Transcript of Q&A session

Navigating your way through menopause can be difficult when you have an existing thyroid condition. Our expert speakers Prof Kristien Boelart and Prof Annice Mukherjee discussed managing thyroid disorders and menopause at our ‘Meet the Experts’ webinar in June 2023. This is a transcript of the patient questions answered live by our experts and chaired by Dr Catherine Napier.

Key:

KB – Prof Kristien Boelaert

AM – Prof Annice Mukherjee

CN – Dr Catherine Napier

What benefits does Hormone Replacement Therapy (HRT) give in terms of cardiovascular health and preventing the development of dementia?

In terms of all the national and international guidance on menopause hormone therapy or HRT, the main indication in the context of natural menopause is to use HRT to treat menopause symptoms first and foremost. This is for as long as that woman needs treatment so there is no time limit on HRT. And, of course, managing those symptoms allows women to stay in the workplace, undertake their care roles and do all the things that they need to do, and they can focus on lifestyle approaches.

In terms of disease prevention, such as cardiovascular disease and dementia, there is no consensus that HRT has any significant impact either way on the prevention of dementia. So, there is a number of different studies and meta-analyses that have been looked at. Essentially, what we have found so far is there is a null effect. Some studies actually suggest HRT can increase the risk of dementia; others suggest it reduces it, and some say there is no difference. It is difficult, as the groups that are studied are quite heterogeneous i.e. different groups of women on different treatments.

There is some interesting work being undertaken on neuroimaging to study the brain changes that occur in the short term with hormone therapies. Even if you see some brain changes over a few months, that does not necessarily mean that it is going to prevent disease in the long term. So, there is no international agreement that HRT should be used to prevent dementia.

HRT is also not recommended to prevent osteoporosis in natural menopause because there are risks with HRT in the long-term. If you are going to use HRT to prevent osteoporosis, you then have to commit to using it lifelong. So, we would not be using HRT to prevent osteoporosis in people who have healthy bones and who do not have indications for HRT treatment such as established osteoporosis. There are many safe approaches to keep bones healthy without risks.

We do use HRT in some women who are going through the menopause transition who have confirmed osteoporosis or low trauma fractures to delay the need for other osteoporosis interventions. So, it is not the same for women who have established osteoporosis as for those women who are just worried about developing osteoporosis but do not have it.

In younger women who have POI (a very early menopause under the age of 40), we recommend that HRT is used to protect bones and the cardiovascular system.

It is a little complicated in terms of the cardiovascular system impact of HRT: We do not recommend HRT is started after the age of 60, this relates to something called the ‘timing hypothesis.’ This means if you take HRT before you have any blood vessel diseases, it is protective. If you take HRT once you have established blood vessel diseases, which are more common as you get older, it seems to accelerate disease. So, we use the ‘timing hypothesis’ to guide us.  If you are under 60 you can usually have HRT safely. However, if you have very high cholesterol or other health issues that are accelerating blood vessel diseases, for example, we know that younger women can have issues with high cholesterol, and other risk factors leading to heart disease and blood vessel disease even when they are premenopausal, we just have to be cautious. Because some women may have established blood vessel diseases at a younger age already.  So, it is very nuanced, and I am trying to describe something that is quite complicated in a short period of time, but the point is it is quite different for every woman.

The guidelines are that we recommend HRT to protect women’s blood vessels and bones when they are younger and have a very early menopause but as they get older the risks start to rise. Certainly, over the age of 60, we do not recommend HRT to be started for vascular disease prevention. The predominant reason for taking HRT is to protect from menopause symptoms to improve menopause wellbeing. (AM)

I am 65 and still have hot flushes. Why won’t my GP give me HRT to manage these symptoms?

There has been a lot of caution among GPs using HRT because of the historic research data we have showing that older women seem to come to more harm with HRT; especially the older fashion HRT that we used in the mega trials that were published in the early 2000s; particularly The Women’s Health Initiative study. In fact, The British Menopause Society is writing a new education tool for doctors to try and help them and I have been involved in that in terms of case scenarios.

In a woman who is 65 and has menopausal symptoms, but is otherwise fit and well and does not have any risk factors, then there is no reason why she should not have a trial of HRT but she needs to be told there is slightly more uncertainty about the risks in older women. In a woman who is 65, I would be asking has she had these symptoms ever since she went into natural menopause because if those symptoms are new there may be other causes for vasomotor symptoms*, fatigue, aches and pains? So, we would want the GP to look at whether there are any other causes of symptoms and treat those before considering HRT.

If a GP is going to start HRT in an older woman, they do need to check whether she has any risk factors for heart disease or blood vessel diseases. If she has very high blood pressure, high cholesterol, diabetes, or if her weight is above target limits, these all need to be managed and addressed alongside HRT. So, we would be using HRT to manage symptoms, but we would need to use that in conjunction with protecting that woman against any other potential health risks that could, potentially, be problematic with HRT. (AM)

I have differentiated thyroid cancer. Should my journey through menopause be any different because of my thyroid cancer diagnosis?

I am assuming the thyroid cancer was treated with a total thyroidectomy, with or without radioiodine, and that therefore the patient is likely to be on levothyroxine. Like I said in my talk, with menopause, and especially when HRT is started, the dose of levothyroxine may need to be adjusted. The target range of levothyroxine will very much depend on the aggressiveness of the cancer and the risk score that has been allocated to this. Other than that, if HRT is started then, yes, we may have to adjust the dose of levothyroxine. Is there a particular risk of HRT making the thyroid cancer come back or get worse? We know there are oestrogen receptors in thyroid follicular cells and there is some patchy evidence that oestrogen may drive thyroid cancer a little bit but that evidence is not clear and it is certainly not well documented that women who go on HRT during menopause when they have thyroid cancer are at significantly increased risk. A history of thyroid cancer is certainly not a contraindication to starting HRT. I do hope that I have addressed what this participant was asking. (KB)

Do women who are receiving transdermal oestrogen, or vaginal oestrogen only, need their thyroid function reassessed like those women taking oral HRT?

The evidence for this is not that clear but I think that with local application of oestrogen it is unlikely that there are significant enough amounts absorbed to affect levothyroxine. I think with transdermal preparations, and Annice may want to come in here as she probably knows all the preparations better than I do, there may actually be some absorption issues that may affect it.

I think if a patient were on levothyroxine and was fine and suddenly starts feeling unwell, that is sufficient reason to check thyroid function just to make sure that things are ok. The symptoms may not be related to the thyroid but it is a simple, inexpensive test. And often a simple adjustment (to levothyroxine dose) can make a big difference. So, that would be my pragmatic approach to that. (KB)

Will supplements containing either iodine or soy affect thyroid function?

As ever in life, if you do these things in moderation, it is fine. If you take a small amount of iodine, it is fine. We are probably mildly to moderately iodine deficient in the UK and if you are a vegan, you are almost certainly iodine deficient. Therefore, taking iodine in moderation is fine. If you take excessive amounts of iodine and soy, then it will affect your thyroid function tests. There have certainly been case reports regarding soy. These are people who take huge amounts and I think it is common sense that as long as you take it in moderation you should be ok. Many of these supplements are fine and contain a lot of good things. As Annice has indicated, many of the general wellbeing supplements help us feel better, that is why they are there, but I would not overdo it. (KB)

Is there a specific dose of vitamin D you would recommend women take? Should women consider taking it all year round? Is there a particular preparation you would recommend and can you come to harm taking too much?

I will start with the last question: You can come to harm from taking mega doses. It is quite hard to overdose on vitamin D. You would have to try very hard! The results of a Newcastle-based study in the Royal College Journal showed very nicely that the safe range of vitamin D, in general, is somewhere between 1000 and 4000 international units a day. 1000 international units is the equivalent of 25mcg and we are usually talking about vitamin D3 because that is the one that is usually available orally in the UK.  So, at somewhere between those doses you are very unlikely to have too much vitamin D. The problem is that we are all very different in terms of our exposure to sunlight, and how much we might get from diet although there is very little vitamin D in normal diets if we are not eating foods that are fortified with vitamin D.

Generally, we say 1000 international units is good for bones but in Adcal D3 there is less than that and the Adcal D3 supplements have quite a lot of calcium in them. There is not really a dose for everybody. The government guidance is much lower. It is 5mcg or 200 international units, which is a tiny dose but that is not specifically for protecting bones. So, when we are looking at protecting bones, the dose is generally around 1000 international units a day. That is definitely very safe, and you can get it over the counter. Unless you have established osteoporosis, you are unlikely to be able to get that on a prescription from your doctor. (AM)

When transitioning through menopause, is it harder for women with a thyroid disorder to lose weight if they wish to?

It is really difficult for anyone to lose weight in our modern society. We live in what we call an obesogenic environment today, so most people find it very easy to gain weight, and very difficult to lose any sort of weight. Weight loss requires a significant calorie deficit which is difficult to achieve for all of us. Modern diets tend to contain more processed foods, even when this is inadvertent. These tend to help us gain weight quite easily.

When it comes to thyroid, and Kristien may wish to say something here too, what I would want is to make sure that woman’s thyroid function is optimised. So, if you are on thyroxine replacement and going through the menopause transition, and perhaps you have gone on hormone replacement treatment, perhaps your TSH may have risen and you may not be optimally dosed with levothyroxine. Kristien may want to talk a little bit about optimal TSH in people on treatment. She talked a little bit about normal ranges for healthy populations. But it’s a little it different when you are on thyroid treatment. We would aim generally to have a lower level of TSH as a target for treatment. But once you have got an optimal TSH for you, it should not be harder than anyone else to lose weight but it is hard for everybody to lose weight.

Actually, I saw a lady in my clinic this morning, who just had to have a few little tweaks to her thyroxine medication. She had been struggling since 2015 when she went on to thyroxine but had probably never really had her dose optimised and she is now on HRT too. She came back today and said she now feels better than she ever has in the past eight years following the tweaks to her medication. I’ll hand over to Kristien now to talk about optimising thyroid medication when on HRT. (AM)

The first thing to note is that everybody has their own set point for thyroid function and that is genetically determined. So, Catherine’s will be different from Annice’s, and Annice’s will be different from mine. Often, we do not know what the patient’s thyroid function was before they became ill, which might help us know what is optimal for them. I have illustrated that there’s a physiological shift in TSH ranges as we age. I personally think that many people feel better when their TSH is around 2. Certainly what the NICE guidelines allow, and what I often do and what Annice just described, is to tinker with the levothyroxine dose a little bit.

What I think we would all agree, is that this is all about personalised decision-making for patients. There is no one size fits all rule. That is not how it works. It is about trying to make the patient feel as best as possible and, as long as that serum TSH does not go significantly below the reference range (because that is when you run into trouble; and certainly, your bone health and cardiovascular system will get into significant trouble), then adjusting the thyroxine dose for that particular patient is a good thing. And many patients do, indeed, feel significantly better from targeting what is probably their normal set point. This is very difficult and in the future, we may have some prediction tools that say this patient has this set point, but that is certainly not routinely available yet. (KB)

When you look at the peak incidence of Graves’ disease, and other autoimmune diseases, is there a relationship between female hormones and autoimmune thyroid disease? Is it clear-cut or not?

The peak incidence of Graves’ disease is between 30 and 60. It is a lot more common in women than in men, as most autoimmune diseases are. Now, a lot of those autoimmune diseases occur at different times and are not linked to reproductive hormones. We know that about 80% of Graves’ disease cases are genetically predetermined, which is why 50% of patients with Graves’ disease patients report that they have a family history. 20% are environmental factors and we know that reproductive hormones do play a role in that because we certainly get changes to the way Graves’ disease behaves when there are changes in reproductive hormones. So, Graves’ disease gets better in pregnancy and flares up after delivery. So, that indicates that reproductive hormones play a role. How clear-cut that relationship is, we don’t know. It is not that women who become menopausal suddenly get this shooting incidence of Graves’ disease because it is multifactorial and 80% depends on the genetic makeup of that person. (KB)

I experienced debilitating symptoms after going into surgical menopause. Do you have any particular recommendations for women who experience this type of menopause journey?

As I understand it, the question is not in the context of thyroid disease, but just in general. A sudden, surgical menopause does tend to be associated with quite a severe set of symptoms. Obviously, it depends on why that woman has gone into surgical menopause. We would generally want to give them hormone therapy but it depends on many different factors.

If you have been very ill, and have had to have a hysterectomy, and you have been bleeding and are anaemic, or you have had cancer; all of those things that have led to that hysterectomy can factor into the symptoms that that woman will experience post-operatively. Also, whether she has had a vaginal hysterectomy or whether she has had a total abdominal hysterectomy might have a different impact on surgical recovery.

If a woman is plunged into surgical menopause from a cancer diagnosis, she may not be suitable for hormone therapy. That obviously can be tough if she went from being premenopausal to postmenopausal, and cannot be given any hormones. Hopefully, her cancer team will be able to support her with all the tools that will provide her with alternatives to HRT and strategies to help with symptoms.

In women who have had a hysterectomy for endometriosis, for example, we would generally be giving oestrogen replacement, and may well additionally give progesterone replacement because of the endometriosis for up to a year, possibly longer, after the hysterectomy.

When you have had your ovaries removed, you lose your ovarian source of testosterone so there does seem to be greater benefit of testosterone therapy in women who have had total hysterectomy with their ovaries removed. Again, it is about tailoring the treatment to benefit that woman’s symptoms.

In the early stages, it is about recovering from the surgery and why the surgery was done, whether there are other things, such as anaemia. As there can be other things going on, including thyroid disease, at the same time. We would generally be putting that woman on treatment to help with her symptoms but it can take time. Gynaecologists often put women on a standard HRT regimen and that will need to be tweaked a little, just as your thyroxine dose will often need to be tweaked after starting on that.  So, I think optimising treatment for an individual woman, and all the things that have happened around that surgical menopause diagnosis, is important. There is not a ‘one size fits all’ really. (AM)

I understand that selenium benefits patients with thyroid eye disease. Does it offer benefits to people with a thyroid disorder, particularly around the time of menopause?

The evidence around selenium’s benefits is mainly in patients with thyroid eye disease. The trials that have been done show that in patients who have Graves’ antibodies to the thyroid gland, selenium will actually bring those antibody levels down. The trials have not shown that taking selenium gives an improvement in thyroid function. Again, I think if you feel better on selenium, I do not have a problem with you taking that. I would suggest, however, that there is no need to buy expensive selenium. Brazil nuts are full of selenium, and they are much cheaper! So, I do not think there is any danger in taking selenium, but neither is there clear evidence, other than in patients with thyroid eye disease, that it particularly helps thyroid symptoms. It may bring TPO** antibodies down but there does not appear to be a link between taking selenium and an improvement in patient symptoms. (KB)

*vasomotor symptoms of menopause are hot flushes and night sweats and are the most common symptoms of menopause.

**TPO antibodies – Thyroid Peroxidase Antibodies are raised in Hashimoto’s thyroiditis (or autoimmune thyroiditis) and sometimes raised in Graves’ disease.