Non-hormone based medications for early menopause symptoms after oestrogen-sensitive cancers

With women who can’t have oestrogen are there other forms that they could potentially use?

Well there is, generally HRT is combined oestrogen and progesterone unless you don’t have a uterus, you have had a hysterectomy, in which case you don’t need the progesterone. The useful bit of HRT is the oestrogen. So, if you don’t give oestrogen to our patients then you don’t tend to give anything else.

I think if you are a well-educated oncologist in how to manage menopausal symptoms then you can certainly initiate people on drugs or management and then send them somewhere, rather than they endure a two-month wait to be seen. So, those are the ways in which I think about my menopausal patients.

Venlafaxine, escitalopram, gabapentin, those would be drugs that one would use for hot flushes, but you know people can be very sensitive to drugs and I really feel that while you shouldn’t underplay the symptoms of menopause, drugs should be a later resort. I wouldn’t say a last resort, because they can be very useful.

Gabapentin seems to be prescribed to some women to help with hot flushes.

Yes.

What is that? What type of drug is that?

Gabapentin was developed as a, an anti-epileptic drug and it’s been shown to be a neurotransmitter modulator so it’s used a lot in things like neuropathic pain, it modulates nerve transmission. So the mechanism of hot flushing is a central mechanism of temperature control regulation and anti-epileptic agents use, are used for epilepsy obviously which is a central nervous thing so it can have an effect on that.

The downside to using gabapentin is the side effects and the main side effect is it makes you drowsy so if you’re on a dose that you may need to supress your hot flushes you may be asleep half the day. Yeah so that’s an issue. If people have hot flushes at night it’s, that’s their prime problem then it’s not as bad because you can take it at night.

If you break it up into different symptoms related to the menopause, so the commonest thing I talk about is hot flushes. So, I sort of have a check list, I’ve written information that I give them about how we – you work your way through it.

So I haven’t got one in here but there’s a brochure about managing hot flushes from this group. So, you start with identifying their precipitants and so trying to prevent the frequency, then I start with the herbal remedies because they’re easy over the counter.

But it’s only just above placebo but it’s not prescription and people often find a herbal remedy more acceptable because lots of their friends who haven’t had cancer who are going through menopause will be taking some sort of herbal menopausal remedy. So, I start with that. Then, we move onto prescription medication, so I’d start with something like venlafaxine, 37.5 mg on to 75 mg and then after that probably move on to gabapentin.

So, the other things that I talk about the hot flushes, I will say acupuncture, I’ve had quite a lot of patients who’ve had a good response with acupuncture for their hot flushes and I have a medical acupuncturist, so a GP with an acupuncture qualification and consults. So, I send people to him and he’s had a lot of success. So that’s my, sort of my – my spectrum for hot flushes.

Also reassure people that they get better with time, even in a natural menopause, you know, hot flushes will get better over time. Okay. And often, some of the really simple things, coming back to avoiding precipitants, so, you know, dress in layers, you know, don’t have a hot drink before you go to bed. There are things like chocolate and red wine which are often clear-cut precipitants for certain people.

So, you can look at your diet. There’ll be things that will set – set you off. All right? So, try and be aware and – and do some linkages and self-manage in that regard. So that’s hot flushes [laughing] that’s only the tip of the iceberg of course because, you know, there’s so many other menopausal symptoms to – to talk about.

So, the next thing we’d talk about would be arthralgia, so there’s a lot of my drugs that I give people, the anti-hormone drugs as a standalone side effect have arthralgia which is joint pains as a – as a symptom and not unsurprisingly quite a lot of the patients going into menopause get joint symptoms. It’s quite surprising how many patients come to me who are on HRT at the time of their cancer diagnosis who have been on, put on HRT for their arthralgia.

I think for the arthralgia, exercise is really quite important as well, so you know there are community based exercise classes that you can tap into that are either, you know, run out of the community health centres or run out of the council, you know, with websites where it’ll say, you know, pink – pink Pilates or what have you, so people can identify that it’s for breast cancer sufferers.

So, then the next thing would be cognitive dysfunction, so that’s a really significant issue for quite a lot of my high profile, you know, high functioning women, and when you combine it with, you know, disabling hot flushes in the middle of a presentation and then a brain fuzz, some of them really, really struggle. So, that’s a lot harder because I don’t have good answers for that. I mean there’s brain training and things on your phone and – but sometimes that can be a real sticking point, the endocrine therapy can be a real challenge and some of them just feel that they can’t cope.

Following cancer, though, I think the other interesting group of hormones are the Selective Estrogen Receptor Modulators, the SERMs. Tamoxifen was one of the original SERMs, but there are many other ones now as well. Raloxifene is another Selective Estrogen Receptive Modulator that we’ve been researching in terms of cognition and mental state stability. So, these are potentially another class of oestrogenic compounds that might be useful and safe in the post-cancer treatments. But, again, we need to get to that first base, which is to get across to clinicians that hormones and mental state are incredibly linked. So, if there is a change in the actual circulating levels of particularly oestradiol and progesterone in the CNS in the brain, that is going to have a deleterious effect on the mental state for a woman.

Women who have had a hormone-responsive breast cancer, so breast cancer or cancer of the reproductive tract, we generally don’t use hormone therapy and we try to use other options.

There are rare cases when it is used but that – in those cases you’d be wanting to have a multidisciplinary approach or perhaps refer on to the professor or have a close discussion with the oncologist involved. I haven’t done that myself but I know that it is an option in some extreme cases. Usually you can treat symptoms pretty well with non-hormonal therapies. They’re certainly not as good as oestrogen. They certainly don’t provide the long term benefits such as the improved bone health. But they can improve quality of life.

They’ve got a lot of side effects, as all drugs do. I think one of the issues is weight gain with a lot of – so some of the medications that we use include antidepressants and also a drug called gabapentin, which is an anticonvulsant and weight gain is very common with some of these medications. One of the antidepressants causes high blood pressure in about 10 per cent of women that use it. So they’re certainly not problem-free. Some women are particularly sensitive to side effects so you can very quickly exhaust the list of things that are available.

In terms of vaginal dryness, there is a vaginal moisturiser, and we suggest to the patients. They need to use it for about six to eight weeks before it has any effect. The way I explain it is, “As you get older you need to put hand cream on regularly and that the lining of the vagina is skin, so it’s a bit like putting hand cream on.” When they come to have sex then they can use a lubricant as well.

And we also talk about increasing the time of foreplay just to help, because they are not as ‘in the mood’ as they used to be so that takes a little work both from them and from their partner to get them in the right frame of mind. But obviously, it is important that when they have sex that it’s not painful.

When a woman embarks on endocrine therapy I actually give out free samples of personal lubricant and what I also say to them in that point too is that building intimacy again whether it be intercourse or not part of the secret to allowing that to evolve again is being prepared.

So letting that spontaneity happen as it may have once and as I said being prepared so use these samples and stash them around your house so you’re not having to go, ‘Oh hang on a minute I need to,’ so you’ve got them there at hand and you know if the situation and time is right that it can just happen and that’s the key and yeah then they’re right and also a big part of, with talking about vaginal dryness too is, is stressing that it’s, it doesn’t just pertain to sexual intercourse, it’s just you know every day and the irritation that it might cause and the importance of actually treating it and because it potentially may not go away and that it’s okay, like it’s normal.

If you go or a chemist and ask, or explain I’m on chemo I have vaginal dryness, it’s okay they’re not going to look at you oddly or anything because it’s a very frequent occurrence for women on endocrine therapy or going through menopause in general.

The one symptom I think that is currently still very badly managed is vaginal dryness. And I think we’re still at a point of loggerheads with the oncology people about treating it properly. I think they’re not acknowledging the data that’s actually there about vaginal oestrogen. And there’s a study currently underway. So hopefully, there will be some more data on that soon.

What I think some people don’t, and particularly non-gynaecologists, don’t realise is that if the vagina’s allowed to atrophy to a degree, it’s not able to be fixed by any version of lubricant or moisturiser or anything like that. It’s actually to do with glycogen. You can’t replace glycogen with anything other than oestrogen. And there’s a degree of fibrosis that is not redeemable. And it’s this vaginal atrophic fibrosis thing that they’ll never be able to be sexually active, penetrative sexually active again. And I think that it is not acknowledged by some of our colleagues that that’s what the problem is. It’s not just about lubrication. It’s actually about the vagina having a distensibility about it. And I suppose we know about it a lot because we see it in post-menopausal women who haven’t used any vaginal oestrogen. And I mean, there are definitely women who you can barely examine with one digit at all in order to say, monitor their other pelvic organs for other reasons.

It’s exactly the same in younger women as well who are x number of years out from losing all their oestrogen. So I have some women who elect to use some vaginal oestrogen acknowledging that there is a very, very, very small risk of it affecting their oestrogen dependent cancer. And I think they should be allowed to take the risks and benefits of everything that they do. It’s not just about us saying you can or can’t do something. It should be something that they should be allowed to make their own judgement if they’re given the information.