The Dr Louise Newson Podcast - 182 - Mental illness and the role of estradiol with psychiatrist Professor Jayashri Kulkarni

Episode Date: December 13, 2022

This episode contains reference to suicide Professor Jayashri Kulkarni is a psychiatrist working in Melbourne, Australia, specialising in women’s mental health and researching the role of estradiol in mental illnesses such as schizophrenia and depression. She founded and directs the Monash Alfred Psychiatry Research Centre, a large clinical research group in Melbourne.  In 2022, Professor Kulkarni launched and directs HER Centre Australia – a Monash University Centre delivering Health, Education and Research in women’s mental health - dedicated to improving the quality of care for women with mental illnesses by developing specific treatments tailored to suit women’s needs. In this episode, the experts discuss the different ways estradiol influences brain health and function, what this means for healthy brain aging and longevity, and they share some of their experiences when helping women with mental health changes during the perimenopause and menopause. Prof. Kulkarni’s tips for women experiencing mental health changes: Trust your instinct – you know you best. If you think it might be hormones, help is available. Look at your background history. If you had premenstrual mood changes or postnatal depression in the past, this may mean you are particularly sensitive to hormonal changes. Early life trauma (e.g. neglect or emotional/physical/sexual abuse) can disrupt hormone signals and brain chemistry and this may make you more vulnerable to mental illness. Whatever your past history, there is help available in the form of HRT. See your local healthcare provider or a menopause specialist if needed. You can find the Meno-D questionnaire here. This tool identifies the specific mood changes that are more typically present in perimenopause and menopause related depression. For more information on Professor Kulkarni’s work and research, visit www.maprc.org.au

Hello, I'm Dr Louise Newsome and welcome to my podcast. I'm a GP and menopause specialist and I run the Newsome Health Menopause and Wellbeing Centre here in Stratford-Bron-Avon. I'm also the founder of the Menopause charity and the menopause support app called Balance. On the podcast, I will be joined each week by an exciting guest to help provide evidence-based, information and advice about both the perimenopause and the menopause. So today I'm really, really excited actually to introduce to you someone called Professor Kolkani, who's the other side of the world, a long way away. And I've reached out to her a few years ago now to say,

I've read your work. You're the very, very inspirational and I'm really worried about the mental health aspect of the menopause. What do you think? And you replied to say, it's a huge amount of work and people often aren't listening, Louise, what can we do? And so we've sort of reached out a lot and I still hold you in such high esteem and regard and I'm very privileged that you're here today. So thank you very much. No, thank you very much for inviting me. So here I am in Melbourne. Everyone's going to bed and you're starting your day. So we do have the problems of being in different time zones, but we are absolutely, I feel like I've found a kindred spirit in terms of the work that we're doing. And I'm really appreciative of all the work that you do.

And I think we both realise the mountain that we have to move in order to get people to understand about the mental health aspects of menopause, because they're certainly not there yet, except for our patients who of course are unfortunately suffering because of this lack of recognition of the effect of menopause on the brain. Yeah, and so just to take it back, so you're not a gynaecologist, you're not a GP. What are you? I am a psychiatrist. And I've been a researcher pretty much from the time that I got my fellowship of the Royal Australian

New Zealand College of Psychiatry. and I've been in neuroendocrine work, and I first started doing research looking at the use of estrogen in women with schizophrenia and looking at the impact of eustradial in the brain for women who had psychosis. And it was really interesting work and pretty pleased that I got into the field, and we found that, in fact, eustradial was really good for decreasing some of the auditory hallucinations and really awful, awful symptoms that women with schizophrenia have. And learning more about the hormone side of things, then I expanded into looking at depression.

And obviously, menopause depression is a really important part, but many other aspects of women's mental health. Yeah, and it's so interesting, isn't it? So I think for many years, and I think about this a lot, actually, the menopause is defined by whether we have periods or not. So it's almost defined as to what our uterus, our womb is doing. And we know that our ovaries are attached either side to our womb. And so it's about whether our ovaries are working or not.

And then it's talked a lot about reproduction. And there's a sort of post-reproductive phase as in the menopause. So as a menopause or woman, I could be defined because I don't have periods. I could be defined because I'm not fertile. But actually what I as a scientist and the doctor, who's very holistic, thinks about, well, it's loss of hormones in our body that are really important biologically active hormones all around our body, but especially our brains. And I think that it's quite challenging, isn't it, for some people to realise. And I feel really bad. I didn't realise that 30 years ago when I was a junior doctor.

And when I did psychiatry, which I really enjoyed, it's just the. most fascinating specialty. No one talked about mental health and female hormones. And I don't think it's moved forward, has it, really much? Not really. Not really. It's still an issue. And somehow we've managed to get ourselves into the situation where the brain or, and I don't actually think there is a mind, I think it's all brain. We've made up the concept of mind to cover the feelings, emotions and cognition, but really it's brain. And somehow we've put a divide between the body and the brain. So, you know, psychiatrists will never think about the body or don't think about the body very much. And in particular, these hormones, estrogen, progesterone and testosterone have got

the label of being reproductive hormones. And it's like that's all they're there for is to help with reproduction. And of course, that's completely wrong. These are the really key and potent brain steroids, and they have enormous numbers of function in the brain. But yeah, we still operate in that Descartes philosophical dualism of mind and body being quite separate, which is really very archaic and neuroscientifically very wrong. Absolutely. And somebody wrote about Easterda being Nature's Psycho-protectant, which I thought was very interesting.

So talk me through then. Why are these hormones they're working in our brains? How do they work and where do they work in our brains? So estrogen, and first of all, you know, this is another thing that we do incorrectly. We talk about estrogen as if it's one thing and we talk about progesterone as if it's one thing and of course it's not. So we know even the natural estrogens, there's at least five different types and there are changes in the type of estrogen in pregnancy,

there's changes in the menopause. So, you know, this is a very interesting and complicated hormone. But when we look at what's going on in the brain, estradiol, which is 17 beta estradiol, is the most potent form of estrogen, does cross into the brain and has many receptors and, you know, sort of is the key to the lock in many different parts of the brain, as well as having an effect on all the brain chemicals that we know are involved in depression, anxiety, eating disorders, the whole works. So, you know, we all know about serotonin, as in the selective serotonin re-uptake inhibitors, the SSRI antidepressants. Estrogen has a potent effect on serotonin. It also has a potent effect on dopamine, which is the key neurochemical that's involved in psychosis or schizophrenia.

You know, there's many systems that estrogen has the chemistry interaction with. The other thing that is also happening is it's also having a direct effect. on the neural circuitry. So the actual wiring of the brain, both the hard and soft wiring of the brain, is influenced by estrogen in basically making circuits stronger. And how do we learn? We learn by repetition.

If I want to learn another language, I'm going to repeat words and phrases until it becomes ingrained or until that particular brain circuit is strong. And that's partly a role that estrogen has. It actually helps with new language. learning and also retaining knowledge. So that's all these things combined.

Estrogen has a chemical effect. It also has a structural effect. It also has a circuitry effect. That's why it's called the neuroprotectant or brain protection agent. And I think, you know, it takes it far away from ovulation and keeping the uterus happy and having a baby. You know, this is higher order memory, higher. order educational tasks, new learning, and also emotion and also clear thinking.

So it's got a lot of roles. And yet, for a long time, we just kind of relegated it to one bit of the body. And it's so important because, you know, all the things that you're saying, obviously without estrogen, there's no surprise that people find they can't concentrate. A lot of people tell me they've stopped reading books or listening to radio stations because they can't process the whole thinking through treacle, the brain fog, the reduced motivation, and obviously the low mood and all that that goes with it. And there's always a pushback at the minute.

There seems to be a big debate whether taking HRT reduces dementia or not. And if we flip it the other way, we know women who have low estrogen, as in who are menopausal, have an increased risk of dementia. That's very well established. And we know that the longer a woman is without her, her hormones, the higher the risk is. And I'm not saying that every men and impulsive woman will develop dementia. And I'm not saying that every men and palsal women will have mental health issues. And the brain is amazing the way it can adapt and use other hormones and other processes.

But because we have receptors for cells in our brains, they're there for a reason. The hormone is there for a beneficial reason, isn't it? So a lot of things, I think, when we struggle with in medicine, I just try and look at common sense and go back to basic pathophysiology. And so if you look at basic physiology, the way that estradiol is used in our brain, a very straightforward process is actually. Everybody now seems to know about serotonin, the so-called happy hormone, which is really important. And even dopamine, we talk a lot, even with addiction in the reward centres of our brains.

Of course we want to be happy. Of course we want to find pleasure and things. things that we do. But why are we stripping our body from Easter dial without giving it back? It doesn't make sense if you just look at our brains. I don't know whether there's, you can answer any of that. Well, I think some of the answers in that is that, you know, we've got to look at longevity. And if you went back to the Neanderthal ages, we wouldn't be around because, you know, people, women died in their 40s or even younger. So teleologically, our systems were not geared at that point

to actually keep going and going and going until the 80s and 90s, which is far more common these days. So we spend a lot of time as a post-menopausal woman, which none of our forebears did. And that's wonderful. You know, thank goodness we've got better infection control. We've got all the things that aid our long, longevity. And for a long time, medicine was all about mobility in people as we got older.

And it was about just making sure your bones were strong enough to support you. But what I think is really on the top of everyone's list is not just longevity, but fabulous quality of life. If you're going to live to 90-something, you want to be happy, you want to be productive, you want to enjoy what's out there. So it means that, you know, what, while we're busy supplementing this, that and the other thing to keep going with the aging process, I think brain aging as a result of menopause and the mental health aspects really need attention in a proportion of menopause of women. I never, like you, I'm not trying to put estrogen in the water supply here. I'm really, really keen that what we're saying is

some women, and unfortunately it's not a small number, but some women are really, really vulnerable and very sensitive to fluctuations in their estradiol levels in the brain. And when menopause hits, it's the biggest fluctuation that happens. And so these are the women from 45 years of age onwards who really experience maybe sometimes even first time ever major crushing, debilitating depression. Or if they've had depression before and it's been well contained and controlled, suddenly it goes haywire, and again, their lives become completely, you know, just distressed and despairing about things that they could do before. So I find, you know, they're the patients

I'm seeing, both groups, first time depression around 45 to 50, or a relapse of depression. And in both of those situations, the woman herself intuitively will tell me, I think it's my hormones, Doc, I really think something's happened to my hormones. And I sit there nodding going, yep, I agree with you. Many others wouldn't. No, and I think it's really interesting because for the last 20 years, we've always talked about the risks of taking HRT, which we know for many types, there aren't any risks or any risks are very low

with any type of HRT. But what we need to do is think about the risks of not taking it. So the risks not just too, like you say, our bones are hot, but our brains as well. So then because it becomes a bit more normalized in a conversation because there are a lot of people there who are not taking HRT because they feel it's a failure, or they have to have certain symptoms, or they can only take it if they have hot flushes because that's how it's licensed or whatever. Whereas it's these subtle changes that people won't attribute to the menopause.

And a patient I spoke to this morning was saying, oh, I feel fine. She said my work's become really stressful and my sleep's been a lot poorer. and we're getting some urinary symptoms, but I'm not sure that's my hormones. I think it's my stressful life. And I don't know. Of course it might be a stressful life. But I do know that we need to balance hormones because it's good for future health. And then we can see what's left.

And I didn't realize really until I open the clinic. And I suppose it's different here to general practice because people self-refer. So the women, like you're saying, the ones who think it's their hormones will come to my clinic. They won't come otherwise because I'm just a menopause and perimenopause clinic. But over the last seven years, I've seen massive pattern recognition of women coming and they're telling me that they think it's their hormones. But they're actually telling me very harrowing stories. I see and speak to a lot of women who are scared because they think they're going to harm

themselves or actually take their own lives. And I spoke to someone recently. And they do actually. They do. Absolutely do. We've had one lady who was on our waiting list, which thankfully we don't have a waiting this anymore but when we did her husband then reached out and said she doesn't need to come because she's taken her own life and her oh i spoke to the husband and she was on hrt actually

she was feeling fine she'd been on it two years as a 57 year old woman and her GP said you don't need it anymore you've been on it for far too long come off it and a few weeks after her mental state deteriorated and you know of course i don't know whether it's later to her hormones but we see so we hear a lot of people And to be honest, it's almost easier in the clinic because the women who we see who are very psychologically distressed have already been under psychiatrists for many years. They've often been sections. Quite a few have had ECT. Some of them have had very heavy duty drugs and then they're diagnosed with resistant depression. And I still, I say to them, I have no idea whether it's your hormones or not, but you're 57, your menopausal. I'm happy to try some hormones and see what happens, knowing they have full support from their psychiatrists and mental health teams and families as well, actually.

But it's often a combination I find of hormones, estrogenial, testosterone and if they need progesterone as well. But it seems to be this balance of hormones has the most amazing effect on women. And we also know that antidepressants can work better in the presence of estrogen as well, don't they? Yes, yes. For me, I feel I'm doing a very low-risk, no-harm medical approach. But it has been transformational in so many people's lives.

I feel, yes, it's great, but then it makes me even more frustrated, as you know, and I know you're frustrated, is that why are we not thinking more first-line of women who have postnatal depression when they're Easter Diles level, when they have PMS, when they're feeling bad just before their periods, when they're perimenopals or with these great fluctuations, You know, why are we not doing more about it? I find it really frustrating for women, actually. I think there's an incredible bias. And in the mental health area, you know, it's quite primitive, I've got to say. And this is one of the things we struggle with. We don't have objective markers of disease.

So, you know, the diagnosis of depression is dependent on the clinician making a good fist of it. Same with any of the mental health disorders. We don't have a biosepharm. And so then it becomes this kind of, well, you know, it's your guess, it's my guess, and we could maybe, you know, try this. And people are happy to experiment in the mental health field, which is bizarre, because I see women like you, you know, who've come with, they're on lithium, which is toxic to the thyroid and kidneys and blood, you know, it's got millions of side effects. And yet the doctors are very happy to play with lithium that's throw in an antipsychotic. you know that these are the nuclear weapons in the psychiatric armamentarium. So, you know, these are big drugs. And yet there's this kind of complete blank when it comes to hormone treatments,

which actually are easier to start and stop because, you know, I tell my patients, if it's not suiting, then you can stop and nothing dreadful is going to happen. Absolutely. And that's what's so important, you know, I always say to women, it's completely reversed. I'm not giving you an injection that's going to last for years or an operation. It is just almost that you're in control of every day. So you can try and see. And, you know, you can easily stop them, but also the dose might need changing.

And it's about optimising dose, I think, is also really important. Because a lot of women we see say, well, I've been on HRT and it didn't help. And then when you ask them what it was, the dose was very low. Or they weren't given testosterone. Or they only tried it for three or four days. and then they, you know, decided to stop, whatever. So I think it's really important that women have a good therapeutic trial, if you see what I mean. But the other thing is, is that a lot of these drugs, so ones such as ketiapine, you know, these heavy-duty

anti-psychotic drugs, a lot of psychiatrists in the UK, but probably for you as well, will measure prolactin levels because they can affect the levels of prolactin in the body. Now, when we have raised prolactin, it will suppress our follicular stimulating hormone or FSA, level, if that level is low, then we'll produce less hormones. So it's almost giving people a chemical menopause. So if they were having periods beforehand, but no one seems to be thinking about that. And a lot of these women who are on these various drugs find that they put on weight, they have raised blood pressure, they become slower in their mood, their cholesterol raises. And I'm sure that a lot of that's related to their sex hormones being so low. But it's almost

like that sort of area of all the endocrine pathways is forgotten, isn't it? Yes, absolutely. So I can't quite understand it. Well, I think it's the compartmentalisation that, you know, it's fine if you're a psychiatrist to work in the mental health field so you will prescribe the mental health drugs. But these drugs, the hormones, are in somebody else's bag, but somebody else is usually a gynaecologist or an endocrinologist, and they're not thinking mental health at all. So it's this very odd compartmentalization.

Yes, it's just, it's bizarre. It's the Descartes. You know, I always remember the mind-body split. And it's a really weird way to practice medicine because, in fact, the woman is a whole woman sitting in front of you with all the mind, the brain, body, and environment, all in interaction all the time. So I do despair of the compact mentalization that goes on. I hope that we've got generations of doctors coming through, the younger generations,

that are a bit more happy to, you know, have a bit of this and a bit of that and sort of look at the different fields, because we should be learning a lot more about what's the latest. What's the latest in neurology that I can apply in psychiatry and vice versa? And that's just two fields. But, you know, a lot of different areas, we need to get together and actually be able to look at the problems for the whole woman to be able to help her. And menopause is, somebody once said to me, menopause is the kind of nobody owns menopause.

It's sort of an orphan. It's left out there and it's ugly because it's middle-aged women. Who wants to know anything about middle-aged women? And no particular specialty owns it. So you find that, in fact, there's not a lot of champions. You know, you get advocacy for a particular blood disorder by the hematologists who go in marching in there. but who's marching for menopause? And I think we're really, it's a real problem.

You're absolutely right. I was talking to someone called Professor Chris Hardy this morning, who's from Newcastle, he's an amazing researcher, but he's a urologist, and we're doing some work looking at how hormones can reduce urinary tract infections and reduce the need for antibiotic prescribing. And I was talking about research, and he was talking about gynecologist.

And I was saying, hang on, Chris, it's not a gynecological specialty. who's going, well, what do you mean? I said, it's a women's health specialty, but then women's health is always thought of as gynecology. I said, but I need to research with somebody who's in general practice, who's in primary care, who's in medicine. You know, this is not about, I mean, I'm, I'm not a gynecologist. I think so much more beyond the pelvic organs. And I think this is where you're right, menopause has just drifted around. I said to him, look, if I was doing research in diabetes, I wouldn't get in touch with a pancreatic surgeon. He said, no, of course you wouldn't.

And I said, well, this is the same. And there are a lot of gynecologists who don't want to be involved in the menopause because they're doing cancer surgery. They're doing other work on the womb, very appropriate work, but not about a time in a woman's life when their gynecological organs are not working. Like, why would they go and see a gynecologist? And I think this is where we've got it wrong, actually. Yes.

That we really need to have a very joined-up. holistic approach because hormones are really important. Of course they are. But also, you know, what we eat will affect the way that our brain works. Even if I see a lot of women who have really itchy dry skin, actually, if you're driven to distraction with your dry itchy skin, that's going to affect your mental health, isn't it? Of course. I've had women come in and say they've given themselves lice treatment for their itchy head. And, you know, they've been to the chemist and spent a fortune and have this dreadful, smelly stuff in their hair the whole time. And of course, it's not helping.

It's just their hormones. Yes. I mean, we can laugh about some of the symptoms, but it underlines the point that it's a whole body phenomenon. So I actually look forward to the day when you have done this in the UK. We haven't here so much, but to actually have menopause experts who set up holistic clinics so that women can go and get their treatment and have the whole range of everything looked at because it does affect so many things. I mean autoimmune situations, the musculoskeletal

changes which then prevent women from exercising, which then means they gain weight, etc., etc. It's an awful holistic mess if it's not picked up quickly. Totally right. And, you know, I sort of, you know, we're talking not about the menopause, but it's the perimenopause, isn't it? That's really important. And one of the things that we're trying to work out with, as you know, we're funding a PhD student from Liverpool. And we're looking at this Mennode questionnaire that you have created,

which is trying to tease out how do we distinguish between clinical depression and perimenopausal or menopausal depression or hormonal? And it's very difficult, isn't it? But tell me about the MNOD questionnaire, just briefly, if you don't mind. The Mnod questionnaire, is pretty much based on the symptoms that I was seeing with a slightly different quality of the depression in that irritability, hostility, rage as the first emotional responses, was often what I was seeing rather than the classic sad, crying, take to bed kind of depression.

I mean, certainly we know that menopausal women can also have bouts of sadness and crying and taking to bed. But the rage and anger was really apparent. The fluctuation was the other side of it too, because often, you know, we'd have women present who were really feeling dreadful, feeling angry, their families had had it, you know, it was all going pear-shaped, and then all of a sudden they'd come good. And then it led to this kind of invalidation of them, because people would say, well, how come you're functioning so well this week and last week you were a disaster. And this is kind of the invalidation of the woman as well. Or worse, she would be diagnosed as having bipolar disorder, and it's specifically bipolar type two. And then out would come all the

nuclear weaponry of psychiatric drugs, and it was just awful. So I thought we need to get some pseudo-objective way to try and point out that there are different symptoms. And so I incorporated the rage, the anger, also the body symptoms, which does include hot flushes down the track, but, you know, starts off with the tiredness, the brain weariness, the body weariness, those sorts of more softer symptoms that you probably wouldn't pick up in the usual depression, major depressive disorder. My biggest point with the men O.D. is in the title, it's menopausal depression, because I wanted to get that out there to just say, even if you don't do much else, just recognize that there is an entity that is menopausal depression.

And it's going to, once you recognize that this has got a different causality, hopefully as a clinician, you'll realize there are different possible treatments that you can use. So, look, it's by no means a perfect scale. It's got lots of difficulties in the sense of, you know, we did quite a bit of validation work on it. But sure, it's not the be-all and end-all. But I like the title just because it hits people between, the eyes, this is different.

I think it's a real start. And I think often when I'm training and talking to other people, it's about involving the women as well. And so many women, if I say to them, do you think this could be related to your hormones? They'll say, oh my God, yeah, I'm not depressed. But at three in the morning, I think about how I'm going to end my life. Or just before I have my periods is where I plan what I'm going to do to really harm

or kill myself. But I don't want to be it like that other times. And they're quite clearly saying, and also I see a lot of, lot of women who tell me all this, but they've got a lot of insight into it, whereas I've seen a lot of people in the past who have really severe clinical depression, they have no insight. They don't care whether they're going to jump off a cliff or not, whereas these women really don't want to do it. And it's very subtle.

And I think this is where we need to involve, we need to involve our patients with everything that we do. But I think listening to them when they have mental health issues and often when they're saying, well, I felt like this after I gave birth to my first, second, third child. I felt like this before my periods when I was a teenager or in my 20s. I feel it could be related. Then I think we owe it to our patients, don't we, to think about hormones as well. When we know hormones are so safe as well.

And, you know, I spoke to someone who runs a ketamine clinic recently. He's a professor of psychiatry. And I said to him, why don't you screen women for perimenopals or menopoles before prescribing ketamine for them? he said, oh, Louise, I'm too scared to prescribe HRT. I'm like, oh my goodness, I would be far too scared to draw up a prescription for ketamine. So there's this sort of area where people are scared, whereas we have to change it. And I think for new generations of doctors, there are a lot more open-minded maybe.

And we need to just keep the narrative going because it will improve the future mental health of women without a shadow of a doubt, weren't it? Yeah, absolutely. Couldn't agree more. I think it's, I often wonder, where did that I'm scared of the hormone come from? Was it the women's health initiative in the 2000, 2001? But I'm not sure. You know, I think even before that there was a reluctance.

And then it just, of course, you know, became really the reluctance set in. And it's still worrying that, you know, I still catch up with patients who say, oh, my GP, my primary health care doctor will not prescribe HRT. because they believe that everybody who gets HRT gets breast cancer. And I go, well, that's completely nonsense. Yes. But where does it come from? Well, it's really hard.

And I've often phoned and spoken to different doctors who have refused HRT for their patients and their women who I've been really worried about their mental health. And they're saying, well, there's a risk of breast cancer. Well, actually, there's a risk of death in these ladies. And if they do jump off a cliff or do whatever, their risk of death is 100%. So let them decide, actually.

And I think this is where we have to use a lot of common sense as well. So, but there's, there's a huge amount we need to do. And it's been really enlightening talking to you. And I hope this will let people just think a bit more about the mental health. We've got resources on the balance hypermenopause.com website on the balance app. We'll share a link to the MNode questionnaire as well. And I'm hoping that we can do so, even though we're very far away from each other, that we can do some more joined up work with this and really take it.

it forward to help future generations. So before we finish though, I'm just going to pick on the spot. I always ask for three take home tips. And so I'm just really, really keen to learn from you three ways. If women have been listening or relatives or partners or friends of people who they think are struggling with their mental health possibly due to their menopause, you know, they're listening going, that's me. What are the three things that you would say to women who are thinking about their mental health symptoms being related to their hormones? First of all, I would say, trust your instinct because you don't get to be a 45-year-old woman and not know a thing or two.

So I would say, trust your instinct because you know you, you live with you. So if you are having up and down variations in your mood, that there's nothing particularly going wrong in your world, then you're right that there is something that needs hormonal attention. That's number one. Number two is look at your background history. If you were that woman who did get pre-menstrual depression or had a terrible postnatal depression or something postnatally in a mental health sector, then that's the second thing. That's a clue that you must take notice because you are more sensitive to your hormonal

fluctuation. So that's point number two. Point number three is a little bit more tricky, but I have found that some women who have early life trauma, and I define early life trauma as emotional neglect, emotional abuse, physical abuse, and of course sexual abuse, in their background story, that that tends to screw up the hormonal signals and the neurochemistry. So that is another group who are more vulnerable. And if you have that background, then you're more vulnerable. But in all three points, that vulnerability can be helped. So my fourth point would be go and see Louise Newsom's

clinic if you're in the UK. We'll try and see who can help you in Australia. But you know, you can safely try HRT or HT as it's called hormone therapy. If you don't like it, you can stop it. If you like it, it helps you then that's great. But it's just another treatment and we shouldn't be scared of it. Great advice. So thank you ever so much for your time, especially so late at night. Pleasure. And I look forward to speaking to you again. So thanks very much. Thank you for chatting to me. For more information about the perimenopause and menopause, please visit my website, balance, menopause.com or you can download the free balance app which is available to download from the App Store or from Google Play.