HRT for menopause: Find out if it's right for you

Menopause is a time of significant hormonal changes, which can lead to a range of symptoms. These can severely impact the quality of life.

A drug that promises to reduce menopause symptoms is incredibly welcome, but it has been steeped in controversy.

Hormone replacement therapy (HRT) has been widely debated. There's been conflicting evidence of its effectiveness, with some suggesting that HRT is outright dangerous.

In fact, a massive study 20 years ago linked it to an increased risk of breast cancer. As a result, the number of people taking HRT plummeted. So, should it be avoided at all costs?

In today’s episode, Jonathan is joined by the author of that very study, the esteemed Prof. JoAnn Manson, alongside Dr. Sarah Berry, to explore the science behind HRT and empower listeners to make informed decisions about treating menopause symptoms.

JoAnn Manson is a professor of epidemiology at the Harvard School of Public Health and one of the world's top experts on HRT and menopause. She has run enormous studies to uncover the effects of HRT on women’s health.

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[00:00:00] Jonathan Wolf: Menopause is a condition that affects almost every woman. Symptoms can include hot flashes, disturb, 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, JoAnn Manson, no, in fact, quite the opposite.

Are you confused yet? Luckily, JoAnn 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. 

JoAnn and Sarah, thank you for joining me today. 

[00:01:19] JoAnn Manson: Great to be here.

[00:01:22] Sarah Berry: Great to be back, Jonathan.

[00:01:24] Jonathan Wolf: 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 JoAnn, you may remember, the rules are really tough and today we're gonna 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, are you willing to give it a go? 

[00:01:45] JoAnn Manson: Yep.

[00:01:46] Jonathan Wolf: Fantastic. Alright, 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. 

[00:01:58] JoAnn Manson: Yes.

[00:02:00] Jonathan Wolf: Wonderful. I'm glad you said that. Otherwise, the rest of the podcast is gonna be a bit flat, so that's good.

[00:02:05] Sarah Berry: Oh, I love that. There was no hesitation there whatsoever. 

[00:02:09] JoAnn Manson: That one was easy.

[00:02:12] Jonathan Wolf: There we go. We're just like lulling you into false sense of security. No, not really. Next one. Do most women experience symptoms during menopause? 

[00:02:21] JoAnn Manson: Yes.

[00:02:22] Jonathan Wolf: Should most women consider medication like HRT when going through menopause? 

[00:02:28] JoAnn Manson: No.

[00:02:29] Jonathan Wolf: Very interesting. Is HRT safe for most people? 

[00:02:34] JoAnn Manson: Yes. With some qualifications which we’ll get into.

[00:02:39] Jonathan Wolf: Brilliant. I was and I was gonna follow on. Is HRT safe for everyone? 

[00:02:43] JoAnn Manson: No. 

[00:02:45] Jonathan Wolf: Can HRT prevent menopause weight gain? 

[00:02:50] JoAnn Manson: No.

[00:02:12] Jonathan Wolf: I have stopped having, period. This is a question from one of our listeners. I've stopped having periods but never had menopause symptoms. Should I consider taking HRT?

[00:03:00] JoAnn Manson: No.

[00:03:03] Jonathan Wolf: Wonderful. I think it's gonna be quite controversial, which is gonna be lots of fun. And finally, and you can have a whole sentence now, JoAnn, because we had this question from lots of people.

What's the biggest myth that you hear about HRT. So JoAnn, 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?

[00:03:41] JoAnn Manson: 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 and the ovaries are no longer functioning, so you stop having.

Menstrual cycles. This usually begins average ages 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 because about 75% of women will have some symptoms, but only about 20% will have bothersome hot flashes, night sweats, disrupted sleep, impaired quality of life, or symptoms that are really affecting day-to-day activities.

[00:05:22] Jonathan Wolf: And JoAnn, one of the things I'm really struck about is this shift in talking about the menopause. So I think about, you know, 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. You know, certainly as a man it was completely taboo.

But you know, speaking to lots of my friends and my sisters and all this, this was actually pretty taboo just in general. And I think, you know, what I'm really struck about is you're saying 20% of people, these symptoms are really, you know, bothersome, which I feel is like perhaps a low key way of saying this, but that's actually 20% of all women, right?

So that's an enormous number compared to almost any disease that we talk about. Do you have a view about why this was and like, and I think you said quite strongly, really, that it needs to be very different today.

[00:06:07] JoAnn Manson: 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, you know, hormones, their pills and 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.

[00:07:41] Jonathan Wolf: That's really interesting. Sort of, I guess the way you're describing this, and I think that there'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 HR two 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, 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 we understand what's going on there?

[00:08:15] JoAnn Manson: 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. 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.

[00:09:18] Sarah Berry: I think Jonathan, to add to what JoAnn has said is there was a recent poll in the UK we often do these polls called these YouGov polls, JoAnn, and it looked at, several thousand per 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 and 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. 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.

You know, this is really high, and I'm quite fascinated by some of the data, JoAnn, 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.

[00:11:01] JoAnn Manson: 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, 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 in obviously in a warm room.

Warm temperatures will bring this on. And emotional stress is a major trigger for hot flashes and night sweats.

[00:11:41] Sarah Berry: And one of the reasons I wonder why the menopause it's 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 that statistic that one in 10 females are having to leave their job because of menopause, 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.

[00:12:18] JoAnn Manson: 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's 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. I mean, we're, 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, you know, 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.

[00:13:39] Jonathan Wolf: 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 dunno, 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. Like this is, you know, this isn't it. It does feel as though there's almost like a different benchmark for this than there are for many other things. And that, you know, even listening to you describe this, it feels like you're being a bit tough to me.

Like 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 of course, you need to go and make a whole bunch of changes for them. Like do we sort of tolerate this more just because it is a sort of inevitable life change.

It sort of will, you know, you 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?

[00:14:48] JoAnn Manson: 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 risk.

All women with these symptoms should think about the triggers, you know, try to avoid triggers whenever possible. And you know, 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 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.

[00:16:54] Sarah Berry: And JoAnn, 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. 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 of having brain fog or headaches. They had about 60% greater chance of having, depression, 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, Jonathanc cross-sectional data. So this was data that we collected in one point in time. But I know, JoAnn, 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.

[00:18:54] JoAnn Manson: 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. 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.

[00:19:32] Sarah Berry: and JoAnn, what would those lifestyle recommendations be? Cuz I know that listeners will want to know what potentially they can implement that may help with their symptoms.

[00:19:43] JoAnn Manson: Yes, so it's, 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, 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 and health span longer life expectancy, free of chronic diseases.

[00:21:27] Sarah Berry: And JoAnn, 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.

[00:22:01] JoAnn Manson: 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, but increasing soy in the diet is definitely worth giving a try.

I mentioned that the marine omega three s or the fish oil supplements did not. EPADHA 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've 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.

[00:23:33] Sarah Berry: And JoAnn, 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, cuz often these are double or triple the costs 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?

[00:24:22] JoAnn Manson: 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, would not be promoting here, but it still should never replace healthy lifestyle behaviors. It is not a substitute.

It's just a compliment to that as a form of insurance.

[00:24:50] Jonathan Wolf: Before we dive into the benefits and the risk, and maybe actually we could talk a little bit about the controversies. Could you just start by explaining just very simply how HRT works cuz you've talked about how, you know, the menopause is this point where, you know, you stopped menstruating. But how does HRT fit into this story?

Why, why does it, why does it fit in?

[00:25:10] JoAnn Manson: 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, 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 genital urinary tissues that are important to avoid.

The vaginal dryness, the discomfort with intercourse, other sexual activities. So that's directly, you know, replacing the hormone.

[00:26:28] Sarah Berry: Yeah, so, so JoAnn, I'm in my mid forties and lots of my friends are talking about all the different types of hormone therapy that are out there. Now. 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.

[00:27:03] JoAnn Manson: So hormone therapy, what we refer to as HRT, we, 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. 

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, 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.

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. 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 with 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.

[00:29:54] Jonathan Wolf: I just wanna check that I've got that. Cause 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 wanna make sure that we're understanding that. Are you saying that estradiol is sort of the same effectively as the 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.

[00:30:18] JoAnn Manson: 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 bioidentical FDA or government approved, government tested forms of these hormones, and also what's called compounded hormones that you get through pharmacies where there, there is not the FDA approval for those particular products.

[00:31:04] Sarah Berry: And JoAnn, 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.

[00:31:16] JoAnn Manson: 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, you know, for them, and they are interested in taking testosterone that is usually then given as either a very low dose of the testosterone that, that the FDA approved products that men take, or as a compounded, custom, compounded product through the pharmacy.

[00:32:05] Jonathan Wolf: This has been incredibly helpful. I would love now to switch to sort of the controversy sort of side of this, because I think almost everybody who's going through menopause, unless it was very, very early onset, was sort of aware of these 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 stopping him. 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, you know, what was said then and then I know that you are 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, you know, this is the advice that we see today. Could, could you just sort of paint that picture? Cuz 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, you know reported about scientific papers in the past.

[00:33:16] JoAnn Manson: 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, 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 post-menopausal. 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 aged 63. Many of these risks were driven by women in their seventies 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 seemed to outweigh the 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 forties and fifties 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.

[00:35:25] Jonathan Wolf: And JoAnn, when I listen to that, you know, I think that would be my reaction. You're saying, oh, you know, there's some trial. Here are some people who are having like worse heart attacks, all the rest. I mean, it sounds, I understand why as a layperson, you know, why that might be your, your response.

[00:35:42] JoAnn Manson:  It is understandable. Although the Women's Health Initiative investigators never actually told women who were taking hormone therapy in their forties and fifties for management of hot flashes, night sweats to toss their hormone therapy pills.

[00:36:02] Jonathan Wolf: And so JoAnn, can you explain, so that was the, you know, that was 20 years ago. The reason why you stopped, I think for lots of listeners now they're probably thinking about this. You know, they're in perimenopause or maybe recently into menopause. Maybe start with that, that group. At any rate, what are the health risks today?

Cuz there'll be people listening to this still saying, well, you know, I'm having really bad symptoms so I can see that's gonna 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, or something else. What does the latest, you know, 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, you know, a friend of yours thinking about this.

[00:36:45] JoAnn Manson: My summary of what we know now is that for a woman who is in early menopause, a woman in her forties or fifties, who is having bothersome hot flashes, night sweats, or other menopausal symptoms, the benefits of hormone therapy are likely to outweigh the risks 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. They should see a healthcare provider and try to get help through either hormonal or non-hormonal treatments.

[00:38:12] Jonathan Wolf: And JoAnn, can I then ask, I guess the, the, 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, you are talking about, and then they're trying to. Figure out, and I've, 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, I'm scared about stopping, but I'm also scared about my health risk, you know, what does the data say, I guess, today? And therefore, what would your advice be?

[00:38:48] JoAnn Manson: 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, 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 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 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.

[00:40:48] Jonathan Wolf: And JoAnn, 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? Or actually, if you are now 10 years on, are you actually likely to, you know, not have the same symptoms anymore as you, as you come off?

[00:41:27] JoAnn Manson: So 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 you know, 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 gonna 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.

[00:42:06] Sarah Berry: Something that I know lots of people talk about as well related to HRT is how long until it's gonna start working. And this is something I don't think there's very clear answers around.

[00:42:17] JoAnn Manson: So it, 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 you know, certainly within four to six weeks, we would expect that they're, 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.

[00:42:49] Sarah Berry: Okay, and now I've got a million dollar question, Jonathan, before you jump in is 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 join the menopause.

And the reason I asked this, cuz again, it's a woman in my forties, I know lots of women that are saying, oh my gosh, you know my belly, my body's changing. I'm gonna go on HRT to prevent this. What's the answer more than a yes or no? Now,

[00:43:20] JoAnn Manson: It is a complicated answer. There are studies such as the PEPPI 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, it's not like it eliminates, totally eliminates any weight gain that tends to occur during the perimenopause or the menopause transition.

And so that's why I answered the question n know 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 gonna 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 change in body composition. So even more important than the change in weight is the change in abdominal fat distribution that there, there tends to be the deposition of fat in the abdomen and the visceral areas. 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.

[00:45:13] Jonathan Wolf: JoAnn, I have so many more questions and I can feel, maybe we'll 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 Rich, our producer is definitely telling me to stop. I'm gonna try and do a summary playback and please keep me honest cuz I'm definitely not a doctor or a scientist and pick out what, what feel like the key things that we've covered today. 

So the first is we, Talked about menopause and you said about 75% of women have, symptoms and 20% have really bad symptoms they're having a big impact on their life. We then talked about some of the things that you could do that aren't drugs because you said they're sort of gonna benefit anybody who can do that.

One of which is regular physical activity, and I think you said sort of 30 minutes. Of moderate exercise, which means like a brisk walking five days a week is going to help. Then we talk 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 qualities are 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 the diet can have some impact. You talked about some specific things you might be able to do. It's interesting in limiting alcohol. 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, You know, with the data that you have now, and the sciences, you understand it today.

I wrote this down cause I wanna get this right from a woman in early menopause in their forties or their fifties with, you know, bothersome symptoms. The benefits of HRT are likely to outweigh 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, you know, in the US for example, from the FDA, but you did said if you're having issues you should discuss with your doctor. So it sounds like you weren't sort of rejecting it out of hand. And then the last thing you said I did wanna repeat was, There's help available, you know, 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 to find someone. It's worth persevering in your words, because actually you can probably find a way to really alleviate these symptoms.

[00:48:06] JoAnn Manson: Yes. Excellent. That's a great, that's a great summary.

[00:48:10] Jonathan Wolf: JoAnn, thank you so much for coming back and talking to us about this very important topic.

[00:48:15] JoAnn Manson: That was great being here. Thank you for your interest.

[00:48:21] Jonathan Wolf: Thank you, JoAnn, for joining me on ZOE Science & Nutrition today. If you want to understand how best to eat for your health, whether you want to improve menopause symptoms or not, then you may want to try ZOE's personalized nutrition program. You can get 10% off by going to As always, I'm your host, Jonathan Wolf. ZOE Science & Nutrition is produced by Yella Hewings-Martin, Richard Willan, and Alex Jones here at ZOE. See you next time.