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REPLAY: Menopause: Oestrogen and the Brain with Emma Sutherland and Dr Nicola Gates

 
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REPLAY: Menopause: Oestrogen and the Brain with Emma Sutherland and Dr Nicola Gates

Dr. Nicola Gates, clinical neuropsychologist, researcher, and author, joins us in our podcast replay to discuss the important role of oestrogen throughout the lifespan, shining a spotlight on the menopausal transition. 

Commonly known for the vasomotor symptoms including hot flushes, insomnia, and weight gain, Nicola expands on the role of oestrogen in menopause making the connection between fluctuating oestrogen levels and cognition, memory, and mood changes. 

While menopause is a period of great change, Nicola and Emma address the influence of societal expectations and perspectives on the individual, adding to the mental health burden associated with the physiological changes of menopause. 

We hear of the different forms of oestrogen and their associated life stages and of the key role oestrogen plays in brain function. To support you clinically, Nicola provides us with some excellent clinical strategies to support the menopausal patient. 

Covered in this episode

[00:39] Welcoming Dr Nicola Gates
[02:22] Nicola’s menopause story
[03:32] Reframing menopause
[06:11] Roles of the different types of oestrogens
[07:33] Oestrogen and brain function
[13:21] Oestrogen and memory
[17:58] The brain produces oestrogen
[19:13] Differentiating between cognitive decline and menopause-related brain symptoms
[24:05] When to use hormonal replacement therapies
[27:56] Oestrogen levels throughout the menstrual cycle
[34:46] Oestrogen and depression
[37:51] How long until the brain adjusts to lower levels of oestrogen?
[39:11] Supporting women going through the menopausal transition
[45:13] Thanking Nicola and final remarks


Key takeaways 

  • Sex hormone fluctuation during menopause is associated with menopausal symptoms including hot flushes, night sweats, insomnia, weight gain and vaginal dryness. These sex hormones are also associated with mood swings, brain fog and poor memory during menopause. 
  • Menopause should be viewed as a celebration of health and a fertile life, rather than the Western view of menopause as the onset of ageing and decline. Attitudes towards menopause can influence the menopausal experience of the individual. 
  • There are three types of oestrogen - oestradiol, oestrone and oestrogen - each play an important role at different stages of the lifespan. 
  • Oestrogen is recognised as a neurohormone and is involved in oxygen metabolism within the brain in both males and females. Oestrogen is also involved in neurotransmitter function, with multiple oestrogen receptors present in the brain and the brain is able to produce oestradiol.  
  • Oestrogen receptors in the prefrontal cortex are associated with decision making, action selection, motor function, cognitive and memory function, emotional and motivational response. 
  • The reduction in oestrogen associated with menopause leads to reduced acetylcholine, involved in hippocampi function and memory formation, resulting in slow memory retrieval. 
  • Oestrogen and progesterone are psycho-protective neurohormones that support a person’s psychological wellbeing by reducing cortisol and the sympathetic nervous system response. Menopause can increase the stress response and impact mental health with reductions in serotonin, oxytocin and endorphins, increasing the risk of anxiety and depression. 

Research discussed in this episode

Study: Estrogens and Cognition: Friends or Foes? (Korol & Pisani, 2015)
Study: Cognitive function in association with sex hormones in postmenopausal women (Kocoska-Maras, et al., 2013)
Study: Changes in Brain Size during the Menstrual Cycle (Hagemann, et al., 2011)

Additional resources and further reading

Dr. Nicola Gates

Dr. Nicola Gates
The Feel Good Guide to Menopause by Dr. Nicola Gates
A Brain for Life by Dr. Nicola Gates
Research: ‘The Low down on Menopause’ Dr Nicola Gates, LSJ, 2015
Article: ‘Moving keeps you cool through menopause’ Psychology Today, 2020
Article: ‘Why does looking on the bright side work?’ Psychology Today, 2020

Menopause

Research: ‘Menopause transition: Physiology and symptoms’, Best Practice and Research Clinical Obstetrics and gynaecology, 2022

Oestrogen, memory and menopause 

Research: ‘Estradiol selectively regulates metabolic substrates across memory systems in models of menopause’ 2020, Climacteric 
Research: ‘Menopause and Brain Health: Hormonal Changes are only part of the story’, Frontiers in Neuropsychology, 2020
Research: ‘A research primer for studies of cognitive changes across the menopause transition’, Climacteric, 2020
Research: ‘Impact of menopause on brain functions’ Post Menopausal diseases and disorders, 2019
Article: ‘Menopause brain: The inability to think clearly is not ‘all in your mind’’, The Guardian, 2021
Article: ‘Brain fog during menopause is real - it can disrupt women’s work and spark dementia fears’, The Conversation, 2021
Article: ‘The fog of menopause’ Jean Hailes, 2021
Research: ‘Cognition and mental health in menopause: A review’, Best Practice and Research Clinical Obstetrics and Gynaecology, 2021

Menopause and inflammation

Research: ‘The peri-menopause in a woman’s life: a systemic inflammatory phase that enables later neurodegenerative disease’ Journal of Neuroinflammation, 2020

Management of Menopause

Research: ‘A practical nutritional guide for the management of sleep disturbances in menopause’ International Journal of Food Sciences and Nutrition, 2020
Article: ‘Menopause management’, Australasian Menopause Society, 2021
Fact Sheet: ‘Complementary medicine options for menopausal symptoms’
Article: ‘Managing menopause’, The Women’s: The Royal Women’s Hospital
Research: ‘Making choices at menopause’, Australian Journal of General Practice, 2019
Clinical Guidance: ‘Managing menopausal symptoms’, The Royal Australian and New Zealand College of Obstetricians and Gynaecologists, 2020
Article: ‘Menopause: Turning down the heat’. FX Medicine Magazine, 2010

Transcript

Emma: Hi, and welcome to FX Medicine, where we bring you the latest in evidence-based, integrative, functional and complementary medicine. I'm Emma Sutherland and joining us on the line today is Dr. Nicola Gates, a clinical neuropsychologist, researcher, and author. 

Today we're going to be discussing how menopause can affect our brain, our emotions, and our overall health. Thanks for joining us today, Nicola. How are you?

Nicola: Great, and thanks for the invitation.

Emma: My pleasure. Now, Nicola, you have written two books that are filled with research, case studies, and women's insights and I really love them both and I frequently recommend them to my patients. One is on the topic of brain health, and the other is on the topic of menopause. So, I feel you really are perfectly placed to help us navigate this topic today.

Nicola: Thank you. And you know I wrote the book on menopause because when I was writing the one on brain health and dementia, my friends all said to me, "Forget that. Tell us about our menopause brain fog." So, the second book was a natural segue from the first.

Emma: Yeah. It makes complete sense. And we know that menopause can be a rollercoaster ride. The sex hormone levels are dropping and changing, and results in symptoms that we commonly associate with menopause, things like hot flushes, night sweats, weight gain, vaginal dryness, and sleep issues. 

But what a lot of women don't realise is that these same sex hormones and particularly oestrogen, play a huge role in our brains and our cognitive function as well. So, they might be experiencing the mood swings, like you mentioned, and the brain fog and forgetfulness, in addition to those other symptoms. 

But actually, before we deep dive into this, what I think is a fascinating topic, I actually wanted to ask you quite a personal question. Now, I read in your book that you had a horrendous ride with menopause. Are you happy to share with us your personal experience on this?

Nicola: Yeah. Thanks for checking in with me. Yeah, I actually started writing the book on menopause before my own menopause began. I had a medical menopause. So, this life is random and joyous. And I was diagnosed with grade-three invasive hormone-driven cancer. So, I always joke that I'm an overachiever. So, I had two oestrogen-driven cancers. Sorry, one of them was oestrogen and progesterone-driven breast cancer and oestrogen-driven breast cancer. 

And I didn't tolerate the anti-cancer medications very well after a double mastectomy. So, they said, "Yep, let's whip out those ovaries. And guess what? Tomorrow you're going to wake up and be in menopause." And I tell you what, I was having about 3 to 4 hot flashes every hour, 24/7 for the first year.

Emma: That's just absolutely awful. And I think the medical menopause, I mean, that's an instant menopause when the ovaries are removed. And I can imagine that that's a bit like slamming into a brick wall because there's no time for adjustment like there might be in regular menopause.

Nicola: That's right. There is no adjustment. So, every part of the body that receives oestrogen, which let's face it, is basically the entire body, wakes up in a big shock. But the alternative to menopause is potentially death. 

And the other thing that I guess I really want to stress, I have had some flack about my book that's really positive and optimistic and called “the feel-good guide,” is that menopause is a celebration of health and life because if you're infertile or you have health problems, you've not been fertile, whether you have kids or not is irrelevant. Menopause means you've been healthy. And if you don't have menopause, it means you've either died young or you've had health problems. 

And every woman in the world goes through menopause, but only some women just conceive of menopause as this horrible problem. And I guess that's one of the first things I would invite clinicians in particular because I had doctors, my own doctor kind of said, "Oh, gosh. Menopause, it's going to ruin you." I think that's a really unhelpful attitude. Menopause, I really think we need to change the dialogue around menopause because the research shows that if you expect a bad menopause, you're going to get a bad menopause. And whenever I'm feeling a bit low because I had five hot flashes last night and woke up five times, the alternative is menopause is great. The alternative is death.

Emma: Yeah. And I really love that reframe because I think in the Western world, in particular, we tend to demonise menopause and look at it as a negative thing when in many cultures around the world and particularly traditionally celebrated that time in a woman's life. So I think this is a really great reminder to all of us to maybe rethink and reframe that menopausal time.

Nicola: Absolutely. I think the reframe is really important. And particularly when you start thinking about women's mental health, and during this time, this complex time in their life, we need to reframe it as a, “Yes, it's got its challenges. Inherently, it does. But let's think of it as a celebration and a reawakening. It's not a medical problem. It's not a pathology. It's a wonderful thing of life.”

Emma: Yeah, amazing. Now, let's just hit the basics for a minute. So, can you explain the different types of oestrogen and the role of each one?

Nicola: Yeah. And you know what? I think this is a good place to start for clinicians. I've spoken to lots of women putting my book together. And most women had no idea that there were different types of oestrogen. And I think this is part of the reassuring message that they need to hear, that you have oestrogen as a child, boys and girls both have a bit of oestrogen. Then we have oestrogen to help us go through our reproductive years. And then we go back, if you like, to E2...back to E1, sorry, post-menopause. So, let's talk about them. 

So, you have oestrone, which is E1, which is post-menopause. And that's largely produced by fatty tissue. So, that's converted. So, that's important to be at healthy weight. E2, oestradiol, is produced in the ovaries. And that's the one that's active for the psychological and body function and brain to get us through our fertility years. So, to help convert us, we go through...it takes years to go through puberty to get up to this full reproductive life, and then takes years to go down to when you don't have the E2 again. And the last form of oestrogen is the one you only get when you're pregnant. And that's just to support pregnancy, but not have, obviously, ovulation and be fertile.

Emma: Right. Great explanation.

Nicola: Oestrone.

Emma: Yeah. And I've often heard that menopause is kind of commonly called the “second puberty” because, I guess, those hormone levels are adjusting again as well. But how does oestrogen actually affect brain function? So, as clinicians, I think most of us look more on the physical. We understand hot flushes and the mechanism there. But what about the brain function side of things because this is where I want to focus today?

Nicola: Yeah. And I guess there's got to be a caveat somewhere in this interview. And there's two caveats, actually. One is that we don't really know a lot of the workings of oestrogen, so that makes it really, really exciting. And what we chat about today will be improved upon and knowledge will be expanded considerably. And one of the reasons is that women and even female rodents in biological models and things weren't included in research. So, everything we're talking about is really for the last 20 to 25 years. So, that's the first thing. So, there's a lot of information coming out all the time. Now it's a really exciting area of research. 

So, the understanding of oestrogen in the brain has been exceedingly limited. But oestrogen is now recognised as a neurohormone in the workings of the brain. So, yes, it doesn't just change the body fertility. So, there's research that suggests that's involved in oxygen metabolism. And again, I've got to say, so men have oestrogen in their brains. And we have oestrogen in our brains. Oestrogen is important in the brain of both... When I talk about male and female, I'm talking about biological sex.

Emma: Yeah.

Nicola: I'll just put that out there. So, the men and women, males and females have oxygen... Sorry. They have oxygen in their brain, but they have oestrogen running around in their brain. And it is believed it's used in oxygen metabolism.

Emma: Okay.

Nicola: It's linked to multiple neurotransmitter functions, so including the mood-regulating chemicals that we've already talked about, including serotonin and endorphins and oxytocin. It also has an important role in memory. And the reason I started with the caveat is because there's new research coming out all the time. 

And for example, we now know that there are different… So, there's not just one oestrogen receptor. We also now know that there are multiple oestrogen receptors in the brain. And I think that's really important to say that our knowledge is constantly expanding. 

In terms of the sights of the brain, so they...sorry, receptors. There seems to be receptors in the cytoplasm in cell membranes and nuclei. So, as I said, there's different... This is where it starts getting complicated. There are multiple oestrogen receptors, number one. There are different places where those receptors are located.

And it's now been discovered that... So, for example, Korol's work in 2015. They found that there were oestrogen receptors widely distributed throughout the brain, but significantly in the prefrontal cortex. So, that's involved in higher-order functions in the dorsal striatum, which has a role in decision-making, in action selection, initiation in cycles because it's important in integrating sense and motor information with cognitive function and emotional or motivational information in the nucleus accumbens, and so that's like a neural interface between emotion, motivation, and action. So, that's really involved in reward. And when you think of reward, you're going to think of sex, food, drugs, sleep regulation. So, those are sort of four basic functions. And also now what we understand, it's got a big role in the hippocampus and memory formation.
Now, I think we're going to touch on all of those further down. But there's other things as well. So, I mentioned in serotonin, that sort of monoamine neurotransmitters. It's also going to involve a role in neurogenesis, so the development of new brain cells. It seems to have a role in inflammatory processes, neurological, as well as in simple cognition and emotional function. 

I could keep going, but where I'm going now, I guess... So, some of this research has now got a good 10 years behind it. Some of the research I'm talking about has undergone less review and less repeat, but there's also a suggestion now that oestrogen receptors may have a role in regulating the brain's hemispheres. And we know that, for example, women's brains and male brains sort of operate a bit differently in terms of hemisphere influence. And oestrogen might involve inhibiting some other dominant hemisphere. And that actually can become important later on when we talk about emotions just because of the mental health issues that women present more than men.

Emma: Yeah. And I definitely want to cover that because it's something that, as clinicians, we see this in clinical practice and I think this is really important to sort of dive into that as well. It's just so complex, isn't it? 
I mean, I can barely wrap my brain around all of that. And I think it's quite astounding and exciting that the research is really evolving, as we speak, and it's so important for us to try and stay updated with it and what it might actually mean. So, I love the fact that you can translate that complex research for us into these clinical-based pearls that we're going to get through today. 

But why do you think memory processing and learning is so impacted by menopause? Because we do see this clinically. Women are forgetful or they're having trouble remembering things. But what is it about the changes in hormones that impacts the memory processing and learning?

Nicola: Yes. And I guess, as an aside, not so much for menopause, but one of the other things, the time that women report forgetfulness is when they're pregnant. And we talked about the special oestrogen to support pregnancy. So, the understanding is that one of the reasons memory formation gets upset during pregnancy is that there's rewiring going on in the brain. And it's not so much that they are forgetting so much as it’s just more effort to do memory retrieval. And that's because they're setting up to be better at multitasking, which, as you know, is not actually...it doesn't exist. What's actually happening is we toggle faster and faster. So, women that have had a pregnancy are better at toggling between different focuses - foci, I guess it would be - different foci of attention.

Emma: Yeah.

Nicola: So, the other thing that... So, in terms of menopause, so there's research that shows that during menses, the brain has to insulate itself against the swings of oestrogen that occur in the menstrual cycle. And that's as a buffer so the brain can keep functioning exactly the same no matter where we are in a menstrual cycle. 

During menopause, obviously, we're getting less oestrogen. And again, the brain has to buffer. But essentially, I mentioned before about the hippocampi, so there's two, one on the left, one on the right. And they're all at the central memory formation. They don't actually hold the memories and memories are distributed throughout the cortex. The hippocampi have a role in memory formation because you've got to remember that to store information, there's got to be cellular changes and the hippocampus is crucial in the memory formation, the cellular changes. 

Now, oestrogen increases the enzyme that's needed to synthesise acetylcholine, which is crucial in spines and the hippocampi that are involved in memory formation. So, the less acetylcholine you have, the less spines you have in the memory structures, which are used for communication and less information transfer into memory.

Emma: Right. So, does that mean that a woman has trouble making the memory in the first place or that she has problems retrieving that memory? Or is it a bit of both?

Nicola: A really good question. They talk about it in information transfer, so less memory. And when they look at rodent studies, female rodents, obviously. And we didn't have to look at female rodents in memory studies up until very recently, so we didn't know this stuff. So, it's all exciting and new. What they found it was memory formation and retrieval. So, they learnt things and then they couldn't access the information that they already acquired. So, certainly, rodent information would suggest that there's an impact on retrieval and, importantly, formation.

Emma: Yeah. And I find that fascinating because I would assume that it's problems forming the memory in the first place, but it's more that it's trouble retrieving it. So, I think this is a really nice thing to share with women when they're sitting in front of you and they're feeling like they've got some age-related cognitive decline, to explain to them, "You are actually forming those memories. It's the change in oestrogen causing a change in the enzyme that helps you retrieve that memory." Yeah. Fascinating stuff.

Nicola: That's right. So, the less spines... When you're making a memory, the more spine - and spines is the neurological term - but think of it as a piece of information, and the more hooks you have on that information, the easier it is to find them because when you're trying to grab something, the more hooks on it, the easier it is to pick it up. Right? And that's the problem.

Emma: And I mean, the brain actually produces oestrogen, which is something that I didn't know until I read your book. So, tell us a little bit about that. Where is it produced? What type is produced?

Nicola: Okay. So, as I mentioned earlier on, the brain needs to insulate itself against these changes. And initially, they used to think that the brain used to just hook up systemic oestrogen, oestrogen that's already floating around in the body. They've now realised... And again, there’s caveats. This is very recent research.

Emma: Okay.

Nicola: The understanding is that the brain does make E2, oestradiol, at the hypothalamus. Okay? And they've looked at, so, for example, rhesus monkeys and they've done studies like that. And this is why men convert testostrone into oestradiol for the same reason. Your brain likes it. And if your brain thinks it hasn't got enough and it needs to get a buffer, it will convert at the hypothalamus.

Emma: Right. I actually never knew that, so it's great to be able to kind of expand my mind itself on this. 

And one of the things I did want to talk about is some white flags, or maybe some differentiations between that age-related cognitive decline and the menopause-related brain changes. Because I'm really thinking about the 55-year-old woman who came in to see me and she's got brain fog and weight gain and she's actually very worried that she has early dementia, and she says she's got trouble getting her words out, she can't remember where she put her keys. I mean, that's a frightening situation for a woman to be in. But what are some white flags that we could keep front of mind when we're working with women like this?

Nicola: Yeah. Good question. And this is obviously why I wrote my book for my friends saying, "Nicola, help us, help us." 

Okay. So, let's just step back a little second with the question. So, dementia or neurocognitive disorder, as it's now termed, the most common form is Alzheimer's disease, and that counts for about 70% of all cases. Now, the neuropathology of Alzheimer's disease is plaques and tangles, which is not what's going on in menopause. Okay? So, I guess that's the first thing to say to people is that dementia, Alzheimer's disease, it's a neuropathology logical condition. It's got these problems in the brain. And that's nothing like what's going on in menopause when the brain is adjusting to having less oestrogen.

So, there are plenty of reasons why people forget things. And so there's a slowing down of memory retrieval in menopause, but there's also a lot of other things going on as well. And people often feel that they're forgetful, for example, when they're stressed, or they're unhappy, or they've got too much going on in their life. And that can make people forgetful. And because of the amount of information, people often misattribute what's going on to something terrible, and we know this because our emotions and memories sit side by side. 

So, if someone's worried about something and really stressed, we tend to think of things that are worse rather than better. So, when people are getting forgetful, they go, "Oh, my goodness, don't tell me I'm getting dementia," rather than going, "You know what? I've got a lot on my plate. I'll give myself some slack and relax." And the more we get stressed about things, obviously, we know that the memory performance goes down.

So, the first thing I say to women is, firstly, they're the wrong age, because only 5%...very few cases are what we call early onset between 65. So, wrong age. And completely different things are going on in your brain, one is a normal process, one is a disease process. And so let's look at what's going on in your life that may be contributing to the sense that you're forgetting. And I see women and they come in, and as a neuropsychologist, women present to me with these concerns for their memory and they say, "You've got to give me a memory test. I think I've got dementia." And you know what? I've never diagnosed any one of them with some early-onset dementia. There's always other things going on.

Emma: Yeah.

Nicola: The other thing that happens, which I think is really, really interesting is that because women are dealing with all these body changes and poor sleep and having trouble remembering things, they lose a lot of confidence. And the research shows that any cognitive changes just disappear over time. So, that's the first thing. But secondly, it's the loss of confidence that's the problem. So, when I look at women in employment, there is absolutely no change in their level of cognitive function or their capacity to perform and work on neuroscience tests at all. When I say this, it's not in a dismissive way that I want to invalidate anyone's experience, but it is all in their head because of lack of confidence and concern. And there's a lot going on in a woman's life during menopause that might be contributing to a loss of confidence.

Emma: Yeah, and I think that's a big one to remind patients of and to normalise that with them, that there is a lot of other things going on and their brain is adjusting to less oestrogen and there is a slowing down of their memory retrieval, but also to zoom out for them and say, "Okay. But what else is going on?" And maybe digging a little deeper on that loss of confidence because that will play a huge part in their experience of their memory as well. And also I like the part about the flat out, "Oh, no, you're the wrong age for dementia," because I think that alone is really reassuring for women when they are in this sort of really difficult situation. Yeah, I love that.

Now, you mentioned in your book, I think it was a 2013 study involving 200 postmenopausal women who were randomly assigned to receive oestrogen, testosterone, or placebo for a month. And then cognitive testing showed improvements in those taking oestrogen and testosterone in as little as one month. Now, I was quite blown away by that. But do you see a place for hormonal therapy in this process? When would you refer somebody for hormonal therapy or when would you think that it would be a good idea? And when would you not think it's a good idea?

Nicola: Right. So, this is one of those areas in this conversation of neuroendocrinology, looking at neurohormones, oestrogen, progesterone in treatments, and in particular on the neurocognitive disorders. The research is not conclusive yet at all, at all. And the World Health Organization has actually tried to put the brakes on this because some people are sort of rushing forwards. And the counter indicator is to prolonged oestrogen exposure are quite significant. It's not a lifestyle option. Obviously, I can never have hormone treatment myself. And I don't... But that doesn't mean I'm anti-hormone treatment at all. I need to state that. Some women absolutely benefit from hormone treatment. 

The recommendation is sort of five years maximum because of the counter indicators. And the counter indicators are there when we look at neurocognitive disorders. Now, the reason people are getting excited about them is because it does appear that oestrogens inhibit the amyloid deposition.

So, I mentioned that neuropathology of Alzheimer's disease, again, it was the most common form, involves plaques and tangles. Now, we talk about tau proteins and amyloid deposition. Now, oestrogen appears to inhibit those things going on. So, it seems that there is a positive upstream impact preventing the formation of those plaques. So, that's why people have been looking at it as well as obviously the cognitive tests that show that people's memory has improved. And certainly, lifetime exposure to oestrogen seems to be a positive. 

However, there's always a big however, there are so many things involved in the neuropathology of Alzheimer's. No one has identified any single cause at all. It seems that there are multiple causes, and therefore, even if exposure to oestrogen was helpful in these cases like that study I showed you, there are multiple causes to Alzheimer's and it obviously isn't a panacea, so it's not impacting everything. And as I mentioned, there's certainly evidence to suggest that life-long exposure to oestrogen has greater risks than benefits at this point in time. 

So, at this point, if you asked me my personal opinion, I would say I'm not convinced the research is conclusive yet to go forwards.

Emma: Okay. That's a really good insight because we do get women coming into clinic that might have read something and they just want to go on oestrogen therapy. And of course, we refer them on to the appropriate practitioner, but it's really great to have that insight from you as well, that the research just isn't quite there yet. And the risks may outweigh the benefits in a long-term situation. 

Now, you also mentioned in your book, a 2011 study. It was a small one, but I found it really fascinating. So, it was on eight males and eight females. And it used brain imaging. And it showed an increase in grey matter, so, your movement, memory, emotions at ovulation. I know I'm certainly more mentally switched on and energetic around ovulation. That's very clear to me. But what does that mean for women who are postmenopausal where they're not getting that increase?

Nicola: Yes. So, that study was part of the research I mentioned earlier that shows that... People have said that women are different every day because of their hormones and it's been used to criticise women and say they're not as capable as men because of our hormones. And the reality is our hormone levels are different every single day and that is absolutely amazing and it makes us awesome. 

So, this is part of the brain managing the changes in oestrogen levels across the menstrual cycle. And this is very new research. And there are more studies in this area now and it's... Again, I keep saying the word exciting, but, I mean, I'm such a neuro nerd. There are more studies coming out and looking at these changes and how the brain buffers against those changes. 

Now, that happens during our reproductive years, during menses because the brain needs to. But in menopause, we don't need to. The thing about being in post-menopause is that we have this constant consistent supply, and our brain will manage that for itself if we haven't got enough oestrogens flowing around in our body. So, we have this wonderful consistency. And I guess, one of the things, particularly to someone like Donald Trump who criticises women for their hormones. A postmenopausal woman has a consistency of emotional neuroendocrine experience as a man.

Emma: Right.

Nicola: So, we have this consistency. So, basically, there are differences between male and female brains, and we see that en utero, it starts en utero. There's more similarities than differences, but there are definitely differences because of our neuroendocrine lives, our sex hormones. And we grow up very similar until puberty, and then males and females completely diverge. And then post-menopause, they come back and converge again in terms of multiple areas, including health risk factors, for example. So, we didn't talk about vascular dementia. Oestrogen is protective of women against vascular dementia and cardiovascular disease, pre-menopause. Post-menopause, women's risks for cardiovascular disease and vascular dementia become the same as men.

Emma: Right.

Nicola: So, we lose some of the benefits, but there are also positives.

Emma: I love that, because when we're working with patients, they're describing all these mood swings and things are erratic. It's really great to be able to say to them, "No, this is a transitory experience. Your brain is adjusting to different levels of hormones. And on the other side of this, your brain won't have those fluctuations and, therefore, your moods and emotions may be more steady." Is that right?

Nicola: Well, yes, it is. And no, it's not.

Emma: Okay. Okay.

Nicola: Yeah. Because we don't know why people's moods are going up and down anyway. But from a neuroendocrine position, yes.

Emma: Yes.

Nicola: They will be steady.

Emma: Yes.

Nicola: So, there's a whole new field. And if I was 30, and not in my mid-50s, I would love to get into the neuroendocrine psychiatry area. And that's the area that's looking at all of this.

Emma: Okay.

Nicola: So, it's looking at the relationship between hormones and emotions and why things affect us and they don't affect us. So, it's all about the mind-body brain connection.

Emma: Yeah. And look, as a naturopath, I find that fascinating myself. And we also see that chicken and egg situation, that bidirectional relationship between hormones and emotions and how menopausal symptoms affect emotions, and then conversely how emotions affect hormones. I mean, they're so intricately related.

Nicola: Yes, they are. And it is absolutely a chicken and the egg. So, you need to put the brakes in where you can to break that cycle. And I guess that comes back to the comment I made at the beginning, that we know that women who anticipate a terrible menopause have a terrible menopause. I mean, how does that work? It's because they have a thought in their head and they set themselves up for an emotional responding, a stress response, and we know that that burdens the body and brain, and that increases symptoms. 

So, I mentioned before about oestrogen effecting serotonin, in particular, oxytocin, endorphins, and, of course, it impacts cortisol. So, what's going on? So, oestrogen and progesterone are both known as psycho-protective neurohormones, which means that they benefit a person's psychological wellbeing. And what they tend to do is reduce cortisol and the sympathetic nervous system response, which is the stress response. And so when you're go into menopause, obviously, you're more likely to have a heightened stress response. And this is something that women reported to me when I interviewed them for the book, they said, "Things that didn't use to bother me, now really do. Things now stress me out that didn't." And so they become... People become more reactive.

Now, the other thing that happens when oestrogen goes down, those nice psycho-protective things also go down. So, serotonin that we have for normal mood, we know that it goes down. We know that the endorphins go down, oxytocin goes down, so feelings of trust and bonding and security in relationships go down. So, you can just see how you're feeling less connected to other people, you've got a heightened stress response, you're having less normal mood, serotonin going on. You can just see that you're going to be more vulnerable. And if you add on top of that stress and worry and other emotional things that you're just getting yourself into potentially a really negative cycle, which is why it's really important to be optimistic and hopeful and positive.

Emma: Yeah. And I mean, clinically, I think I definitely see it, that serotonin levels in menopause, women come in and they're also feeling depressed. And I often have thought to myself, "Look, I know there's a lot going on in this woman's life. She's got ageing parents. Her kids are needy. She's working." But I've often wondered whether on that brain side of things whether that lack of oestrogen primes her to be more likely to be depressed anyway.

Nicola: That's right. And the American Psychiatry Association, I'm pretty sure it was 2010, actually came out with a statement about menopause being a risk time for some women for depression and anxiety.

Emma: Okay.

Nicola: It's quite significant, particularly for those women who already have a previous history. So, if anyone's had a previous history and they've got over an episode of depression or anxiety, absolutely important to just be kind to yourself. You may actually have to seek pharmacological treatment or some kind of treatment for your depression and anxiety during the menopause transition because we know decrease in oestrogen increases stress, decreases capacity for normal mood. And I think a lot of women not only perhaps go down for hormone treatment or they have their concerns dismissed, I think a lot of women are very vulnerable. So, we know that the diagnosis of anxiety and depression increases for women in midlife.

The other thing, which you've alluded to, is what I call the trifecta. So, this is the time...the trifecta of women's lives. One is the hormone stage, so neuroendocrine changes are happening that makes some women vulnerable. They're going through menopause. There is the life stage that you're talking about, so kids leaving home, emptiness, managing parents. And there's also age. And one of the reasons in Western societies that menopause is held up as such a negative thing is because it was considered at a time when women were old, past it, redundant, became superfluous and redundant in society. 

Now, we know that's not the case now. But in the '60s, there was major advertising campaigns that basically said that a woman of menopause age was over the hill, past it. And that's what we're fighting against in this negative dialogue. So, there's the trifecta of negative factors that may be leading women to feel depressed and anxious and it might have nothing to do with the menopause, per se.

Emma: Yeah. And I think there are really good points. And I mean, I think, yeah, it was menopause society, the Australian Menopause Society, said that menopause of women constitute 40% of all healthcare visits in

Australia. So, if we as practitioners can help support our patients better, I think we need to do it. And we also need to have those very frank and open conversations with our patients about what's going on for them.

I'm curious, though, from a clinical perspective, how long do these changes to the brain last? How long does it take until the brain adjusts to those lower levels of oestrogen?

Nicola: Well, that's going to vary between individuals. So, it depends on the duration of their perimenopause and their menopause before it resolves. So, it's going to be an individual thing. And the important thing here is what clinicians can do to help women help themselves because we understand they are profoundly...a vast array of lifestyle and mindstyle changes that women can adopt. And this is why my book is optimistic and I'm really encouraging women to embrace this time. There is so much they can do for themselves to make menopause easier and improve their health now during their midlife and for their late life. So, often people want to take a hormone treatment to get rid of everything, but you know what? There's so many other things people can do, diet changes, all sorts of things women can do. And so these things will impact how long they experience the discomfort of menopause.

Emma: Yeah. Okay. And I know from the research that quality of life scores do tend to drop in menopause. And as naturopaths or clinicians, there's so many diet and lifestyle practices that we have in our toolkits to support these women. And often women will come in and they won't maybe have been into their health as much but because they're in a bit of a crisis, they're now ready to tackle and make those changes that are going to embed and really help support them. So, what strategies do you recommend for reassuring menopausal women that they're going to be okay and that these symptoms are a transition?

Nicola: Yes. Well, I think sort of three things. To start with, first thing is absolutely education. I have been so surprised by the lack of information women have about their own bodies, about how incredible they are. So, always educate, educate, educate so that women...because education means people have understanding and opportunities and options.

Emma: Yeah.

Nicola: The second thing, another E, so educate, is empower women. Often women have been disempowered. I've had a lot of women, I’m not the first person they've seen. So, often I'm the last person they see. So, they've had their experience invalidated. Women are still sent away with, "It's all in her mind. There's nothing wrong." So, women need to be empowered to take responsibility for their health and know that they have incredible capacity. 

And the last thing I think clinicians need to do is encourage women. And this comes back to the first commentary. We need to encourage positive acceptance and let women know this is normal and healthy and it is a phase. I talk about the two bookends. And the first bookend is puberty. And most women get that. They understand that it went on for a couple of years. And then I said, "But this is the second bookend. You just treat this like a second puberty, but this time it's going down, not up." So, it's just a bookend around that middle phase of your life. And you've got this third stage of your life, which is, you know, late midlife and late-life beyond. And it's called life now, not age. I mean, these are terms we need to use. We're talking about midlife and late-life.

Emma: Yeah. I really like that. And then I think that those key points, education, empowerment, and encouragement are profound. And we are perfectly placed to do all of those things and to do them really well. So, I'm definitely going to be taking those three tenants on board when working with menopausal women. It would be great if we could walk away with your top three strategies.
Nicola: Well, I wanted to end with an ACE because some people feel that menopause is a dud hand, it's part of life, but it's the time of challenge. And if you feel that you've been given a dud hand, it's really important to play your ACEs without overworking a metaphor. 

So, ACE, A-C-E. And the first thing to do is acceptance. So, as a clinician you know, accepting the client's story, validating their experience, giving them information, but encouraging them to accept it. Menopause, it will pass, it is normal, and there are things you can do. So that is part of the acceptance for clinicians to help guide their clients and also for clients themselves to walk away saying, "Okay. The first thing is to accept this as a natural transitionary stage." 

The C stands for caring and kindness. Now, I know I've got 11 strategies in my book, but having had 28 years at the coalface as a clinician and a researcher, what I understand is unless people practice caring and kindness, they won't actually do anything.

Emma: Yeah, that is such an important point. Yes.

Nicola: Yeah. So, if we encourage people to be kind to themselves, and I really do invite women... Often we are the primary carers to everybody around us. Now is the time to embrace and care for yourself. So, care for yourself and give yourself kindness. We are faulted human beings, but we are perfect with our imperfections. So, now is the time to embrace self-care and kindness because if you're not kind, you won't engage in the health behaviours that the treating clinicians suggest, be it augmenting vitamins and mineral supplements, or HT, or exercise routines, or sleep hygiene, all those things. Nothing will happen without that. 

And then the third thing is to find enjoyment. Engage and enjoy what life has to offer, and find the good. And sometimes, as clinicians, we have to help our clients with their engagement. And as clinicians, we all have clients who we know are ambivalent. So, it's really important that we get that engagement, maybe people do practice motivational interviewing and things like that with their clients. And we have to keep that engagement and make it something that is achievable and engaging and enjoyable for people.

Emma: Yeah, yeah. I love that acronym, ACE. Acceptance, caring, and enjoyment. I think practising those three things are going to go a long way towards helping women through that experience of menopause.

Nicola: I hope so too because menopause now just marks the midpoint in your life. So, it's perfect time to say, "Right. No. I have no recrimination for what's happened in the past, but actually, completely embrace the future."

Emma: Yeah. Perfect. Nicola, thank you so much for spending time with us today, discussing how menopause can affect our brains and our wellbeing. It's a challenging time for so many women. And a couple of key takeaways for me, the transitory nature of changes in brain function as the brain adjusts for lower levels of oestrogen. It really is a stage. 

And the critical aspect of lifestyle medicine for menopausal transition, scheduling those pyjama days, and then the education, empowerment, and encouragement that we need to do in our practice. 

So, once again, Dr Nicola Gates, thank you so much for joining us today.

Nicola: Perfect. Thank you, Emma, for the opportunity to talk today.

Emma: Not a problem. Thanks, everyone, for listening today. Don't forget that you can find all the show notes, transcripts, and other resources from today's podcast on the FX Medicine website. I'm Emma Sutherland. Thanks for joining us and we'll see you next time.


About Dr. Nicola Gates

Dr. Nicola Gates is a Clinical Neuropsychologist, researcher and author who has channelled her knowledge and expertise into two careers. As a registered neuropsychologist she has a small private practice in Sydney, works with adults and has internationally recognized neuroscientific research with multiple peer reviewed publications. As a health promoter Dr Gates, aka the neuro-nerd,  has written two best-selling combining neuroscience with health information and strategies titled A Brain for Life and The Feel Good Guide to Menopause, published by Harper Collins, and presented to thousands of adults to promote optimal health for brain, body and mind.  Her books, like her clinical work and presentations, combine over  twenty years’ clinical experince with medical research to promote optimal life-style and mind-style strategies for total health and positive living. Her other passions, aside form her children, are gardening and bee keeping.


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