HRT for menopause: is it safe?

0:00Welcome to Zoe Science & Nutrition, where world leading scientists explain how their research can improve your health.

0:12Menopause 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, 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.

0:58In 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. 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.

1:37So 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. 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. 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?

2:21Yes. 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. And I was going to follow on. Is HRT safe for everyone? No. Can HRT prevent menopause weight gain? No. 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. Well, 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, because we have this question from lots of people.

3:11What'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 cycles.

4:06This 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.

5:04And Joanne, one of the things I'm really struck about is this shift in talking about the menopause. 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, it was actually pretty taboo just in general. And I think you said quite strongly, really, that it needs to 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.

5:41And 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 patches.

6:28No 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 that's something we'd really like to talk more about how the science has sort of played into the shift in this pendulum.

7:14I guess one question before we start to switch towards HR2 is maybe just thinking about the menopause itself. Do we understand why you're describing some women are going through this with no or very few symptoms and other people, 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 bodiness index do tend to have more frequent symptoms.

7:58Women 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 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 poll in the UK.

8:47We 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, you know, we've published research in this area, I was actually shocked just how prevalent some of the symptoms were.

9:32And 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 you know 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.

10:20And 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 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. Yes. 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.

11:22And given 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. You know, 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 think that there is fortunately increasing attention because women are noticing that this is a neglected topic.

12:09This is something that really is affecting their quality of life, a very large percentage of the population affecting their work productivity, affecting their health. 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.

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13:44Think warm, relaxed evenings with the people you love, sharing delicious, nourishing meals that makes you feel good from the inside out. To download your free guide, simply click the link in the show notes or go to zoe.com slash holiday guide. That's zoe.com slash holiday guide. I still find this thing sort of rather extraordinary that like for so long, nobody has really talked about it, 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.

14:26I'm still struck when you say this, that I mean, even the mild symptoms sound really bad. Like this is, you know, this, this isn't, it does feel as though there's almost like a different benchmark for this than there are for many other things. And 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 be expecting to shrug them off. You'd be expecting to go, well, of course, you need to go and make a whole bunch of changes for them. Do we tolerate this more just because this is a inevitable life change?

15:03You should just put up with it. And are we even now being 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 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 risks.

16:06All 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 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 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.

17:19And 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 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.

18:02And 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 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.

18:46So 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 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, you know, the fish oil, this was not found to be effective in a double-blinded study.

19:35There 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. 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.

20:19We 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. 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.

21:17So 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 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 the symptoms.

22:02And 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 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, you know, the soy products that are foods not taking a high-dose soy supplement where there is some concern about a downside.

22:55But increasing soy in the diet is definitely worth giving it 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 about really how much benefit you can get from identifying and avoiding triggers. But I found in 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.

23:58And 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 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.

24:39Is 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 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.

25:19Could you just start by explaining just very simply how HRT works? Because you've talked about how the menopause is this point where 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.

26:06And 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 types of hormone therapy that are out there.

27:01Now, traditionally, we've thought of HRT just as being estrogen. And I know there's some different types of estrogen, which I'd love to pick up on. But before we do, I'd be really interested to hear why HRT isn't just estrogen 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 who have had a hysterectomy or estrogen plus progestin because the progestin is added to protect the uterus in women who have not had hysterectomy to protect them against uterine or endometrial cancer.

27:57So those are the two main types of hormone therapy. We also have both oral, 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, 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.

29:01Another 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. 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.

29:56It was definitely shown in the Women's Health Initiative that the oral estrogen, estrogen as 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 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 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?

30:40And 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, and also what's called compounded hormones that you get through pharmacies where there is not the FDA approval for those particular products. And Joanne, there's been a lot of attention on social media around testosterone as well.

31:34I 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 compounded, custom compounded product through the pharmacy.