ZOE Science & Nutrition - HRT for menopause: is it safe?

Episode Date: May 11, 2023

Menopause is a time of significant hormonal changes which can lead to a range of symptoms that can severely impact quality of life for many women. So, a drug that promises to reduce these symptoms is ...incredibly welcome, but it has been steeped in controversy. HRT (Hormone replacement therapy) has been widely debated, with conflicting information about its effectiveness, with some suggesting HRT is outright dangerous. In fact, a massive study twenty years ago linked it to an increased risk of breast cancer. As a result, the numbers of women taking HRT plummeted. So should HRT be avoided at all costs?  In today’s episode, Jonathan is joined by the author of that very study and esteemed Professor JoAnn Manson, alongside Dr. Sarah Berry to explore the science behind HRT. Professor JoAnn Manson is a professor of epidemiology at the Harvard School of Public Health and one of the world's most experts on HRT and menopause having run multiple enormous studies to uncover the effects of hormone replacement therapy on women’s health. With the help of ZOE regular Dr. Sarah Berry, they delve into the science behind HRT, empowering listeners to make informed decisions about treatment for symptoms of the menopause. Download our FREE guide — Top 10 Tips to Live Healthier: https://zoe.com/freeguide Timecodes: 00:00 Introduction 00:12 Jonathan's introduction 01:33 Quick Fire Questions 03:27 What is the menopause? 04:10 What is the perimenopause? 05:46 What is the state of the current conversation on the menopause? 07:13 Should women seek help about the menopause? 07:58 Why do some women have symptoms and others not? 09:15 Yougov and ZOE study results on the menopause 11:35 Why is the menopause getting more attention now? 13:39 Should we be taking these symptoms seriously? 17:10 What else can be done asides from HRT? 18:49 Studies on the relationship between diet and menopause symptoms 19:35 What can help alleviate symptoms? 21:23 Are there any specific foods that can help improve symptoms? 23:37 Are menopause specific supplements effective? 24:50 How does HRT work? 26:26 Is HRT just oestrogen? 30:59 Does testosterone have a use for menopause? 31:58 What is the controversy behind HRT? 35:56 What's the latest advice and health risks? 38:11 When should you stop hormone therapy? 40:43 Do symptoms persist when you come off of hormone therapy? 42:00 How long does HRT take to start working? 43:07 How does HRT affect weight management? 45:15 Summary 48:04 Goodbyes 48:25 Outro Check the trials mentioned in today’s episode:  MsFlash: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731298/ ZOE Menopause Study: https://joinzoe.com/learn/menopause-metabolism-study PEPI Trial: https://pubmed.ncbi.nlm.nih.gov/7807658/ Follow Sarah: https://twitter.com/saraheeberry Follow ZOE on Instagram: https://www.instagram.com/zoe/ Episode transcripts are available here. Is there a nutrition topic you’d like us to cover? Get in touch and we’ll do our best to cover it.

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Starting point is 00:00:00 Welcome to ZOE Science and Nutrition, where world-leading scientists explain how their research can improve your health. Menopause is a condition that affects almost every woman. Symptoms can include hot flashes, disturbed sleep, even brain fog, and can severely impact quality of life. It's no surprise then that the treatment, hormone replacement therapy, or HRT, is incredibly welcome. But this is a controversial treatment, and information about it is confusing. Some suggest HRT is dangerous. In fact, a massive study 20 years ago linked it to an increased risk of breast cancer. And as a result,
Starting point is 00:00:45 the number of women taking HRT plummeted. So should HRT be avoided at all costs? Well, according to the author of that very study, Joanne Manson, no. In fact, quite the opposite. Are you confused yet? Luckily, Joanne joins us today to get to the bottom of all this. She's a professor of medicine and epidemiology at the Harvard School of Public Health and one of the world's foremost experts on HRT and menopause. Joanne and Sarah, thank you for joining me today. Great to be here. Great to be back, Jonathan.
Starting point is 00:01:24 Wonderful. Well, look, why don't we, as always, start with a quick fire round of questions from our listeners. And we had a lot of questions on this topic. And Joanne, you may remember the rules are really tough and today we're going to keep them extra tough. So we want you to say yes, no, or maybe if you can't do a yes or a no. Are you willing to give it a go? Yep. no or maybe if you can't do a yes or a no are you are you willing to give it a go yep fantastic all right so start at the beginning menopause is getting a lot of press at the moment having previously been almost never mentioned have we been too slow to take it seriously yes wonderful i'm glad you said that otherwise the rest of the podcast is going to be a bit flat
Starting point is 00:02:03 so that's good i love that there was no hesitation there whatsoever. That one was easy. There we go. We're just like lulling you into a false sense of security. No, not really. Next one. Do most women experience symptoms during menopause? Yes. Should most women consider medication like HRT when going through menopause? Yes. Should most women consider medication like HRT when going through menopause? No. Very interesting. Is HRT safe for most people? Yes, with some qualifications, which we'll get into. Brilliant. I was going to follow on. is HRT safe for everyone? No. Can HRT prevent menopause weight gain? No.
Starting point is 00:02:53 I have stopped having periods. This is a question from one of our listeners. I've stopped having periods but never had menopause symptoms. Should I consider taking HRT? No. Wonderful. I think it's going to be quite controversial, which is going to be lots of fun. And finally, and you can have a whole sentence now, Joanne,
Starting point is 00:03:09 because we have this question from lots of people. What's the biggest myth that you hear about HRT? I think the biggest myth is that women who do have bothersome symptoms should just suffer through these symptoms because there's no help available for them. So Joanne, let's start right at the beginning, just in simple terms. What's the menopause and the perimenopause? When does it happen? And I guess most importantly, what impact does it have on women's lives? So the menopause means the end of menstrual periods. It's usually defined as 12 months without menstrual periods because of the loss of the ovaries functioning and production of estrogen reduction in estrogen levels and the follicles in the ovaries are no longer functioning. So you stop having menstrual
Starting point is 00:04:05 cycles. This usually begins average age is 51. The perimenopause is defined as the time period when menstrual periods become irregular. This is often several years, five years, six years, even longer before the final menstrual period. And some women will begin to have hot flashes, night sweats, beginning during that perimenopausal period. The perimenopause ends one year after the final menstrual period. It ends at the time of menopause, meaning one year after the final menstrual period. This is a very impactful event in a woman's life, the transition from the premenopausal years to the perimenopause and the menopause postmenopause. And Joanne, one of the things I'm really struck about is this shift in talking about the menopause, post-menopause. And Joanne, one of the things I'm really struck about is this shift in talking about the menopause.
Starting point is 00:05:08 So I think about my mother going through this and she didn't say a word about it. And it was definitely one of these things that was sort of completely taboo. Certainly as a man, it was completely taboo, but speaking to lots of my friends and my sisters, this was actually pretty taboo just in general. lots of my friends and my sisters, this was actually pretty taboo just in general. And I think you said quite strongly, really, that it needs to
Starting point is 00:05:29 be very different today. Well, it's so important that women do seek help for these symptoms. In the past, the pendulum has swung very widely. And it used to be in the 1980s, 1990s, women were being started on hormone therapy almost routinely in some countries, very frequently in the United States. Whether or not they had menopausal symptoms, they were being started on hormone therapy primarily for prevention purposes, prevention of heart disease, prevention of cognitive decline. There was a perception that hormones could help women stay young. The pendulum then following the Women's Health Initiative results, there was a very wide swing to hormone therapy is bad for all women. All women should stop hormones, their pills and
Starting point is 00:06:27 patches. No women should take hormone therapy. In the past 15 years or so, 10 to 15 years, the pendulum has started to rest in a more appropriate place, which is that hormone therapy is appropriate for some, but not all women. And the best candidates are women with moderate to severe or bothersome hot flashes, night sweats, and other menopausal symptoms. And they should seek help for decision-making about hormone therapy or non-hormonal treatments. That's really interesting. So I guess the way you're describing this, I think it's something we'd really like to talk more about how the science has sort of played into the shift in this pendulum. I guess one question before we start to switch towards HR2 is maybe just thinking about the
Starting point is 00:07:18 menopause itself. Do we understand why you're describing some women are going through this with no or very few symptoms and other people, you know, I've certainly heard like severe enough symptoms that people say, you know, I need to give up my job or like really drastic changes. Do we, do you understand what's going on there? There have been studies looking at risk factors for having symptoms and some risk factors have been identified. There are some racial ethnic differences. There are also some differences. Women who are smokers or who have higher body mass index do tend to have more frequent symptoms.
Starting point is 00:07:59 Women who have more comorbidities, such as high blood pressure and some of those health conditions may be more likely to have these symptoms. Also, stress, having a stressful life, stressful environment predisposes to having hot flashes and night sweats. So there are racial, ethnic, cultural differences. For example, in Asian countries, it's much less likely to report hot flashes, night sweats. There are a number of risk factors, but they're not that predictive. In general, it is very, very difficult to know until you experience that whether or not you are going to have the bothersome symptoms. I think, Jonathan, to add to what Joanne has said is there was a recent
Starting point is 00:08:45 poll in the UK. We often do these polls called these YouGov polls, Joanne, and it looked at several thousand peri- and postmenopausal women and asked them just how burdensome the menopause transition and postmenopausal phase was for them. And what they found is that one in 10 people actually said they had to leave their job because the symptoms were so burdensome. And I found that shocking. And I found that shocking despite the fact that we've also done a huge survey ourselves at ZOE from the ZOE Health Studies, looking at the prevalence of symptoms. And Jonathan, despite being a female and despite thinking that I'm quite clued up on all of this, because I know we've published research in this area, I was actually shocked just how prevalent
Starting point is 00:09:31 some of the symptoms were. And so we saw, for example, in a cohort of, this was about 8,000 perimenopausal women responding to our ZOE health study survey that 81% of people reported sleep disturbances, 65% of people said they'd experienced some sort of anxiety, 68% of people brain fog, you know, 63% hot flushes, which we often talk about and huge proportions reporting other symptoms such as joint pain, weight gain, memory loss. And this is really high. And I'm quite fascinated by some of the data, Joanne, that you've just talked about, that 75% of people report symptoms, but that potentially only 20 to 25% say that they're really burdensome. And I'm curious where some of that data comes from. I think it's very subjective whether the symptoms are considered bothersome and burdensome enough
Starting point is 00:10:32 to start treatment. Many women do not want to be on a medication for their symptoms, and they do feel that they can try to avoid triggers. We know there are some triggers for hot flashes and night sweats. And these include spicy foods, warm beverages, alcohol, being obviously in a warm room, warm temperatures will bring this on. And emotional stress is a major trigger for hot flashes and night sweats. And one of the reasons I wonder why the menopause is getting a lot more attention, beside the fact that we have loads of influencers in the UK and the US active on social media around this, is that over the last 30 years, the female workforce has increased dramatically. And given
Starting point is 00:11:22 that statistic that one in 10 females are having to leave their job because of menopause and because it's also the symptoms are impacting productivity, decision-making, et cetera, it's all been reported from this survey. I wonder whether now that it's affecting the economy, that's why more is being done on this. That's very, very possible. But I do think that the advocacy of the patient population the activism and advocacy of the population make a tremendous difference in terms of the amount of attention given to a health condition and i i think that there is fortunately increasing attention because women are noticing that this is a neglected topic. This is something that really is affecting their quality of life, a very large percentage of the population, affecting their work productivity, affecting their health.
Starting point is 00:12:20 I mean, we're not talking about only quote-unquote quality of life issues. When people are having symptoms like this that disrupt sleep and are affecting day-to-day activities and causing stress, this affects health and plays a role in terms of some of the metabolic problems that so often occur during the menopause, including weight gain, higher risk of abnormal cholesterol, abnormal blood pressure, diabetes. These all are playing into a higher risk of these cardiometabolic conditions, as we call them. As Zoe's chief scientist, I wanted to talk about something that's not talked about, menopause symptoms. Over half of people on the planet experience perimenopause and menopause, yet symptoms are often misunderstood or dismissed. Zoe's new
Starting point is 00:13:19 Menoscale calculator lets you score your menopause symptoms. Your Menoscale score may help you make sense of what you're experiencing. Personally, as a woman experiencing perimenopause, it's a key talking point with my friends. And now we have a score that we can share with each other. To me, this calculator is a game changer. At Zoe, we're moving menopause research forward. We recently conducted the largest research analysis of menopause and nutrition in the world. In our research, participants reported an overwhelming number of symptoms. 66% of perimenopausal women reported experiencing over 12 symptoms, like weight gain, memory problems and fatigue.
Starting point is 00:14:01 The good news is our research shows that changing our food habits may reduce the chance of having a particular menopause symptom by up to 37% for some women. The Menoscale calculator puts our science in your hands. Go to zoe.com forward slash Menoscale to get your score. The calculator is free and only takes a couple of minutes. As we scientists say, if you can't measure it, you can't change it. All right, back to the show. I still find this thing sort of rather extraordinary that, like for so long, nobody has really talked about it,
Starting point is 00:14:36 that even now it's not as well understood as I feel it should be. If I think about, I don't know, imagine how well everybody understands pregnancy and childbirth and having small children. And this is such a big topic of conversation and the level of symptoms. I'm still struck when you say this that, I mean, even the mild symptoms sound really bad. It does feel as though there's almost like a different benchmark for this than there are for many other things. And that even listening to you describe this, it feels like you've been a bit tough to me. I feel like if I was coming in with those symptoms for something else, you wouldn't
Starting point is 00:15:16 be expecting to shrug them off. You'd be expecting to level, of course, you need to go and make a whole bunch of changes for them. Do we sort of tolerate this more just because this is a sort of inevitable life change? You should just put up with it. And are we even now maybe not treating the same way as we would as other things? Or is that a wrong way to think about it? I think it's very important that we take these symptoms seriously and not shrug them off. And in fact, not expect that women are going to be suffering with these symptoms if they
Starting point is 00:15:53 are interfering with their quality of life, disrupting sleep, or having any of the adverse impacts on their life. I think the issue is more that all medications do have some risks, and it will come down to a benefit-risk balance in terms of whether the symptoms are severe enough and the benefits that women are likely to get from treatment will outweigh the risk of taking hormone therapy or antidepressant medications, some of the non-hormonal medications, which also have some risk. All women with these symptoms should think about the triggers, try to avoid triggers whenever possible, and increasing physical activity can be helpful for some women. And some of these approaches that are virtually free of any downside. But I think as with any medication in, you know, clinical medicine, we have to be very careful about weighing benefits and risks. This is the decision-making process. And I don't think we
Starting point is 00:17:06 should go back to recommending hormone therapy for every woman as she traverses menopause, because that would then be putting 75% of women on hormone therapy. And there are some risks of hormone therapy, although overall, in a woman who is having bothersome symptoms and is in early menopause and generally good health, as is the case for most women in early menopause, the benefits of estrogen therapy, menopausal hormone therapy will likely outweigh the risk. And Joanne, before we move on to talk in more detail about HRT, I'd love to pause for a moment and put it into the context of what else can be done, given that at the moment we have some very
Starting point is 00:17:59 strong advocates out there for HRT is the answer to everything. And I know this is something you've done some research in, and I'd like to just share with you some results of some really new data that we've got again from our ZOE Health Studies and see how it compares with some of the clinical trial work you've done from the Women Health Initiative. So we asked perimenopausal women questions about their weight, and we also asked them questions about their diet as well as their symptoms. And what we found was that there was an association between the weight of the individual and the number of symptoms and the severity of symptoms. So for example, we found that if people were overweight, they had about an 80% higher chance
Starting point is 00:18:46 of having brain fog or headaches. They had about 60% greater chance of having a depression or low mood and around a 40% greater chance of having hot flushes. And then what we also found was if we then factored in diet and we separated out women according to the quality of their diet, that actually this resulted in significant changes in their chances of having these symptoms. So what we found was that people that had a very high quality diet had about 30% lower risk of hot flushes and sleep disturbances, a 20% lower risk of brain fog and anxiety. Now, this is what we call, Jonathan, cross-sectional data. So this was data that we collected in one point in time. But
Starting point is 00:19:33 I know, Joanne, you've actually carried out a study where you've modified people's diets, followed them for a period of time, and then seen how this impacts their symptoms. And I'd love to hear a little bit more about that. There was a study called Ms. Flash that looked at a number of interventions, including omega-3 fatty acids, the fish oil. This was not found to be effective in a double-blinded study. There have been studies looking at some dietary changes and physical activity that have not shown really clear benefits, though some women do benefit from lifestyle modifications. And these lifestyle modifications are so important for other reasons that we still recommend them.
Starting point is 00:20:24 And Joanne, what would those lifestyle recommendations be? Because I know that listeners will want to know what potentially they can implement that may help with their symptoms. Yes. So it's very important for general health, and some women benefit in terms of hot flashes, night sweats. To have regular physical activity, we describe this as at least 30 minutes of moderate or vigorous exercise, which can include brisk walking, at least five days per week. That's a general recommendation for good health. We also recommend a diet that is largely plant-based, that is high in fruits, vegetables, whole grains, fish, low in red meat, low in saturated fat, fried foods, a diet such as that.
Starting point is 00:21:15 Limiting alcohol, because many women do find that alcohol is a trigger, though it doesn't have to be completely restricted and excluded from the diet, but it can be an issue for many women. Of course, not smoking. Maintaining a healthy weight, which these lifestyle behaviors will help with, being regularly physically active and having a heart-healthy diet of this nature will help with weight maintenance. So those are some of the lifestyle behaviors, not vaping either, neither smoking nor vaping. The extent to which they improve these symptoms is really variable from patient to patient. We can't guarantee that any given woman is going to be responding to these lifestyle behaviors, but they're certainly worth a try because some women do find them helpful and they're so important for generally good health
Starting point is 00:22:11 and health span, longer life expectancy free of chronic diseases. And Joanne, there's a lot of talk about specific supplements, specific nutrients, and also specific foods being able to alleviate some of these symptoms. And my understanding of the evidence is there actually isn't any clear-cut answer for any of these. But given this, again, is something that you've done a lot of work on, I wonder if you could give us a summary of where you think there are foods or nutrients that may benefit symptoms that are quite specific beyond these general healthy lifestyle and dietary recommendations. So some women do notice improvement in symptoms with soy products. There are certain genetic
Starting point is 00:22:59 factors that influence whether women will benefit from soy. But it is certainly worth giving it a try. We're talking about foods such as soy milk, tofu, the soy products that are foods not taking a high-dose soy supplement where there is some concern about a downside. But increasing soy in the diet is definitely worth giving a try. I mentioned that the marine omega-3s or the fish oil supplements did not, EPA, DHA, did not show benefits in a randomized trial, really have not been any dietary supplements that have clearly shown benefit in reducing the hot flashes and night sweats. So unfortunately, there's no magic pill. And avoiding triggers. The triggers are, I know there's a lot of controversy
Starting point is 00:23:53 about really how much benefit you can get from identifying and avoiding triggers. But I found my patients over the years that it has really made a difference for them when they've identified that they do tend to get these symptoms when they drink alcohol or when they have spicy food, warm beverages, and they're able to really reduce the frequency of these symptoms by identifying and avoiding the triggers. And Joanne, we had you on previously talking about supplements. And I loved one of the quotes that I'm now using often that actually, while we don't have clear evidence for all of the supplements, you see them as a good life insurance. And there are a lot of specialist menopause supplements out there to support symptoms
Starting point is 00:24:46 or to support some of the unfavorable health effects that we've talked about, such as bone density loss and increased risk of heart disease. I would love to know your thoughts on whether you think it's worth the extra money, because often these are double or triple the cost of a standard multivitamin and mineral. Is it worth spending the extra money on one of these menopause specialist supplements, or is a standard one as good a life insurance as the menopause one? I think the evidence is building over time that there are many health advantages, health benefits from taking a standard multivitamin. I don't think it needs to be any particular brand product that I would not be promoting here, but it still should never replace healthy lifestyle behaviors. It is not a substitute. It's just a complement to that
Starting point is 00:25:38 as a form of insurance. Before we dive into the benefits and the risks, and maybe actually we could talk a little bit about the controversies. Could you just start by explaining just very simply how HRT works? Because you've talked about how, you know, the menopause is this point where, you know, you stop menstruating, but how does HRT fit into this story? Why does it fit in? So it's believed that the reason women begin to have hot flashes and night sweats and these symptoms, these hallmark symptoms of menopause, as well as some of the genital symptoms that we talked about, is because of the declining estrogen level. And so estrogen is so important. It's important to the brain in terms of there's a thermostat in the brain that helps us adjust to small variations in temperature.
Starting point is 00:26:32 And when we lose estrogen, we become very sensitive to even small changes in body temperature. And this can precipitate a feeling of warmth, a feeling of flushing, and also the sweating starts to occur because we're trying to dissipate the heat that we're feeling. So replacing estrogen then helps directly with the problem, the thermostat in the brain, also the direct effect of estrogen on tissues, including the genitourinary tissues that are important to avoid the vaginal dryness, the discomfort with intercourse, other sexual activities. So that's directly replacing the hormone. Yes. So Joanne, I'm in my mid-40s and lots of my friends are talking about all the different
Starting point is 00:27:25 types of hormone therapy that are out there. Now, traditionally, we've thought of HRT just as being oestrogen. And I know there's some different types of oestrogen, which I'd love to pick up on. But before we do, I'd be really interested to hear why HRT isn't just oestrogen and why there's a lot of talk now about progesterone and also about testosterone even, and what you would recommend for who and why we should use a combination and when we should use a combination. So hormone therapy, what we refer to as HRT, we now call it HT more commonly, but is either estrogen alone that can be used by women
Starting point is 00:28:07 who have had a hysterectomy or estrogen plus progestin because the progestin is added to protect the uterus and women who have not had hysterectomy to protect them against uterine or endometrial cancer. So those are the two main types of hormone therapy. We also have both oral, the pill form of estrogen and patch form of hormone therapy. So I think that that's an important distinction because we know that if estrogen is taken as a pill, it goes directly to the liver and can increase clotting factors. And it may be more likely to lead to an increased risk of blood clots in the legs and lungs than if it's given as a patch. So it's generally believed, even though there are no large-scale, long-term randomized trials of the patch estrogen,
Starting point is 00:29:08 that giving it through the skin, giving it as a patch or a spray or gel on the skin is going to be safer in terms of blood clots than giving it as a pill that would be carried directly through the blood supply to the liver and increasing clotting factors. Another really important distinction, besides whether it's estrogen alone for the women with hysterectomy or a combination of estrogen plus progestin, is whether the formulation is what used to be a very common type of hormone therapy called conjugated estrogen, given orally, or estradiol, which is the more what's called bioidentical form. There are many FDA or government-approved forms of the bioidentical estradiol, as well as a bioidentical progesterone, micronized progesterone,
Starting point is 00:30:08 we are generally recommending that women consider these formulations rather than the older ones that were taken as a pill because of that increased risk of blood clots. It was definitely shown in the Women's Health Initiative that the oral estrogen, estrogen is a pill, and this was conjugated estrogen, and the type of progestin used was associated with a higher risk of blood clots, as well as some increased risk of breast cancer when given in combination, but not when the conjugated estrogens were given alone. I just want to check that I've got that because I think this is really important. I know a lot of people ask lots of questions about this. And when you said more bioidentical, I just want to
Starting point is 00:30:53 make sure that we're understanding that. Are you saying that estradiol is sort of the same effectively as the chemical that our body creates ourselves, whereas the older way that you were given estrogen was somehow different. And this is one of the important changes. Exactly. So the estradiol and the progesterone, the micronized progesterone are considered bioidentical because their chemical structure is virtually identical to what the body naturally produces, what women are naturally producing in terms of estrogen and progesterone. But it's important to understand that there are both bio-identical FDA or government-approved, government-tested forms of these hormones,
Starting point is 00:31:42 and also what's called compounded hormones that you get through pharmacies where there is not the FDA approval for those particular products. The show you're listening to right now that's providing you the latest evidence-based health and nutrition information from the world's top scientists? Well, making it takes a lot of time. We think it's well worth it, all in the name of improving your health. All we ask in return is this, send a link to this podcast to someone you think would benefit. And if you haven't already, click follow this podcast wherever you're listening right now. Okay, let's get back to the show.
Starting point is 00:32:31 And Joanne, there's been a lot of attention on social media around testosterone as well. I wonder if you could give us a summary of what you think its use is, its advantages and risks. The use of testosterone has been somewhat controversial because the randomized trials in women have not yet shown really clear, powerful improvements in terms of sexual function, libido, and results in terms of sexual function outcomes. However, many women do feel that it is making a difference for them and they are interested in taking testosterone. That is usually then given as either a very low dose of the testosterone that the FDA approved products that men take or as a custom compounded product through the pharmacy. This has been incredibly helpful. I would love now to switch to the controversy side of this because I think almost everybody who's going through menopause, unless it was very, very early onset, was aware of this huge press stories, I guess about 20 or so years ago that HRT was deadly and there was this massive reduction. I do remember this, right? Of people suddenly
Starting point is 00:33:52 stopping and it was on the front page of every newspaper around the world really. And then there's been this sort of like reintroduction about the idea of it more recently. Would you be able to give us just a very simple, high level explanation of what happened, what was said then? And then I know that you're actually the lead author on one of the big recent papers, I think it was back in 2017 in Journal of the American Medical Association, really saying, actually, this is the advice that we see today. Could you just sort of paint that picture? Because I think for a lot of our listeners, they're nervous about this, maybe nervous even about what their doctor is saying because of things that they've heard from,
Starting point is 00:34:33 reported about scientific papers in the past. There was enormous misunderstanding about the purpose of the Women's Health Initiative randomized trial. This was the first really large randomized trial of hormone therapy. Two different trials, estrogen alone in women with hysterectomy and estrogen plus progestin in women who had a uterus. And what it was looking at was the benefits and risks of hormone therapy for the purpose of prevention of chronic disease when used by women across a broad range of postmenopausal age groups, 50 to 79. And in 2002, the estrogen plus progestin trial was stopped 3.3 years early. It was supposed to go on for over eight years. It was stopped shortly after five years because it became clear that the risks outweighed the benefits. But let me clarify, these were women on average age 63. Many of these risks were driven by women in their 70s who were the most likely to have many of these cardiovascular events. And it was not a good idea to initiate hormone therapy more than a decade after the menopause started. But overall, the risks seem to outweigh the
Starting point is 00:36:06 benefits when used for prevention of chronic diseases in women who were on average well over a decade past menopause. Now, these results were then extrapolated to women in their 40s and 50s who were on hormone therapy because of hot flashes, night sweats, and were in generally good health to give them the impression that they should, you know, toss out their hormone pills and patches and should never use this medication. And Joanne, when I listened to that, I think that would be my reaction. You're saying, you know, there's some trial, here are some people who are having worse heart attacks. I mean, I understand why as a lay person, why that might be your response? It is understandable, although the Women's Health Initiative investigators never actually told women who were taking hormone therapy in their 40s and 50s for management of hot flashes, night sweats, to toss their hormone therapy pills. And so, Joanne, can you explain?
Starting point is 00:37:30 So that was 20 years ago, the reason why you stopped. I think for lots of listeners now, they're probably thinking about this. They're in perimenopause or maybe recently into menopause. Maybe start with that group at any rate. What are the health risks today? Because there'll be people listening to this still saying, well, you know, I'm having really bad symptoms. So I can see that's going to really help my quality of life. So that's worth a lot. And on the other hand, I'm scared that I might get cancer or something else.
Starting point is 00:37:56 What does the latest science say? What would you, you're one of the world's experts, what would your advice be in terms of the health risks and how you would therefore judge and how you might help to advise a friend of yours thinking about this? My summary of what we know now is that for a woman who is in early menopause, a woman in her 40s or 50s who is having bothersome hot flashes, night sweats, or other menopausal symptoms, the benefits of hormone therapy are likely to
Starting point is 00:38:26 outweigh the risk for that woman. Of course, we need to look at how healthy she is, what her risk factors are. It needs to be an individualized decision. But in general, the benefits will outweigh the risk. And also, the patch estrogen transdermal formulations and the micronized progesterone are likely to have a better benefit risk profile than the pill form of conjugated estrogen together with the MPA progestin that was tested in the WHI. So I think using lower doses, using patch and the transdermal estradiol with micronized progesterone is likely to be safer. And women should not suffer with these symptoms. If they're in early menopause, and that's when the moderate to severe symptoms are more common, and they're in generally good health, they're having these symptoms,
Starting point is 00:39:26 they should see a healthcare provider and try to get help through either hormonal or non-hormonal treatments. And Joanne, can I then ask, I guess, the follow-on question, which is there'll be a lot of people listening to this who are probably getting older, who have been on HRT because they've fitted into the category you're talking about. And then they're trying to figure out, and we've had a lot of questions around this, it's like, well, should I keep on this? Do I need to stop? Because maybe I'm feeling really good and I'm scared about stopping, but I'm also scared about my health risk. What is the day to say, I guess, today?
Starting point is 00:40:07 And therefore, what would your advice be? Well, when to stop hormone therapy is a very important question and also somewhat controversial. However, over time, the thinking has been in the direction of this decision needs to be individualized. It really needs to depend on the overall risk profile of the woman, whether she's a good candidate for continuing, such as a woman who had very severe symptoms and she tries to reduce her dose and the symptoms are coming back. She's at low risk of heart disease, higher risk of osteoporosis,
Starting point is 00:40:48 may have some risk factors for osteoporosis. She could be a very good candidate for continuing longer term. We generally do recommend that women consider stopping estrogen plus progestin when they have an intact uterus and so they're taking the combination treatment that they consider trying to stop within five years because of this increased
Starting point is 00:41:11 risk of breast cancer. They also need to be very careful about getting regular mammograms. However, there will be individual patients who benefit from being treated longer because they're having the severe symptoms, they don't have special risk factors for breast cancer, and they may be more concerned actually about osteoporosis and their bone health. So they may be a candidate for continuing, but they need to understand that the combination therapy, estrogen plus progestin, has been linked to an increased risk of breast cancer after about five years. With estrogen alone in women with hysterectomy, there's more latitude for longer
Starting point is 00:41:52 duration because we do not see this increased risk of breast cancer, especially not within the first eight years or so. And therefore, many women may want to stay on estrogen alone for at least a decade. It needs to be an individual decision. And Joanne, can I ask you one follow-up question on that, just for clarification? So I guess one of the reasons why you might decide you want to keep on doing it forever is you had these severe symptoms. The HRT has had this amazing impact. And I've heard so many people tell me directly about just the extraordinary impact it's had. And I guess you're worried that you'll switch it off and you'll just go straight back to having all of the symptoms that you had. Is that in fact the case? Are you just delaying it and you have exactly the same situation as before?
Starting point is 00:42:41 Or actually, if you are now 10 years on, are you actually likely to not have the same symptoms anymore as you come off? So many, many women will find that the symptoms are much less significant or not even present when they try to come off. Some women will find that it's helpful to taper a little and go to a lower dose for a while and then try to come off completely. But I don't think that women should assume that they're just going to go through the same symptoms, the same severity of symptoms, the same disruption of sleep, but just delayed and deferred until they're 65. No, the expectation and what most women experience is that they are able to stop the hormones. Something that I know lots of people talk about as well related to HRT is how long until it's
Starting point is 00:43:34 going to start working. And this is something I don't think there's very clear answers around. So it doesn't work immediately like the next day. You're going to have total improvement in the hot flashes and night sweats. Overall, it takes about four weeks to really see the benefits. So women should expect that it's going to be a gradual effect. And certainly within four to six weeks, we would expect that they're going to get the benefits. And if not, they may need the dose adjusted, a higher dose, or even a change in formulation. Okay. And now I've got a million dollar question, Jonathan, before you jump in is,
Starting point is 00:44:16 now Jonathan asked at the very beginning of the podcast, when he only allowed you to say yes or no, which I thought was very mean, Jonathan, on this one, is whether HRT helps with weight management during the menopause. And the reason I ask this, because again, as a woman in my 40s, I know lots of women that are saying, oh my gosh, my belly, my body's changing. I'm going to go on HRT to prevent this. What's the answer? More than a yes or no now. It is a complicated answer. There are studies such as the PEPI trial suggesting that estrogen therapy does lead to less gain in weight over the menopause transition than occurs with a placebo. So there does seem to be a difference. But it's not like it eliminates, totally eliminates any weight gain that tends to occur during the perimenopause or the menopause transition. And so
Starting point is 00:45:15 that's why I answered the question, no, that it shouldn't be like considered that even if, you know, lifestyle factors aren't paid attention to and, you know, trying to be physically active and follow a healthy diet, just take hormone therapy, that that's going to take care of the problem of weight gain during this menopause transition, which is quite common. There still is going to be some weight gain and there's also going to be some weight gain, and there's also going to be some change in body composition. So even more important than the change in weight is the change in abdominal fat distribution. There tends to be the deposition of fat in the abdomen and the visceral areas.
Starting point is 00:46:03 The internal organs tend to have more fat surrounding them. I don't think that estrogen completely eliminates that change in body composition that tends to occur during the menopause transition, that women are more likely to have the abdominal fat distribution and some increase in these risk factors, these metabolic risk factors, but it does help to attenuate or lessen the weight gain and the abdominal fat accumulation. Joanne, I have so many more questions and I can feel maybe we will try and see whether we can do like an in-depth topic for people who'd really like to get deeper, but I'm well past time. So Richard, our producer is definitely telling me to stop. I'm going to try and do a summary playback and please keep me honest because
Starting point is 00:46:55 I'm definitely not a doctor or a scientist and pick out what feel like the key things that we've covered today. So the first is we talked about some of the things that you could do that aren't drugs, because you said that's going to benefit anybody who can do that. One of which is regular physical activity. And I think you said 30 minutes of moderate exercise, which means a brisk walking five days a week is going to help. Then we talked quite a bit about diet. Sarah actually showed some really interesting data that had come from one of our big Zoe Health studies showing that actually diet quality, so the difference between a really high quality diet and a poor quality diet, seemed to have a 30% difference in symptoms. So you can see that diet can have some impact. You talked about some specific things you might be able to do. It's interesting, limiting alcohol
Starting point is 00:47:42 was one specific example of something you might be able to do to alleviate symptoms. Also talked about soy. So apparently that is not a myth, but it sounds like it's quite personal. So some people will have a lot of benefit from it. Some it may not have any effect and it needs to be real food like tofu, not a sort of concentrated soy supplement. And in fact, on supplements, you said, don't waste your money on sort of menopause specific supplements, spend the money on real foods, which Zoe is obviously going to love. And then I think we talked about HRT and you said, with the data that you have now and the sciences, you understand it today. I wrote this down because I want to get this right. From a woman in early menopause in their forts or their 50s with bothersome symptoms, the benefits of HRT are likely to outweigh
Starting point is 00:48:29 the risks. So a lot of these studies were on pills and with a different form of estrogen. We've now moved to these patches and I think estradiol, which is therefore supposed to sort of mimic what we have inside us. You touched on testosterone. And my takeaway from that is it is controversial. It's not approved in the US, for example, from the FDA. But you did say if you're having issues, you should discuss with your doctor.
Starting point is 00:48:54 So it sounds like you weren't sort of rejecting it out of hand. And then the last thing you said, I did want to repeat, is there's help available. Do find the right doctor for you. So if you're not finding that you're getting what you need right away, you should feel that, you know, this is important and you should be trying to find someone. It's worth persevering in your words
Starting point is 00:49:14 because actually you can probably find a way to really alleviate these symptoms. Yes, excellent. That's a great summary. Joanne, thank you so much for coming back and talking to us about this very important topic. It was great being here. Thank you for your interest. Thank you, Joanne, for joining me on Zoe's Science and Nutrition today. If you want to understand how best to eat for your health, whether you want to improve
Starting point is 00:49:41 menopause symptoms or not, then you may want to try Zoe's personalized nutrition program. You can get 10% off by going to joinzoe.com slash podcast. As always, I'm your host, Jonathan Wolfe. Zoe Science and Nutrition is produced by Yellow Hewings Martin, Richard Willen, and Alex Jones. See you next time.

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