HRT and Hormones Part 2 with Dr Ghazala Aziz-Scott

In this episode I welcome back Dr Ghazala Aziz-Scott, Clinical Director at the Marion Gluck Clinic. We continue our conversation around perimenopause, menopause and HRT and also expand the conversation into women's brain health.
Dr Aziz-Scott helps clarify the information around the risks and benefits of HRT, what hormones apart from oestrogen and progesterone might be needed and the different methods of delivery available.
Ghazala does an excellent job of explaining the differences in how HRT is given in the conventional space compared to how it's offered  at the Marion Gluck clinic .
However you choose to get your HRT, this is an invaluable listen to help you answer your questions around HRT. 

Links mentioned in this episode:

Marion Gluck Clinic
EPIC Trial
American Academy of Anti-Ageing (A4M)
Food for the Brain

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Transcript

Dr Ghazala Aziz-Scott Part 2
Tue, Apr 23, 2024 1:15PM 56:36
SUMMARY KEYWORDSoestrogen, women, hormones, progesterone, people, hrt, doses, brain, compounding, menopause, testosterone, ageing, dhea, treatment, conventional, sex hormones, health, regulated, important, body
SPEAKERSDr Ghazala Aziz-Scott, Peter Williams 
Peter Williams 00:03
So part two of our delve into HRT. And the reason why we had to do this because I would say almost 85, if not 90% of the people who listen to my podcast are females, and generally between 50 and 70. So this is literally the podcasts and the podcast for them. And we've got Dr. Ghazala Aziz-Scott back in. Ghazala as you know, is the is the Clinical Director at the famous Marian Gluck clinic, we increasingly work together on patients I send her patients that I'm pretty sure need an expert like her and her team with regards to HRT, because I think if you've listened to our podcasts, and that's the thing you need to do, we've got two parts one we've already done, which is a bit of an overview that Ghazala did, and talking about the differences and she's gonna sort of get, we're gonna get her to summarise that again. But then we're today we're going to jump into a little bit more detail about compounding materials and medications, but also some of the sort of more aspects that we tend to work with as well, which is like the joint health, the brain health, the cardiovascular risks, etc. so Ghazala, thank you so much I know you're busy lady, and I'll definitely take you out for dinner is that when it gets a little bit warmer? So look, we did sort of a really good introductory podcast, this is a big subject. And, and again, you know, as I said to you the I think maybe it's the way, we've got to get the general public to understand just how complex human health is. Because I think, you know, we've been brought up the, it's quite simple. And the reality of it is that it's so complex, even the best people pretty much would suggest we've got some idea what we're doing but it's so complex, and it's it's such a moving picture, that we've always got to take a patient where they're at currently, but also make sure that we don't leave them too long, because things always change. And obviously, as I said that, you know, you need real experts to understand the difference. With regards to I think where we are, we're gonna call it functional medicine or systems thinking medicine as it applies to HRT treatment. So that's why if we have patients who come to our practice, who we definitely are very menopausal or early menopause, then it's a question of, we think you need to go to speak to these guys, because you've got to be doing this day in day out in that specialised area to really have a pretty good understanding of what we need to do and how we need to do it. So I know we did part one, and part two, we want to jump into a little bit more detail. So can we just just very briefly summarise where we've gone for the last 20 years because HRT was big. And then the women's initiative study came out in 2002 that said, Oh, hang on, we need to maybe just take a relook at that. Can you just very briefly go over the history and where we are now. Sure.

Dr Ghazala Aziz-Scott 03:20

Sure bioidentical hormones or HRT has been around since the 1930s and the 1940s. But one of the major issues was the cost of it because they were extracting it from the ovaries of sheep and, you know, horses, urine, etc, etc. So it took a long time to find solutions to make it viable for mass production. And the pharmaceutical industry obviously cottoned on to it because so many women are perimenopausal and menopausal, when they knew that, you know, this was going to be a big seller. And indeed, Premarin was one of the biggest sellers in the US just before the Women's Health Initiative study. And oestrogen was touted as you know, feminine forever, you know, how women could still remain useful. And at that time, you know, the the other benefits and risks hadn't really been evaluated. So, as HRT became more and more popular, there was obviously the counter, you know, that the counter argument of well, what is the real impact of this on women's health? So the Women's Health Initiative study, took a million women, and they looked, they gave them HRT, and they looked at the rates of cardiovascular disease, and breast cancer risk, strokes, clotting, osteoporosis are all the things that HRT is supposed to be beneficial for it was looking at, well, what's the evidence for this? And that trial had to be stopped three within three years because they were finding that there were increased numbers of women who were having heart attacks and strokes. So they stopped it. And at that time, there was this massive Media flurry. And lots of women came off their HRT. There was so much scare mongering. And doctors also became frightened about prescribing HRT. So we had about 10 years where HRT was a no, no, you know, it wasn't being prescribed. And doctors also lost kind of 10 years in their understanding of that situation. But then in 2012, that data was revisited. And what they found was that the women who had been enrolled in that trial were over the age of 60. So they'd been menopausal for quite a long time. And they had pre existing cardiovascular conditions, which would predispose them to getting heart attacks and strokes anyway. And they found that the increased breast cancer risk was due to the use of synthetic oestrogen and synthetic progesterone. So synthetic progesterone, which were used, also had adverse cardiovascular risk profiles. So they found that it was a wrong age group of women. And also we were using synthetic HRT and oral estrogens. We know that oral estrogens also increased the risk of clotting. So now the data was revisited and there were subsequent studies. There's one called the Epic Trial, which was done by Fournier et al and I think it was in about 2008. And they showed that if you use transdermal oestrogen with oral micronized, progesterone, your risk of breast cancer is actually not increased. You know that the risk is the same as the baseline level risk of breast cancer for most women is one in six. So it's a high risk anyway. So that that's that so now we know that, you know, when you're using the correct forms of HRT, and even, you know, we in the in the bioidentical world, obviously, we've been doing this for a while, but it was in 2019 that the NICE guidelines, so that's the National Institute for Clinical Excellence. They said that bioidentical hormone replacement was the way forward and for most women, the benefits outweigh the risks. And the British Menopause Society have followed suit. We know that, you know, again, the gold standard is bioidentical hormone replacement, which you can get both in the NHS, the conventional sector, and in the private sector. You know that when they're in the conventional sector, they are called body identical, and they usually regulated doses from the pharmaceutical industry. Whereas in the bioidentical compounded world, we will make up those doses to individualise them to women in different formulations. So that's the difference between the two. So

Peter Williams 07:44

let's work on that. Because I think the key thing is, is that I suppose, like everything, the risk is that you have a industry standard dose, that may or may not be appropriate for a patient, so can you understand the difference and where that may get a little bit, or that might be inappropriate for a patient, ie, they might get too little, they might get too? Too much? Sure.

Dr Ghazala Aziz-Scott 08:12

You know, I'd like to emphasise that, you know, the regulated bioidentical hormones that we get on the NHS are excellent. And for many women, they work very, very well. I think one of the disadvantages in the you know, the conventional sector is women are not monitored. And so we don't check the levels of hormones, we're not doing the same safety checks that we should really be doing, for instance, you know, in the clinic, and you know, our recommendations that are that women should have a baseline pelvic ultrasound, then have an ultrasound, but a pelvic ultrasound every year to 18 months to monitor their pelvic health. So so these are the things that are really important in in monitoring the safety. So when we're looking at regulated treatments, I mean, we have a huge range of estrogens available, we have patches, we have gels, we have Lenzetto spray. So there's lots of different methods of delivery that do work quite well. However, something like Estrogel, you have to use the maximum doses about four pumps. And if you get a four pumps of Estrogel in your in your palm, it's actually a huge gloop of, of gel that you then have to rub all over your body. So there is also this risk of transference to other members of your family to you know, there's been cases of dogs developing nipples, and also compliance factor. Because if you've got to smear that amount of gel all over your body every day, you know, it's not particularly pleasant. The other thing is it's got an alcoholic base, which can sometimes disrupt the stratum corneum of the skin. So the benefits of the compounded Estradial is that we're able to concentrate the same amount of hormone that's in a big group of four pumps of oestrogel into 2.3 mils of a cream and the base creams that we use in the specialist pharmacy, they are of high absorbency. So we can actually, I think the products absorb a lot better. And they're very convenient because one, you know, a pea sized amount of cream that you rub on your forearm is a lot more convenient than four pumps of oestrogel. So that's one example of oestrogen. Now, we know that some people don't absorb oestrogen transdermally very well. And as we continue that treatment, sometimes they become less efficient at absorbing it. And so in the conventional sector, you would then have to move to an oral oestrogen preparation, then we know oral oestrogen is have got increased risk of clotting. And they have an adverse effect on the lipid profile compared to transdermal oestrogen, they can also increase blood pressure. So there's a lot of other cardiovascular risk factors that are affected by the

Peter Williams 10:58
What's the mechanisms that drive that it's just that just that it's not just that I say, I sort of don't quite understand the mechanisms. Why,

Dr Ghazala Aziz-Scott 11:09

Maybe it's something to do with a first pass effect. And and also, the effects on their lipid profile. It's so complex. I'm not sure exactly what but we know from the studies that oral estrogens do have an increased risk of cardiovascular disease. And I've just been to the A4M (American Academy of Anti-Ageing)conference in Miami. And they again, they pointed out that there is an increased risk of hypertension with oral oestrogen compared to those probably you know, because they do have an impact on lit on the liver. (I was gonna say they are hepata toxic) . There'll be an impact of the liver, I imagine that maybe doing that. So so therefore in the in the compounded space, we if someone's not absorbing transdermal oestrogen very well, we can give them sublingual, oestrogen, which is underneath the tongue. So essentially, we can make give them a lozenge or sublingual drops where the oestrogen is absorbed directly into the circulation underneath the tongue. So transdermally it sits in the subcutaneous fat tissue, and then it's gradually absorbed. So it gives you quite a potent dose of hormone but it doesn't go via the liver. When you take orally, oestrogen is digested in your gastrointestinal tract, and then it does pass through the liver. And so you know, there's more risk of toxicity. Now, when we're looking at progesterone, for instance, progesterone, there's only one form of bioidentical progesterone available in the NHS and conventional space. So that is oral micronized progesterone. And the dose of that is to take usually, you know, in a menopausal woman would be to take one 100 milligramme capsule at night. Now, oral progesterone has a lot of benefits, in that it's digested within 20 minutes. It produces a lot of neurosteroid metabolites, which have a really beneficial effect on the brain. So they interact with the GABA receptors, you get a lovely calming effect, anxiety, insomnia, those sorts of things are much improved. However, some women don't tolerate oral progesterone. And the other thing is Utrogestan has a peanut oil release mechanism. So if you've got an allergy to peanuts, you may not tolerate progesterone very well. The other thing is we've got no way of halving the dose, you know, we can't start at a lower dose. So 100 milligrammes is the dose for endometrial protection so that's the licenced dose of endometrial protection. However, the British menopause society are realising that if you are having higher levels of oestrogen or you're someone who absorbs oestrogen quite well, 100 milligrammes may not be enough, so even they're recognising that if you bleed on 100 milligrammes of progesterone, you might need to take 200 milligrammes but again, you go from 100 to 200, there's no halfway house. Now, if you don't tolerate oral progesterone in the conventional space, the other way of delivering it is via the vaginal route. So it's not a licenced way of giving progesterone, but women can use the Utragestan vaginally on alternate days. And that seems to give endometrial protection, how much progesterone is absorbed into the circulation from a systemic point of view, you know, is is debatable. The other thing is, you get a lot more progesterone, that's unadulterated within the system when you're using it vaginally, because it's not being digested orally. So whether the vaginal root has the same effects on calming the brain down and the same effects on insomnia is again, it just varies for each individual woman, how they metabolise their progesterone. So that's the other important thing is it's not just the hormone is how you're delivering it. And it's each person's individual physiology that will determine the impact of that hormone on that person.

Peter Williams 15:11

This is a really important conversation because the reality is we're giving people and we're giving, you know, females and my wife's one of them this sort of understanding that it's, it's, you're going to be pretty damn lucky if you just have a conventional intervention. And that works really smoothly. Yeah, because those hormones have to dance with other hormones as well. And you've got to take all that into account. So can you expand on, you know, the things that you think about straightaway? It's not just the it's not just the oestrogen is it's not just the progesterone.

Dr Ghazala Aziz-Scott 15:44

No, no. I mean, we must talk about testosterone. So again, testosterone in physiological doses is really, really important for women. So you know if, this is recognised in the conventional space, but there is no there's only recently is there a licence compounded testosterone preparation that's suitable for women. Prior to that, and even now, women are being given testosterone for men and being told to use a tiny dab of it or there's no there's no rules or regulations. So Tostran is a male testosterone preparation. It's got 10 milligrammes in a pump. Now, we would give women between 0.5 and 2.5 milligrammes, you know, and we make sure we get the physiological dose for them. So that's quite a big difference and some women are told to take one pump every other day, you know, so they can get very large physiological doses of testosterone, and they get the side effects with it. Now, with testosterone, it's really interesting. The, so in men, low testosterone does increase cardiovascular risk with women, physiological doses of testosterone are beneficial to cardiovascular health, but if the doses are too high, so for instance, women with PCOS, they have an increased risk of cardiovascular disease. Obviously, there are other factors in PCOS. But in general, the physiological range is important. So it's important to test and measure it. And, and to be you know, to be sensible. So now the British menopause society is saying, Well, if you can't get hold of, you know, compounded testosterone that's available. It's called Androfemme. And it's a compounded testosterone that comes from Australia, but it's licenced in Australia. So therefore, we can prescribe it in the UK, but only privately. So even though it's licenced, you can't get it on the NHS because it would just be too expensive. So, we obviously we compound it in the specialist pharmacy, the beauty of our treatments as well, is that we can mix it in with the other hormones. So, you know, instead of someone having to buy the testosterone separately, you know, once we've got people stabilised, we can actually mix oestrogen, progesterone and testosterone together in a cream or a lozenge so there's a lot of more convenience, in terms of of the treatment.

Peter Williams 18:05

I think what you're also discussing here is that you can get I mean, whenever I mean, this might be brand new to people, but you know, I have an understanding about actually, when you start to understand the way you're speaking, these are really important things from a point of view of compliance is key on everything. And the more difficult it becomes, the less likely you're going to get the results. But you know, and I think it becomes more comfortable that you understand, well, what am I paying for privately and it says all these nuances that you're talking about? You probably just wouldn't, wouldn't have been thought about on unless you're a systems thinker, understand the bigger picture of everything. And then and this is I think this is where the specialist compounding pharmacies absolutely make this a game changer as well. So can you I know we touched on this last time, but can you expand that because obviously, you have a compounding pharmacy that runs everything for you. So can we can you give us what that is? How long it's been going on? I mean, it's normal in the US.

Dr Ghazala Aziz-Scott 19:08

Yeah, so compounding, I mean, you know, the days of old, compounding was how we made our medications. So, you know, all pharmacists have to be trained in how to compound medications. And so there's a cultural variation between different countries. Now, obviously, with the advent of, you know, big pharma, compounding has kind of got out of out of the window. And also in England, we have a population based medicine systems. So, you know, we've got very much the philosophy of, you know, one size fits all for the greater good. So having regulated doses helps, you know, doctors follow protocols, it helps, you know, work out the economics of the health system. However, you know, compounding is incredibly important. So the benefits of compounding so compounding means that we make up the medication in a compounding pharmacy in a range of different formulations. So the benefits of compounding is that we can individualise the doses. Now we tend to start it and start people on low doses. So I'm sort of, you know, I'm quite conservative in the way I prescribe my hormones, and I start low and go slow. And I only give people enough to give them the systematic systemic benefits of those hormones get good levels in their bloodstream. But you know, I look at the picture, I look at their symptoms, their risk factors, and I'll start them on low doses and workup. And then, you know, we've discussed the issue of, if you can't absorb your hormone, transdermally, we've got other methods of delivery. So we can give people sublingual troche, we can give people, sublingual drops, we've got rapid dissolve tablets, we can do vaginal preparations of testosterone, there's a lot of different things we can do to try and get the right balance for that patient. And there's, you know, there was intuition in it, obviously, when you've been doing it a long time, you kind of have an idea of what's going to work for people. Compliance is huge, because, you know, people are going to be taking this HRT for decades. So unless it's convenient, it's incredibly, you know, it's an incredible, you know, inconvenience to be putting on lots of different preparation, always remembering to take your tablets at night, you know, imagine having to put vaginal progesterone in every other day, you've got to put a vaginal preparation and you know, it's not particularly pleasant, really. So you know, it, we can make things a lot more pleasant for people a lot more, you know, a lot easier to comply with things. And so one of the, the, you know, the things that comes up is, well, this is unregulated. And actually, the compounding pharmacy is regulated by the general pharmaceutical Council. And so they expect the same standards of production that you would expect in a in the pharmaceutical industry. So we are regulated by the general pharmaceutical Council. The problem is there's lots of, you know, compounding pharmacies, internationally, that, you know, aren't necessarily regulated. But certainly, if you're going for compound treatments, it's important to go to a compounding pharmacy that is regulated by the general pharmaceutical Council. And when we when we say unlicensed, what it means is that because we're personalising the doses, that's why it's classified as unlicensed, but the actual raw products of the oestrogen progesterone and the testosterone, they're all licenced bioidentical hormones that we are getting from the same sources that you'd get them from that the pharmaceutical industry get them from, so they're only classified as unlicensed because we make them into personalised doses, not because the actual raw ingredients are, are a problem. And you know, in fact, if you use vaginal progesterone, so if you use Utrogestran vaginally, that's classified as unlicensed, and you've got to remember that all paediatric medicine so we don't do controlled clinical trials on children. For doses we give them the equivalent, you know, smaller doses of adult medications. So it's not that, you know, every single thing in medicine is about a controlled clinical trial. You know, paediatric doses are not. So we are we are we do do unlicensed things. But, you know, what's so important to remember is that, you know, when we give people you know, personalised doses, we're actually monitoring them, you know, we're looking for the safety, we're looking at the levels, we're looking at the general health of the patient, we're looking at other things that interact with the hormones. You know, we're looking at so much more, you know, the other thing that so DHEA is another very popular hormone that we use in a compounding pharmacy, and there's still a lot of research that needs to be done as to you know, its its precise benefits now, DHEA so it stands for Dehydroepiandosterone comes from the adrenal glands. And it's a precursor to many of the sex hormones depending on which cell that DHEA goes into. And DHEA actually has estrogenic effects within a cell. So it's instead of an endocrine molecule is known as an indocrine molecule because it actually has an effect on the cellular on a cellular level. It can improve oestrogen, it has an estrogenic effect. And I find DHEA again, hugely beneficial because DHEA converts into other androgens that are important for women as well. So testosterone isn't is the male hormone but the other androgens are equally important. So if you've got low DHEA levels, those other androgens may be lower. So a little bit of DHEA can actually have a hugely beneficial impact on that sort of general balance of someone's hormones. And it can be very energising, you know it has anti ageing properties. It has benefits for the immune system. So again, you know, I don't have to hike up people's oestrogen doses, you know, we added a little bit of DHEA. We've got some oestrogen effects within the, you know, at the cellular level, that's not increasing serum levels of oestrogen, which can then have negative consequences. So this is, you know how we can.

Peter Williams 25:18

So I think what you're saying is that there's it, there's a huge sort of hormonal web with so many more hormones that are involved. I mean, you only have to look at the steroid hormone pathway. There's a lot of things there. And there's a lot as I said to you, there's a lot of neurosteroids it really help the brain as well. Yeah. And your job is, I suppose, is to symptomatically look at the bigger picture and then dose from a point of view of how do you keep the balance across as many pathways and hormones as possible? I mean, you run that over for about three months and then do you recheck or what what's the usual

Dr Ghazala Aziz-Scott 25:54

Yes, so um, you know, my starting protocol, I mean, when I start people on I mean, it depends on whether they're perimenopause or menopause or so this is another really important key fact is a lot of women who are Peri menopausal, meaning that they are in that period of time before the menopause. So the menopause is classified as the absence of of menstrual cycles for 12 months. perimenopause is that period leading up to it where your hormones can be all over the place. Now, in that pattern of hormones very often we have progesterone deficiency, as the primary presentation, so progesterone deficiency is insomnia, anxiety, palpitations, a lot of women as that breakdown occurs between your brain and your ovaries can go into increased oestrogen mode, so they can become quite oestrogen dominant when the ovaries can go into overdrive. So a lot of these women can be quite oestrogen dominant, and they're presenting with symptoms of progesterone deficiency, but in the conventional space, they are given both oestrogen and progesterone. And then they feel absolutely dreadful. And they persevere, even though they feel dreadful for a year. You know, and that's so negative, because actually, when you assess people in a much more nuanced way, we will only give people progesterone very often in the peri menopausal phase, and it works beautifully. transdermal progesterone in the perimenopause works beautifully, you know, and we can look at what other factors are causing the hormonal imbalances. So this is the ideal time for us to support their lifestyle and their diet and, you know, give them some supplements that may also support the body in general also help them with their adrenal. Is that help? Because

Peter Williams 27:34

almost all of the time, women will be given oestrogen. Without testing, it will just be based on symptoms. Yes

Dr Ghazala Aziz-Scott 27:44

yes. So the nice guidelines say that if you're over the age of 45, you don't need to test. Now I see women in my clinic who are 42 and went to their GP and weren't given any blood tests. They weren't you would they just assumed it's menopause. It's hormonal. Let's give you some standard HRT. You know, it's just the reflex reaction. Now we know that women can present with all sorts of things in middle age, they can present with autoimmune disorders, they can present with thyroid problems, they can present with inflammatory disorders. So unless we work out what is causing the symptoms, we can't just give people blanket HRT. But it's frightening how much that happens. I mean, I'm shocked at some of the cases I see where people have just been given hormones, and obviously have had really detrimental effects. to that. Know, this lovely 42 year old lady who had a real history of trauma, who had just been through her young son having cancer treatment where they the whole family had to decamped to Manchester, because that's where they had the specialist treatment for his son's brain tumour in the middle of lockdown. She was clearly completely adrenal ly dysregulated in a high stress mode, which really had an impact on her hormones, and the GP, sadly, just started her on HRT, and she took it for a whole year, you know, and no one looked at her in more detail. And this is, this is not an isolated case. So, you know, the importance of not just saying, Okay, you're, you're 45 You've got these symptoms, you know, people present with quite a myriad of symptoms anyway. So it's really important to be able to break those symptoms down into, you know, clusters of patterns of what could be going on, and then doing some testing. So my motto is test don't guess whereas, you know, in the NHS, its guess don't test. Yeah, I

Peter Williams 29:36
think that's the case. But I also think it's a question of, I honestly feel as though it's very

difficult for GPs to just practice medicine these days. Oh,

Dr Ghazala Aziz-Scott 29:45

I mean, listen, I was a conventional GP. I absolutely loved being a GP. I work for the NHS for 30 years, and I was a partner in general practice for 23 years. So I know what it's like. And, you know, in the old days when we were proper family doctors, you know, I would easily happily spend, you know, time with women, you know, really going through stuff in a much more holistic way. And even when, you know, my time at the Marion Gluck clinic and being a general practitioner overlapped, so I would often give people you know, half an hour consultation in, in, you know, because it was my passion to really helped people with the menopause. I mean, obviously, my tools were a bit more limited, but I could really do quite a lot. And, and I love that, but sadly, the way, you know, general practice is moving, especially after the COVID epidemic pandemic, where, you know, I never ever thought I'd be able to do my job online, or, you know, but you know, that there was such a pull towards, you know, online consultations, telephone consultations, and basically, your average GP, you know, I have so much compassion for them. They are, you know, the NHS thrives on the goodwill of the doctors and the people who work for it. And actually, unfortunately, the the limitation of resources, the way the whole system is structured, that the pressure on hospitals, funding, everything, it's a meltdown. So your average GP cannot do the job to the best of their ability because they're firefighting. Yeah. And so, inevitably, you know, they're going to be thinking of solutions to, you know, problems that they want to deal with it quickly. They want a sticking plaster, because otherwise they can't get through their day, you know. So that's, that's the situation now there is a lot, there
are a lot of conventional private menopause clinics that are now available. So there are private menopause clinics that will give you the regulated bioidentical treatments. And, you know, obviously, that they'll be giving you lifestyle advice and some general advice, but there's no way people have the same tools that we have in the personalised medicine space. You know, I mean, it's such a great privilege to have access to these amazing tests. Yeah, you know, I, I'm just I'm blown away by them, you know. So, for instance, when we're assessing anyone for their Hormonal Health, their adrenal pattern is so important. So our adrenals produce cortisol, which is our stress hormone. And it's very easy for our patterns of cortisol to become very dysregulated. Now, people who have had a lot of childhood trauma, or lots of traumatic life events, they can be very adrenally dysregulated (totally). And those things have a massive impact on hormone balance. So when we think about it, cortisol is our survival hormone. So when we've got dysregulated cortisol, our body interprets that as being in survival mode. Now, if we are in survival mode, there, we can't get pregnant, because that wouldn't be very good from an evolutionary point of view for the offspring because they're being born in difficulty. So therefore, the body has all kinds of clever mechanisms to switch off sex hormones. So what we find is that progesterone levels are often compromised when people are adrenally dysregulated. And cortisol will, if there's too much of it will actually go and sit on progesterone receptors. So even if you're producing good amounts of progesterone, your body may not react to it. So we know that women who have recurrent miscarriages have often have low progesterone, and that low progesterone can often be, you know, a result of, you know, a lot of stress. So there is all of that sort of delicate nuance that we need to take into consideration. And adrenal health is absolutely vital, you know, and then looking at how does the body metabolise your hormones, so if we're giving you all of these hormones, obviously, your body needs to clear them out of your system. So it's really important when we are thinking about, you know, oestrogen, for instance, we know we're giving people oestrogen as HRT, what actually happens to that oestrogen, well the oestrogen goes into the liver where it's activated into oestrogen metabolites, which then circulate around your body attached to oestrogen receptors and have their different effects in the body. Now, there are some metabolites of oestrogen that are more toxic, so the four hydroxy metabolite is more toxic, so women so when we worry about breast cancer risk, we know that women who have developed breast cancer, with HRT have increased very often will have increased levels of four hydroxy. oestrogen, which is the more toxic metabolite, the synthetic oestrogen that people used to be given before did produce more four hydroxy toxic metabolites. So if we know about this, and you know, you can produce more for hydroxy if you have a genetic tendency, or if you have, if your lifestyle is not good, and you're not, you're not eating like sorts of foods that push you down the more beneficial oestrogen pathways. These are all things we can look at so we can optimise people's health, and we can make sure that their HRT is as safe as possible.and actually, we're not just looking at, you know, giving people these doses of hormones, we're looking at what happens to that hormone once it goes into your system. You know, and in functional medicine, we have the PTSD. So we're looking at production of hormones or when we're giving people the hormones, you know, as a treatment, we're looking at the transport. So we're looking at how are those hormones transported around the body, there's this protein in the blood called sex hormone binding globulin, which binds to the sex hormones. Now, when you're taking oral treatments, sex hormone binding globulin goes up because your body reacts to all of that hormone going into your body, or very often, even with a pill, sex hormone binding globulin goes up. Now if sex hormone binding globulin goes up, it also binds to other hormones like testosterone. So the availability of testosterone to your body can go down. So that's an important thing to look at Pt. S is for sensitivity, we're looking at the different sensitivities of the of your receptors. So now we've got ways of looking at how sensitive are people's oestrogen receptors through nutri genomic testing. And so all of those things are very useful, extra snippets of information where we can really personalise someone's treatment. And then the final thing is detoxification, where we want to make sure that those hormones are cleared from the body in a safe and effective way. And that's where our gut health is so important. So estrogen, you know it that metabolism restraint is regulated by the gut microbiome. So again, healthy gut means we're clearing our hormones very well, if we don't have a healthy gut, then we're not going to be doing that. So this is where that holistic approach with this very sophisticated testing available, but even just the basic tenets of functional medicine, when we're looking at the importance of nutritional medicine, we're looking at the importance of lifestyle, we're looking at the importance of stress and the impact on the body, on how well we're sleeping, on our relationships. All of these things have a very beneficial impact on our health.

Peter Williams 37:09

It's interesting, isn't it? Because obviously, the great thing about this is that it I suppose we think about HRT generally on on 2 hormones, and it's not really about two hormones at all. I mean, it sort of is but it, isn't it a question of how do these big two players fit in the rest of the team and, you know, you've got to get them to dance in the appropriate way. I came off. We've talked about this before we went before we started recording, and I wish I'd recorded the conversation but I mean oestrogen does look like. And again, I think this is where there's no doubt it's a key player. And but it's a key player that has to it's almost like you've bought the staff for weed but the staff for weed has to be within the rest of the team. The team's got to play for the star forward. But I went to a lecture last weekend, it was really on about how oestrogen looks like and then measuring it through this the sort of these ageing tests that we've got now that are sort of giving us an indication of biological ageing. And what they were showing is how how menopause completely changed. And perimenopause is completely ageing the immune system and they were showing some really good examples of how, you know, in certain patients, their testing was showing the lack of oestrogen or the wavering oestrogen was producing results that were suggesting that their body was, you know, 20 years older by that test. And the reality is that what probably most females feel as though they're going through once they go into perimenopause and menopause and how important that phase is to get it right. So and I know we discussed this last time. So I think what we're saying on this is that which you would probably agree with that oestrogen is, is pretty much a fountain of youth.

Dr Ghazala Aziz-Scott 39:02

Absolutely. Yeah. I mean, it has so many beneficial effects on the body. So we know that oestrogen is got there 300 different cells in the body that respond to oestrogen. But wherever you have oestrogen, you also need to have progesterone. Because oestrogen has the impact of proliferation. So from a scientific perspective, oestrogen causes cell proliferation so oestrogen on yet on the breast, grows the breast tissue on the lining of the womb grows the lining of the womb. And progesterone has a really important role in regulating the actions of oestrogen. So wherever you've got that proliferation, you need to have the regression. And you need to have the control of how those cells differentiate. So we know that with cancer, you get a proliferation of cells, but they proliferate abnormally. The role of progesterone is to help differentiation as well and control of that proliferation. So it's got a very important role. And in conventional practice, you know largely in HRT treatments, we think of progesterone as only controlling that proliferation at the level of the endometrial lining. But we know that oestrogen has a multitude of benefits throughout the body. So we have oestrogen. I've just done a webinar on Women Mind Mood and Hormones for Food for the Brain.org. So it's basically looking at why Alzheimer's disease is two to three times more prevalent in women than men. Yeah. And so one of the major factors is the menopause. So the menopause results in ageing of the brain. So it's not just the lack of oestrogen. It's also, Estrogen has a very important role in the transport of glucose across the cell membrane in brain cells so that the sort of brain fog that women experience in the in the perimenopause and menopause is caused by low oestrogen resulting in lower blood flow, lower energy levels of brains, we call it cerebral hypometabolism. Absolutely, so oestrogen has a massively important role in its Neurotrophic. So basically, it helps nerve cells grow their, their their little branches, it helps with the connections between nerve cells.

It's also neuro protective. So basically, it protects, it protects nerve cells. And estrogen also has a lot of links with the neurotransmitters that we produce in our brain. So it's got links with the serotonergic nerve, kind of neurotransmitter system, the cholinergic transfer neurotransmitter system. So it's got so many multiple effects in the brain tissue. So it so that's the brain, we know that oestrogen is very protective for our bones we know that oestrogen given correctly is it has a cardiovascular protective effect. So there's many, many functions that it has. But progesterone equally has a lot of different functions in the body. So we know that progesterone is also very, very neuroprotective. We know that some of the other metabolites of sex hormones like pregnenolone, and DHEA, also form neurosteroids. So we know that, you know, they can help the brain recover after injury. So there's so many other applications of the sex hormones that are yet to be, you know, really used to the full. Certainly we use progesterone a lot in the treatment of women with PMS and PMDD. We use progesterone a lot in the treatment of women who've got endometriosis. Where you know, they're quite oestrogen dominant, so that oestrogen dominance can drive endometriosis, but by giving them bioidentical progesterone, we can help balance that, you know, that's, I mean, there's many other factors contributing to endometriosis, but by giving them progesterone we can cause some, we can give some kind of balance. So, you know, by looking at things in this very beautiful, holistic way, you know, we can really get the best outcomes. And, you know, I mean, really, and truly, you know, I think that's the wonderful thing about functional medicine is we recognise, you know, hormones as one of the nodes of functional medicine as the communication node. So we know that the the importance of hormones communicating between all the different organs and cells in our body, it's completely vital. So you know, optimising Hormonal Health, also optimises your general health. And you know, that's becoming more and more apparent. Now, there's a big overlap with bioidentical hormone, science, longevity medicine as well, because we know that you know, that the oestrogen and other hormones are very anti ageing. And the other thing is, if you're in, if you feel good, and you're in general, good health, if you've got that great motivation, you're going to exercise more, you're going to eat better, you're going to be happier, you're going to have better relationships. So all of these things are going to actually improve your overall health. So again, you know, the human body is complex, and we're complex, you know, spiritual, physical, psychological, physiological beings. So, trying to find that balance between all of those different ways of being human being are so important in our overall well being and health.

Peter Williams 44:32

I just think the other thing is it's such a, what's the word I look for? I mean, you know, I know males have some degree of andropause. And for some men, it's it's pretty horrific. But it's such a dramatic change in physiology for women is that, (massive) you know, I just come back and I was listening to that lecture and I think maybe it is that these women are ageing, you know, literally biologically the same. He has gone on and you know, that scientific group which, you know, they've, they're pretty solid. I mean, again, I was reading research at the weekend from a point of view of, you know, how they're looking at different, you know, we've certainly look at oestrogen as an anti ageing molecule and some of their glycan tests suggesting, you know, this woman actually on test, you know, we were seeing her glycans part of their immune system looking 20 years older. And I think about that across the board, because I can think about the exaggeration, you know, the sort of menopausal arthritic position. And look, you know, as I say, I'm not suggesting it's all oestrogen because you've had, you know, 50 years of, you know, working that skeletal system. So it's not going to get to 50 without any problems. But the amount of women that I see coming into me who, back pain, joint pain, you know, because we know oestrogen is incredibly protective on that, and it ties it beautifully with, I think you might be in perimenopause here based on the results we are seeing the complexity of it all. And I just think about this, and I sort of think about, I really do think that this is the time for women to actually spend a decent block of cash on themselves. Well, no, I'm being really serious about this. Because, you know, I think if we would be clear about this, is that the not? And this is absolutely not for me to dismiss what's happening conventionally, because for many people, it's almost I mean, I can think about my big sister in particular, you know, actually, she feels amazing, through a bit of progesterone and some oestrogen. But I think for other women, you know, that the capacity to actually say, you know, what, I need to spend a bit of money on myself and actually find what my next stage in life is going to be and how well I'm going to do that you've really got it sort of, the only way you really should do it correctly is is to get in front of an expert who can take it, number one, find out where do we stand currently? What's wrong? And how are we going to develop a programme going forward, and then be in that programme? Because I think this is I look at what I do. And I think we're similar in this is that, you know, and I look at the conventional side, and there are amazing people on both sides. The sad thing that saddens me about the conventional side is that well, it doesn't sadden me I think I mentioned this last time is how unbelievably brilliant they are, to get some degree of results in such a limited timeframe that you can't even you've got to understand, you've got what's going on. I know to be able to be able to build a programme that makes sense. And, obviously, we have the luxury to do that. So it's not that I think we're doing anything, I think that's a key important thing is that we have experts who are looking at people holistically, but also have the capacity to put them in a structure and tell them, Look, here's where we're at now, based off data. Here's what we're going to try. Let's give it a go. Let's see how you feel. And let's bring you back in and see whether we've got to make a different fit, or does this work? Or doesn't this work? And I think that's so, so important. It's so worth the money, Ghazala as well, that's what I like about this is that, you know, the reality is I don't think you're going to get that elsewhere. And you're going to be in you know, I suppose. And I know, a lot of people, you know, a lot of people can't afford it, but I just don't think you can put a figure on that. Because it's not that expensive. Once you know, the structure. Yeah,

Dr Ghazala Aziz-Scott 48:44

we say, you know, it's the price of a coffee out of a of a of a coffee is expensive these days, like you're like three pounds 50 a cup, but it's the cost of that basically, you know, and once we've sort of stabilised you, you know, and sort of, you know, we can mix several hormones into one preparation. I mean, also, I will I will often work with, you know, using regulated treatments as well as compounding. You know, if someone's really good on, you know, their oestrogen gel or a patch, and their Utrogestan you know, I'm quite happy to let them stay on that. And then I will just add in the testosterone and DHEA so, you know, I'm always thinking about the patient, you know, how to minimise their costs, how to make it the most convenient for them, and how to get the best results. Really

Peter Williams 49:33

How do we summarise this? Because obviously, we've had we've been very lucky to have you know, one at one of the key endocrine people in the UK doing this, how do we how do we summarise this? How would you summarise what would be the tips that you would give people

Dr Ghazala Aziz-Scott 49:48

and hormones are really important. You know, it's really important to recognise how important all of the sex hormones are in our general health, you know starting from puberty basically and going forward both men and women, and the important role they have in so many different aspects of our health, you know, our brain health, our cardiovascular health, our gut health, our immune system, everything is, you know, is governed by, you know, influenced by our Hormonal Health. And I think, really, really understanding the holistic principles behind having good Hormonal Health. So you know, when you're not needing hormone replacement, etc, etc, you know, important to have, you know, healthy lifestyle with nutrition that is a hormone balancing diet. So, a low glycemic index, Mediterranean style diet with lots of fruit and vegetables, lots of good fibre, you know, knowing understanding gut health, how do we keep our guts healthy? How do we minimise stress? How do we get a healthy work life balance? You know, what supplements do we need? You know, given that our quality of our food is not, you know, what it should be? How do we prevent endocrine disruptions and chemicals in the environment? So what can we do to optimise our hormone health, so that these are fundamentals? So I really want to emphasise and not just about expensive consultations and expensive compounding medications, you know, there's a foundation that we really need to make sure everyone understands. And then we can build on that, you know, and if those foundations are good, we minimise disease, you know, and that's another really important thing to understand. So, you know, first foundations are good, the amount of hormone treatments we need to give, and also, those hormone treatments are not going to be effective, unless we've got the foundations, you know. So that's also very important to understand. And, yeah, I mean, there's also so much now, you know, with with lots of, you know, Dr. Google, there's a lot of really useful information available online. But obviously, one needs to get it from reputable sources, you know, there's a lot of conflict of information as well on the internet, as well. So that can be quite confusing. But I think understanding the role of a good functional medicine practitioner, you know, good nutritional therapists, you know, they could do so much to get people into a better state of health. And it's not like we're expecting people to see, you know, these practices forever, but it's just being able to get them to a state of good health and helping them learn how they can continue this preventative way of living, is really, really important. You know, there's such an overlap between that and longevity.

Peter Williams 52:29

So I think what you're dead right, I think you've got to be practising the basics well, because if you practice the basics, well, then you get more out of your treatment, and you have to do less if we've got to apply medication on that side. So it's much more difficult to take the patient who

if we've got to apply medication on that side. So it's much more difficult to take the patient who isn't practising good health strategies, and then you don't know well, you know, is it the medication? Or is it the fact that they're just not doing what we need them to do on that one? Brilliant. So we will put your clinic, the Marian Gluck Clinic in the notes. So listen, I really appreciate the time, it's, it's been amazing to speak to someone that as I said to you, you know, my wife is my wife is currently going through it at the moment, and we really appreciate your help. And again, it's a it's not an easy trip for people. But I've seen enough on this now that it really is a time for women to who generally don't look after themselves. I think that's one of the other things, isn't it? Because they are the care provider for most people.

Dr Ghazala Aziz-Scott 53:35
Yeah, it's just that there's such a personality issue with women where they put themselves on the back burner.

Peter Williams 53:42

They become the caregiver. And of course, one of the biggest risk factors, but it really is a time and as I say that I've just seen I just see so much so so many of them struggle through this time and it's like look, but let's let's do it. Now let's get some time in are more and more convinced because just I think also the timing of things with regards to and certainly brain health, etc. And you know, the longevity side is that if you're definitely moving, if you feel as though there are signs of that perimenopause, it's time to go and get some advice. It's so crucial based on what we're seeing in the literature. And you know such a niceer second half, I think is the other thing on that side.

Dr Ghazala Aziz-Scott 54:24

AbsoluteIy mean, you know, given that, you know, we know women are living into their 80s and 90s. You know, if the average age of menopause is 51, we spend, you know, what, sometimes, but what I find really fascinating is that I must, there's a fantastic neuroscientist called Dr. Lisa Moscone. Probably hopefully people have heard of her and she's just written this book called The Menopause Brain. (Brilliant, yeah we like her work). Yeah, um, but what I think is really heartening as well, is that she says that that sort of brain changes that we see in the peri menopausal phrase for a lot of women, when they're four years after their last menstrual period, some of those changes do you know reverse. So it's also important to remember that our bodies are incredible. And that we do have adaptations, adaptive mechanisms that you know, can can support that. So, you know, for instance, having a more ketogenic diet in your perimenopause and menopause, for some women may really help their brain fog because, you know, ketones can cross the cell membrane in a brain cell where it's got low oestrogen, you know, glucose can't go across. So there's lots of ways our bodies do adapt to these changes, you know, if you know, so if you can't take HRT, you know, I think this is, you know, some of the things that have been negative about the sort of explosion in understanding about the menopause is that everyone thinks they absolutely have to take hormones. Well, it depends on the individual. And some people can't take hormones. And so, you know, there's so many other ways that we can support people, you know, to have better Hormonal Health, it's not always that we have to pump people full of hormones, you know, there are lots of things we can do. And the body also does a lot for itself, provided it's given the right tools.

Peter Williams 56:14

Give it a chance, which goes on to you've got to do the basics well, to give it any chance at all, because I'll listen, I really appreciate your time. You've been amazing on the last two podcasts. So thanks for that. And obviously, we'll link into into the Marion Gluck on the show notes. So thanks so much for your time.

Dr Ghazala Aziz-Scott 56:34 You're welcome.