Dr Louise Newson on progesterone sensitivity + hormone tests + GSM + HRT post cancer (and more!)

0:02Dr Sophie Shotter:Hi, I'm Sophie and this is Age Well with Dr Sophie Shotter, a space devoted to all things health, wellness and longevity. Because for me, ageing well is about looking and feeling like the best possible version of ourselves, inside as well as out. So together with my producer Fee, I'll be deep diving into the latest research, sifting fact from fiction. I'll also be talking to all kinds of trusted experts tapping into their knowledge, along with bringing you conversations from a range of interesting women and men, finding out how they age well. So this is my show. Welcome along. And as always, thank you so much for listening.

0:46Dr Sophie Shotter:Louise, I do want to first offer my huge congratulations. At the time of recording, you've very recently achieved the highest possible rating from the UK's health regulator. And I know you've had an incredibly challenging 18 months or so, which is a whole different podcast. But we couldn't let this wonderful news slip by. Well done. We're all really pleased for you. Oh, thank you. Yeah, it's a great team effort and it's a reflection of lots of people's hard work. But the service that we give to women, which I'm very proud. Thank you. I know you're also the UK's leading voice on women and menopause so it's terrific to have you on the show naturally we want to talk all things hormones and when I talk to patients and we have conversations about hormones and perimenopause I'm often asked what the perfect levels are i.e the so-called ideal progesterone number optimal estrogen range basically that exact ratio that women need for balance.

1:40Dr Sophie Shotter:But as far as I'm aware and concerned, there isn't one universal set of agreed numbers because every woman is so different and every woman's hormones operate within context. So that may be age or phase they're at in cycles, stress levels, all kinds of different things, even potentially hormone receptor sensitivity. As far as I'm aware, two women can have the exact same estradiol value on a lab report but both feel completely different so could you explain to listeners why hormone activity isn't just determined by a blood test and why it's important to actually cross-reference and talk to a woman about how she actually feels.

2:19Yeah there's lots to unpick there but it's a great question actually and it's good timing because I've just been talking to one of the managers of the labs we use to unpick even more of this because it gets worse the more you know actually. So the first thing is, as you'll agree, I hope, in medicine we individualize care. And for me the most important thing about being a doctor is listening to our patients. And I was taught many years ago in the 80s and 90s when I was a medical student is that the diagnosis is in the history. You take a good enough history so you have a storytelling from the patient, you will get the diagnosis.

2:53And so that is really important. Medicine is still an art as well as a science. And so any test in medicine, whether it's a, you know, a scan or a blood test or whatever, helps us to support that diagnosis usually rather than make the diagnosis. So that's the first thing with anything in medicine. Now, as you say, we can do hormone blood tests. I often do, and I do blood tests, but I do estrel and testosterone levels. Progesterone levels really vary so much. I never actually do them. I don't find them useful. But if we think for a minute, when I do a blood test, I'm seeing what's in the blood at that time.

3:30It doesn't tell me what's in the tissues, what's in the brain, what's in other areas of the body. And it's a snapshot. But we also know that our hormones can really vary. So if or when I was perimenopausal 11 years ago or so, my hormones were really fluctuating. So I could have had a really low level one time of the day or a really high level the other time of the day. And that's just the way my body's responding. And so in medicine, you want to put any blood test in context with what else is going on in the patient. And we've all seen it where you have a blood test and you think that doesn't quite match.

4:03And so then we might repeat the blood test or might think, well, what else is going on? and so that's another thing to consider and then the other thing is like you say what is normal and actually we don't really know what normal is because when you look at the normal reference ranges for women they're actually based on a punishingly small number of women who we don't even know were healthy or not so it's actually quite shocking we know with estradiol levels we tend to work for the range to be about 250 to a thousand but some people feel a lot better when their level's more like 600, others feel fine when it's 251.

4:42But again, I don't work to a number, I work to symptomatic improvement, but also looking at, you know, what their level is, thinking about future health as well. Testosterone is a whole new sort of ballgame, really very different, because when we look at the studies that they actually base normal so-called levels on, it's actually looking at a banishingly small number of women. In fact, 71 aging women is what they have based normal ranges on for women. And even in the lab notes, it says apparently healthy women. So I'm sort of saying this because I think it's really important that people realize that it's absolutely impossible to know what is normal for one person and another.

5:29but blood tests like I say are a guide.

5:32Dr Sophie Shotter:Could we also talk about this idea of detox pathways and perhaps the fact that a woman's hormones are active not only in her blood but inside her tissues. I mean we know that estrogen is an estrogen receptors are found throughout the body including the brain, the bones, the gut, the skin. Do some women have particularly sensitive estrogen receptors in certain parts of the body? So it could be that she may have low levels of estrogen in her blood but experiencing high estrogen activity elsewhere or vice versa and is it the case that some women's bodies don't detoxify or flush out her hormones as efficiently as ideally she maybe should especially if she has a sluggish metabolism or thyroid issues or if other hormones are disproportionately elevated yeah it's a great question and obviously it really varies and i think the first thing to answer is we have to be really clear what we're talking about with estrogen and it causes no end of confusion to doctors and often to women as well because we make different types of estrogen as women naturally in our body so we have estradiol, estrone, estriol and there's also ethanol estradiol which is the synthetic estrogen that's in all bar one combined oral contraceptive which has a really strong affinity for the receptor and is metabolically completely different to estradiol of course because it's got an ethanol ring on it And our oestradiol and oestrone work very differently.

6:57Oestrone is very pro-inflammatory, oestradiol is very anti-inflammatory. And so we've got different oestrogen receptors as well. So it depends on the binding to them, but it also depends what else is around in the body because you can get some other hormones that can partially bind the receptors. And like you say, our hormones are in balance with other hormones, especially our thyroid hormone but also insulin other metabolic hormones but the other thing is our hormones are produced in different tissues everyone thinks they're just ovarian hormones and we know obviously they're made in the adrenal glands but they are made in the brain as well but we've also got enzymes that convert our hormones to other hormones in our tissues for example we've got aromatase all around our bodies including our brains that will aromatase testosterone to estrogen and estrogen as well so it's a balance of those really can make a difference and the detoxification pathways in my mind sound really scary they sound like my hormones are so dangerous that they've got to get rid of them as quickly as possible and I'm not sure they actually are that dangerous and so I worry about that I know that people talk about how to flush the system and everything but I think some of this is confusion with ethanol estradiol which I really don't prescribe now i know how it works in the body but that can really build up especially in

8:20Dr Sophie Shotter:the liver and that is a concern and as you're talking i'm thinking about another podcast episode we did to do with genetic testing and the so-called gary brager test and the mthfr mutation and are we methylating and maybe it's that and you just go down these rabbit holes just oh um now that we've had or are still having this so-called menopause revolution i feel quite silly saying this but One of the things that I hadn't realized initially years ago, pre-menopause, I'm now post-menopause, was that blood tests only offer a snapshot of hormones in time. You've obviously said this earlier. I just didn't know this years ago.

8:55Dr Sophie Shotter:Can you explain the lifespan of some of these hormones that we all talk about? Things like cortisol, for example, because I've heard that this follows a circadian rhythm or that progesterone shifts throughout a woman's cycle. And estrogen, I think, rises and falls. Or maybe because we have different estrogen, maybe that's different. And testosterone, I've heard, can be influenced by things like sleep and stress. I mean, they all have their own life cycles, do they? So the three main hormones, progesterone, estrogen and testosterone, don't work in isolation. And I think that's what so many people don't realize.

9:26They think they're just ovarian hormones that affect our periods. And of course, they do a lot more than that, but they work with all our other hormones. So they work with, you know, they work with adrenaline, they work with cortisol, They work with our incident, but they also work in our brain as neurotransmitters. So they can affect the levels of other neurotransmitters like dopamine and serotonin and melatonin. So it's really important when we think in the bigger picture. But when we think about stress and hormones, we have to remember that progesterone helps balance our cortisol and our cortisol is our main stress hormone.

10:03So a lot of people who have a lot of cortisol in their body have low progesterone, actually. And we know that progesterone receptors work better when there is less stress and less adrenaline in the system too. And also if our sugar levels are regulated, then progesterone will work too as well. Our hormones are always fluctuating just because that's the way they are. All our hormones in our body change. And throughout the menstrual cycle, it's really important that you ask that because we get a shift, especially in progesterone in the luteal phase, the second half of a woman's cycle, she actually gets very high progesterone levels and then they drop very quickly, usually just before a period.

10:47And that decline can trigger symptoms. And those symptoms can be the same as perimenopausal or menopausal symptoms. And so a lot of women have PMS, premenstrual syndrome, and a significant number of women have PMDD, premenstrual dysphoric disorder. And it's very important that these women are picked up so they are considered for hormones rather than antidepressants, which is what they normally are prescribed.

11:10Dr Sophie Shotter:Yeah, I hear that so often that women are just being prescribed antidepressants. The other thing that I talk to my patients about is that hormones don't operate in isolation. They're all an interconnected system and they're constantly influencing one another. So estrogen dominance, as I understand it, for example, can suppress the thyroid and therefore metabolism. Low progesterone can increase sensitivity to cortisol and amplify a stress response, etc, etc. In other words, when one hormone is off, the ripple effects are rarely confined to just that pathway, which again is why focusing on a single blood test without considering this more holistic view of the body can be tricky.

11:51Dr Sophie Shotter:What are your thoughts on all of this? And do you ever do more extensive tests on a woman? and do you have any particularly interesting obviously anonymized case studies that you can share? Yeah it's so important actually and you know I don't want to big myself up as a GP and physician but I do feel as a chief and a general physician you know I'm a lot more placed to looking after women with hormonal issues than perhaps gynecologists who tend to not have any medical training at all beyond medical school because we have to think about the body as a whole, otherwise you're missing out. I'm very conscious that my clinic is private and the cost, but a couple of years ago, we managed to get the prices down a lot of our blood tests.

12:33So most patients actually, we offer it to women, have more extensive blood tests so we can look at their thyroid, their vitamin D, their ferritin. And that's really important actually, when we're trying to look very holistically, like there's no point me saying, oh, you're tired because you've got low testosterone and then find that they've got really low ferritin or they've got an underactive thyroid gland. So we have to look at everything. And I think that's crucially important. We also know that, you know, when our hormones are balanced, it's then a lot easier to look at lifestyle, to look at nutrition, to look at exercise, to look at sleep, look at other things that are going on in that woman's life.

13:10And all of those will have a usually positive effect on hormone balance as well. So it worries me that people just go and have a hormone blood test and then, you know, get hormones online. And then no one's thinking beyond that. And I think that's crucially important that we don't just see this as a isolated, let's just give a hormone and see what happens. The thing about estrogen so-called dominance also worries me because actually it's usually, we know that hormones fluctuate and we've got levels of very high in some women, but then when we repeat them, they're often normal or very low because the hormones can really swing.

13:45and a lot of people find actually that it's their progesterone that starts to decline quicker than estradiol and so a lot of people have low progesterone quite a lot have low testosterone before estradiol declines at all and because at medical school we're always taught you give estrogen first if they have a womb you give progesterone and only if they've got really reduced libido do you consider testosterone and that's the way people often prescribe which actually I don't really agree with because it doesn't match physiology and the changes that often occur in women.

14:17Dr Sophie Shotter:Yeah, that's so useful. And again, it's making so much sense. Okay, speaking of progesterone, can we hone in on progesterone? Because I am suddenly reading a lot about progesterone intolerance or sensitivity. Maybe it's the algorithm on my Instagram or whatever I'm looking at. What is this? What are the symptoms and what are the solutions? And can you maybe just give us a little explainer? Yeah, so I have done a YouTube about progesterone intolerance. It's where, you know, people listen to us, they want more information. But first of have to be really careful with our language, what we mean about progesterone, because when I talk about progesterone, I'm talking about the progesterone either that we produce ourselves as women when we're younger, or the progesterone that I prescribe, which is a body identical replica.

14:59So we know the molecular structure. It's exactly the same. So the body doesn't know the difference because it fits onto the receptor the same way. A lot of people use the term progesterone when they're actually talking about a progesterone or a progestin if they're in the US, which basically means it's a synthetic chemically altered substance made to be like progesterone and it's usually as a contraceptive but it's not the same so a lot of people have progestogen sensitivity and intolerance so a lot of the people have mental health issues they maybe start a progestogen in a progestogen only pill or a combined oral contraceptive or they might have something like a marina coil or an implant and they feel their mood dip they feel terrible they might feel bloated, they might have skin changes, hair changes, and they remove or stop the contraception and they feel fine again.

15:49So that is a progesterone intolerance and it's very, very common actually. And I'm not surprised because it doesn't affect the receptor in the same way. And actually it can block the receptor so you don't have any beneficial effects of any progesterone your body might be making at the same time. Some people say that even when they have, for example all micronized progesterone that they have side effects with it and when we have anything orally in our body it gets metabolized through a liver and broken down to other substances so some people are intolerant or they have side effects if you like to the metabolites of the micronized progesterone or it might be something like a preservative or another substance in the capsule rather than the actual progesterone increasingly in our clinic we prescribe quite a lot of phanxagest which is pure progesterone that can be given as a pessary or suppository so it can be used vaginally or rectally and we can give it at higher doses and we often find that people who don't tolerate lower doses of oral progesterone actually often transform they don't just feel better they feel wonderful with a higher dose of a suppository or pessary because it can get into the bloodstream at a lot higher dose and then get into the whole body so there's always options but we have to really firstly work out what someone means when they talk about progesterone intolerance.

17:09Dr Sophie Shotter:And we'll link into your YouTube explainer as well on the show notes. So thank you for that. I don't know about you, but I've noticed this slight progesterone backlash. I know a lot of women rely really heavily on it for their sleep. And many women are thrilled with all the positive impacts. But I've also seen a few people now talking about an over-reliance on it. and I heard one doctor say that progesterone also works on the GABA receptors in the brain but if we have too much then over time our GABA receptor sensitivity changes meaning we need more progesterone to have the same effect. I've also noticed that some people say estrogen is better as an architect of sleep because it does things that progesterone can't so keeping our core body temperature regulated, maintaining serotonin so it reduces hot flashes and night sweats that wake many women up.

18:00Dr Sophie Shotter:What do you think of this whole progesterone backlash? So I think one of the things is we don't have huge evidence because no one's done the right studies on women, but we have a lot of basic physiology. I've got a pathology degree as well, so I'm very interested in basic science and I'm very interested in neurophysiology. So one of the things is that most people, including myself, have been forgetting progesterone for many, many years and now we're talking about it. It's like anything, there's always people out there to shoot others down and I don't really understand why. People talking about it being addictive, I find really insulting actually because you can't really be addicted to something that's good for you.

18:42I mean, I get up every morning and do yoga, so you could say I'm addicted to yoga, but I don't know that's a bad thing to be addicted to. You know, I don't get up and have a gin and tonic every morning, which would be an addiction problem. So I think we have to be careful with our language as well. There's nothing wrong with stimulating GABA. The other thing is I've written quite a lot about the role of progesterone and the estrogen and testosterone in my book that's coming out in May. And progesterone is, like I said, it's the key hormone. If you're going to have one, you might as well have progesterone because I've already said it forms our other hormones.

19:15It forms the estrogen and testosterone. But it is actually very anti-inflammatory in the body and the brain. it stimulates our pain receptors so it can modulate our pain response it can help with sleep it can help like i say with cortisol it can help with mood and be very calming and one of the things is i think it's really sad that if someone's had a hysterectomy they're told they don't need progesterone well they don't need it for their womb but what about the rest of their body and just because the guidelines say that the guidelines are not based on basic physiology or patient choice as well.

19:49You know, I have a lot of patients who have progesterone and they might have a Mirena coil in, but the Mirena coil is not going to stimulate their progesterone receptors. And we know also there are lots of beneficial effects to the brain with having progesterone. And there's some evidence that women have progesterone, have a lower instance of breast cancer and other inflammatory conditions. So it's important not to forget it, how important progesterone is. And I'm also quite intrigued that so many people seem so worried about it, but these doctors also probably prescribe synthetic progestogens, which we know have established risks with them.

20:28Dr Sophie Shotter:Thank you so much. I think we've really unpacked some things around progesterone that a lot of people, as you say, don't realise and things that even I hadn't realised. Louise, this is kind of a personal question, as in my personal life, but it's actually on behalf of the tens of thousands in the UK alone of women post breast cancer. I'm two years clear of a hormonal driven breast cancer. I'm no longer taking HRT. So I'm flying solo with all of these symptoms. I really miss my HRT. The most debilitating system that I have, I've actually been okay with metaphors. I'm very fortunate. But the debilitating symptom that I have is incredibly painful vaginal dryness and recurrent UTIs.

21:06Dr Sophie Shotter:And the pain is one that I can't re-describe to you, but I'm sure that you must hear in clinic all the time. I sometimes can't work with the pain. I haven't taken the aromatase inhibitors I was offered post-treatment because for me, I didn't feel the side effects warranted the data. I have a strong family history of osteoporosis along with womb cancer. So I chose no. Despite explaining all of this debilitating pain, my GP is uncomfortable prescribing me anything stronger than the very weakest possible local vaginal HRT, especially because I'm not on tamoxifen or aromatase inhibitors. So I've been refused the external 0.1 % estriol and offered the 0.01%, which is obviously 10 times weaker.

21:51Dr Sophie Shotter:I've also been refused all estrid, now this is where I get confused, all estridial vaginal products, including my beloved Vagifem, which they were prescribing when they stopped. And I've been asked to use the much weaker strength estriol products. I feel it's been worth me self-advocating in order to have ongoing quality of life which I could talk about for a long time but won't what I've been advised to do on forums by many women is to lie on an online pharmacy about my medical history and pay for the products that I feel I need I have done this Louise because the pain was so awful many other women with a similar history do this and a lot of women are talking about this on the forums obviously I have financial privilege that I'm able to do this.

22:34Dr Sophie Shotter:What would you say to the tens of thousands of women in the UK post breast cancer who are looking at our sisters who are going, it's a revolution going, it's amazing you're doing this, but we're kind of jealous and we kind of feel we're missing out and we're being refused this localised HRT or being given minimal. Where is the latest evidence at? And also what happens when a patient reluctantly goes head to head with her GP in a bid to self-advocate and take agency? sorry that's a really long question it's not I feel a mixture of silent angry and frustrated listening to you and there's a lot to unpick and I'll try and keep it simple but please ask questions as well firstly estrogen receptor positive breast cancers aren't hormone driven they have receptors on them and I've already said our hormones work all over our body so we have receptors on every cell in our body and estrogen receptor positive breast cancer they're the same when it's estrogen receptor negative it just means the cancer's mutated and lost the receptor status so a lot of women are told their cancer has been caused by estrogen and what we do know actually is that when women have estrogen only HRT they have a lower incidence of breast cancer so that's just to reassure people there's lots of reasons why people get cancer and some of it is known some of it's not known as often a multi-hit process.

23:58And so it's not usually related to our own hormones causing cancer, because that just wouldn't make sense. We do know, for example, the synthetic contraceptives are associated with a small increased risk of breast cancer, but that's not the same as the hormones we prescribe. One of the big problems is we don't have any data. We don't have any good quality data to say hormones are safe or not safe after breast cancer. But actually, we do have the small studies we have actually seen that it's positive. We also know if we start with vaginal symptoms, we know around 80-85 % of women have symptoms related to genital urinary syndrome of menopause.

24:40And you're describing some of them and they often don't improve with time. So it's really important. We know about 30 % of all sepsis is due to urinary tract infections, urosepsis. And, you know, we should be doing everything we can do as clinicians to reduce that and also reduce harm to our patients. The evidence is very clear that localized hormones don't get absorbed into the body. And so this whole, I don't know if I'm allowed to swear on this podcast, but the bullshit of you being told you can or can't have a certain dose is just ridiculous, actually. We know the American Urological Association guidelines have recently updated and shown that there is enough evidence to say that vaginal preparations are beneficial for women who've had breast cancer.

25:31Over here in the UK, people seem to be a bit more cautious because it's led by often the British Menopause Society who aren't regulatory at all, but they've said people need to speak to an oncologist and have some written discussion, which is not feasibly possible for most of us when there's so many women who've had breast cancer. But we've got the data, we've got evidence and we've got common sense as well. I often use prasterone actually for my patients who have breast cancer. So prasterone is DHEA and it converts to both oestrogen and testosterone because we've got a lot of androgen receptors in our perineum and our genital urinary system and tracts and it can be transformational.

26:07So it's called prasterone. The other name is intrarosa and it's a daily peserone.

26:13Dr Sophie Shotter:Yeah, sorry to interrupt you. I've actually lied on a form, or just someone is upstairs as we speak. Yeah, if someone's on an aromatase inhibitor, I would still prescribe Crasterone. And I feel really people should be taking it almost as soon as. They shouldn't be waiting for symptoms to be very severe. And then some people need to use a topical Easter diet or Easter aisle, doesn't matter what strength, cream or gel to use externally as well. So that's very simple, actually. Would you say to use the DHEA daily, the pessaries daily? Yeah, absolutely. Yeah, yeah. I would definitely use them daily.

26:49And then if you need to use anything else externally, I would use that as well. And I wouldn't worry about it. And yeah, it can be used in the long term forever as well. And like I say, the dose is incredibly low. and we also know that we when we look at systemic hormones I've already said there are three hormones oestrogen progesterone testosterone and so we don't always have to go to oestrogen when we're giving HRT and increasingly in the clinic I'll start someone on testosterone first because testosterone is an independent hormone and a lot of women find their symptoms really improve with testosterone and then you don't have that whole estrogen sort of worry conversation and then progesterone as well.

27:35Dr Sophie Shotter:Sorry I had heard that you can't have testosterone if you're not having estrogen because it will just convert into estrogen. Well yeah no people think it all aromatases into estradiol but it doesn't actually and actually when we look at our patients who are on testosterone and we do their estradiol levels as well we don't get a rise in estradiol so So that's a theoretical thing. But actually, we have to remember that our bodies make estradiol. You know, you can block estradiol by having an aromatase inhibitor. Even if you have your ovaries taken out, you still produce it in your other tissues and brains.