in just three months making changes to your diet as a man can radically improve. All of the different parameters of sperm health. So there's an amazing study saying just a handful of walnuts every day increased every single parameter of sperm health, just from small dietary interventions, lifestyle changes.

Jonathan: Is there any other key actionable advice you would give if you're a man listening who wants to improve their sperm count?

Helen: Yes, you have a very minor role to play and yours is quite enjoyable, in fact when it comes to making a baby and so abstaining from smoking, drinking alcohol, all of these things for just three months prior to wanting that perfect swimmer to make it. It goes a long way. It doesn't go a long way just to contributing to a fertilization event. So we thought we can separate it out and say fertilization has occurred, the sperm has fertilized the egg. But actually it's more about what does that DNA contribute to? And we now know that the DNA, that the sperm contributes because the egg is the largest cell in the body and the sperm is the smallest cell in the body. It means that the role the DNA is playing is quite different. And the role the DNA, the sperm plays is actually informing the placenta. And so what we've now started to learn is that the health of the sperm can be what contributes and dictates whether that pregnancy will last, can be what contributes to miscarriage. And so when we flippantly now talk about miscarriage and it happens to one in four women and actually. We so often end up being victim to the blame or the self blame or the narrative that we have done something wrong. Actually, now we're starting to see that the sperm is playing a huge role in that healthy placenta.

Federica: Right. Yeah.

Jonathan: And can I just confirm what you're saying is the advice you're saying that abstaining from smoking and drinking for three months in advance, at least. Has a real impact. Massive impact on improving the sperm quality and therefore reducing risk of miscarriage,

Helen: Sperm quality, the risk of miscarriage, the overall health of the pregnancy. We are now starting to see studies that say sperm health is linked with whether you have morning sickness, but also the child's health. So one of the biggest studies that was done, the UCL looked at, it was called the healthy dad study, but internally the Fat Dad study. And what we were able to see with this was that pre-diabetic men who underwent bariatric surgery and then reversed their status, actually conferred that pre-diabetic state in the newborns. And so even though we like to think that our germ cells or sperm and our eggs are a clean slate. In terms of our health, actually, they carry the marks of DNA damage that we have had in our lives. And so that actually has a transgenerational impact on your children's health. So just three months seems nothing but it could be. It's the rest of your child's life.

Federica: And it's interesting because Jonathan, we think about the egg's health, which contributes to specific factors in the woman's health, but then paternal health contributes to different factors. So just as Helen said, the placenta's one of them, but the child is himself or herself. Mental health is often really closely linked to paternal health at conception. So we see that things like autism spectrum disorders are linked to paternal metabolic health at conception. These are all associations, but it's really interesting to see how important it is to think about paternal health, just the same way as maternal health. It takes two to tango. It is 50 50. About 50 to 60% of pregnancies aren't planned, so it's not possible for everybody. And it's not about guilt or blame because actually what we also know is that humans are very resilient. So you can have a perfectly healthy baby born even if you haven't done all the things beforehand. Right? So I think another really important thing for pregnancy is it's about having adequacy. So if you have adequate nutrition, you're in good health, you don't have to be in perfect health, then your body will do the rest. Pregnancy is very efficient. It will take what it needs from the mother and for the baby, right? It's not about. Oh my gosh. I had that one glass of wine, it's about what's the pattern? What's your overall pattern like? What are you consistently doing? Those are the things to think about. More consistency is king, and then the detail biology is pretty flexible, and our bodies are good at dealing with some challenges, especially if our consistent piece is strong.

Jonathan: So we've talked a lot about men and what they do that can affect fertility. What would your advice be to a woman who wants to increase her chances of getting pregnant?

Federica: The diet we've already talked about, Jonathan. So a very high nutrient density diet with plenty of vegetables and fruits, nuts and seeds, and oily fish three times a week, reducing alcohol intake. Stop smoking if you're smoking. Reducing behaviors like vaping or illicit drug use. So I remember reading one of your reports and seeing that about 9% of women who were actively trying to conceive were still taking illicit drugs. Those behaviors are going to impact fertility. Find out where you are on your fertility journey, how healthy are you and how your hormones behaving. And then you can eat and live a lifestyle that can support your fertility further.

Jonathan: Amazing. I'm gonna try and do a little wrap up. So my starting point is I'm now thinking about hormones like this orchestra inside my body, all these different hormones, way more than I realized I had. And if it's all working together, it's brilliant and it's helping me to deal with these horrible shocks, like suddenly seeing my ex across the room. But it is very possible, particularly it sounds like, in our modern western lifestyle that some of these hormones are not playing the right tune and then suddenly it's all going wrong and that there are some very common situations. We talked about PCOS, which I think you said affected 1 in 10 women, which is I think related to high levels of hormones like testosterone, and that has big impact, not just on your ability to have a baby, but your weight and your brain, all these sorts of things. But we also talked about endometriosis and just how devastating the pain is for women. And it takes nine years today for this to be identified. So that's really extraordinary. We talked about the thyroid, the most common problem you said that anyone has. Actually, you can just take iodine and it fixes it. So it seems so simple. And I remember this brilliant thing you said that, Helen, the further you are from the sea, the higher levels of thyroid deficiency. Yeah, we talked a little bit about men and talked about testosterone, and I think my big takeaway was if I'm injecting myself with testosterone, my testes are going to stop producing it, I'm gonna become infertile. So that seems like a pretty important thing to bear in mind before doing it because everyone else in the gym is doing it. And then the biggest thing I took away, I think was just how important the food is that we eat, on this. And I'm struck by it because it's outside really of what we often talk about on this podcast, but we understand it quite well. These mechanisms that there are, these specific L cells in our gut are creating all these hormones, but it only works if they're getting fed sort of the right chemicals from our microbiome. And this issue is that many of us are reaching a diet that is just basically not feeding those microbes what they need. And an example of this hormone you said is GLP-1. So if we're eating all the right food, then we probably don't need to inject ourselves with the GLP-1. But this is true for lots of other hormones. Yes. And what you said is there's some very clear advice. So eat a variety of plants. 30 a week because what you're trying to do is lots of different fibers and polyphenols to feed all of these different microbes. And you mentioned whole grains and legumes, but also big focus on healthy fats. So this is oily fish and nuts and seeds, fermented foods on top. And then interestingly, what you're trying to do is you're giving these microbes all of these different sort of fermentable fibers and micronutrients, but rather than think about that as a massive set of supplements that you're trying to eat, actually these are all found in plants because that's what the microbes are expecting. And if you're eating this diversity, then actually I shouldn't immediately be worrying about, like I need to take a zinc supplement. Actually, I'm getting this across this set of foods. Yeah. And then finally, I don't want to leave without talking about fertility. I had this wonderful moment where you just bonded over the flash of zinc. But interestingly, apparently, it takes three months to create sperm. So if I can completely reset the quality of my sperm within three months, but my diet is critical. And today, most men's sperm is 50% worse than I guess our grandparents', which is a bit depressing. Literally a handful of walnuts can increase the number of them and how well they swim, which gets your sign of sort of how bad it is. And so going to that same sort of diet that we were talking about before really makes a difference not just for women's fertility, but also for men's fertility. And that alongside that drinking and smoking have a big negative impact, both for sperm and for women trying to be fertile. So there's an enormous amount you can do within lifestyle that can really profoundly change your ability, not just to get pregnant, but to go on and successfully have a baby.

Helen: Yeah. One of my best students.