Hormone-based medications for early menopause

It’s replacing the hormones which most women will have until they have a natural menopause, which is at the age of around 50 in this country. So it’s important, because you do get barrier [resistance] from them, to try to give them hormone all the time, either through misunderstanding about the effects of it, or the side effects of it. [They] don’t want to be depending on medication, you know, and all those things. You have to go through it. Once they understand, I think it’s a lot easier, because they will be proactive in looking after themselves.

So can you talk a little about the treatments you go through with the women? So, HRT…

If they, yes. If they have symptoms … easier. It’s easier for the doctor to tell them that they need hormones, because they need something, right? And if they can take hormones, if the premature menopause not because of hormone-dependent cancer, or something like that, then it’s easier for you to give the HRT, and you will try to give it, to alleviate the symptoms, but also for prevention, until the menopause… the natural menopause age, until around 50. That’s one of the things.

The other thing of course, very important, is the lifestyle issue. Anything you can improve in reducing the risks of the long-term issues, I think that’s where you have to look into it. So if you’re talking about lifestyle issue, about the cardiovascular, you want to make sure they’re not overweight, you might want to make sure their cholesterol and everything is okay, they’re not a diabetic and everything else. The calcium itself, the vitamin D, the exercise they’re doing, stop smoking. You know, within range, alcohol, those kinds of things are important.

We need to talk about the positivity of the actual Hormone Replacement [Therapy]. There is so much of the positive things… Beside it gets rid of most of your symptoms, of menopausal symptoms; it also has a protective effect, into your bone, into your cardiovascular, into the development of dementia or neurocognitive issue. So that the benefit to it, you can see that benefit for a long-term. In itself, Hormone Replacement [Therapy] has also been found to reduce things like colon cancer, and all those kind of things. … I don’t think anyone likes to take medication every day, but you know, they will agree to take it.

If there are any relationship issues, psychological issues, dryness in the vagina, what do you want to give there? You know, use lubricant when they’re having sex; use moisturiser for the daily use, if need be. Then you look into the testosterone. Testosterone data is not very clear in how it works in the libido, but in particular it’s [low] in the person who have low libido, and also feeling flat, and tired, and their testosterone happen to be low, and you give them… You know, they do help them. So yes, you can try the testosterone itself. But it is, again, it’s a holistic approach to the woman.

Hormone therapy will help symptoms and prevent – we think will prevent future consequences of not having enough oestrogen that [women were] programmed to have until around age 50. So the cases of breast cancer, and some women with endometriosis also can’t have hormone therapy as well. So we therefore need to skate around that issue and look after bones differently, and look after psychological or brain health differently, and look after cardiovascular health differently.

So look at other markers and different treatments. But if a woman has no other contraindication, they’re not a smoker, they haven’t had clots in the leg or lung, they don’t have heart disease already, and they’re otherwise healthy – I would be having them on some form of hormone therapy. So that could be what we now call MHT, which is menopausal hormone therapy, or HRT as it was known before.

Or if it’s appropriate, the pill. So they’re both forms of oestrogen and progesterone, if – progesterone is necessary for the womb if the womb is still in. It doesn’t matter what choice, and it will really depend on the individual. So some younger women will find it more acceptable to be on the pill, and it’s also that fertility comes in here. So if they do want to still push fertility, obviously the pill’s not a great option. But hormone therapy won’t stop any chances of any treatment for fertility purposes.

So there’s no one right answer. But I would always want to have someone – unless there’s a reason that they can’t have hormone therapy, on either the pill, the combined oral contraceptive pill with oestrogen and progesterone, or hormone therapy with oestrogen and progesterone…

So oestrogen helps the symptoms, helps bone health, helps cardiovascular health, and sort of dictates how we feel, generally. So women without oestrogen at menopause feel differently, some do. Twenty per cent have no symptoms, 20 per cent have severe symptoms, everyone else is in the middle. The progesterone is necessary for womb lining protection. So if they still have a womb and oestrogen only is given, the womb lining can grow, and bad cells can develop, which could be a precancerous sign.

So if a woman still has a womb and hasn’t had that removed for endometriosis, or for bleeding, or for other reasons, she needs oestrogen and progesterone, if she’s on any form of hormone therapy or the combined pill.

The Women’s Health Initiative was a randomised trial which was conducted by the NIH in the United States of America to investigate the effects of hormone replacement therapy on post-menopausal women. Now when that trial was planned, they had to go to the US Congress for funding. And the US Congress at the time said to them, “You know enough already about what happens to women as they go through the menopause at a normal age, so we don’t think you should have the money.”

So the investigators said “Well, let’s do a trial on older women to see whether the effects are the same in older women.” So the average age of the women in the trial was about 63 years. In other words, a good 10 years past the normal age of the menopause. But when the data was released in 2002, and for some years subsequently, the investigators from WHI repeatedly said that the results applied to all women, irrespective of their age, their ethnicity, or their health status.

And that’s been subsequently proven to be incorrect, largely the data that arose from that trial in women who were in their 50s has been very positive, and it’s shown that it was good for their cardiovascular health, good for their skeleton, and had minimal effect on any risk of thrombosis or breast cancer, whereas if you looked at the older women in the trial, it was very obvious quite early on that you should not initiate therapy in any woman who was more than 10 years past her last period.

So the trial was misunderstood and misinterpreted in the first place, and it’s probably taken – well certainly 13 to 15 years since then for the misunderstandings to be overcome, and there is now absolutely a general consensus that hormone therapy in appropriate women is a sensible and wise thing to do, and that the risks are far outweighed by the benefits for women in their 50s. Now as I’ve said already, if you’re in your 30s and you run out of oestrogen there is just absolutely no doubt that the benefits of hormone therapy outweigh any risks associated with its use.

There’s the emotional side and then there’s all the information that they’ve got to take in about the medical side of it and “Now this means that you’re more at risk of osteoporosis. It means you’re more at risk of heart disease”, for example, yeah, and the talk about contraception and hormone treatment, and a lot of women are still resistant to the thought of having hormone replacement therapy, I think. So that’s a whole – that’s a long conversation in itself to say, “It’s safe for you to take” and the benefits versus the risks.

Why do you think that is, the reluctance to go on hormone replacement therapy?

I think it’s the whole fallout from the Women’s Health Initiative and the media coverage of that. I know it was a while ago but that’s really stuck in the minds of a lot of women. I remember being a young GP at the time and people were just coming in all the time just wanting to stop it and even though we’ve had evidence since then to say that, you know, in certain age groups it is safe and so on, but there’s still I think a bit of mistrust of the profession and of the pharmaceutical companies that, you know, “Well, we were told it was safe and that was not true. So what is really the case now?”

So whatever comes out now, I think the women are very sceptical of and there’s also a, there’s a sort of post-modern sentiment with a lot of women that, you know, want to avoid anything that’s “artificial” so, you know, want to avoid drugs in general and there’s certainly a movement away from using pharmaceuticals.

When we talk about the Women’s Health Initiative, it sounds as though we were always right, and they were always wrong. Probably we were giving too many hormones to too many people, and a reflection on what’s happened in the last decade or so has taught us that the dose of hormone you give each woman is different and the duration for which you continue that therapy is different as well, and the way you might deliver it is different.

The way you should make those decisions is in consultation with her. You do not say “Here, take this.” You say, “I think this would be a good idea, what do you think about that? Are you worried about any of this, would you rather have it as a patch or a cream or a tablet, do you want to take it so you have periods or not?” – all those things, involve the young woman in the consultation.

So it’s really around a shared decision making process?

Absolutely it’s 100 per cent shared decision making process, it should be and often is shared by a number of different health professionals. But it has to be shared by the woman herself. And if she’s involved, I think really if she’s involved then her long-term health will benefit from that too.

So with those women, like what are the main issues in treating them, like in terms of you alluded to sometimes them not wanting to take HRT for long periods of time? I mean, is it okay for them to take HRT indefinitely?

Oh yeah, definitely, until at least the age of normal menopause. So you would, I feel it would be almost negligent to not let these people, or encourage them to use some form of hormone replacement, because they will get early ageing, basically.

I suppose the other problem we have is because often some of these people also have issues with absorbing medication as well, so their guts aren’t always good, and so sometimes we need to use transdermal [patches], and then sometimes that works well for a while and then there’s problems with vaginal spotting, then there’s non-compliance because they’re getting spotting, and then we go in a circle again. So there’s often a bit of to-ing and fro-ing and dose organising and stuff like that with prescribing the HRT so that they’re happy with the outcome.

The only thing is I think people sometimes confuse their mood from the medication versus their mood from their menopause, and I think they’re much more likely to have trouble with mood from their menopause than usually from the medication. But, then again, the progesterone is usually the bad guy, so with the PROMETRIUM [progesterone], and I don’t have shares in the company… it’s just that it’s only just come on the market and it’s claimed to have less of those sorts of side effects, as in your progesterone definitely can affect your mood. But I think people are very quick to blame medication, especially when it’s all just happened straight now, like they’ve suddenly stopped their periods at age 35 for no good reason altogether, and they’re feeling very unwell, essentially.

So then you’re sort of starting the HRT. So you can’t… it’s very difficult to separate. It’s like people often blame the HRT for weight gain, just people menopausally generally, and it doesn’t cause it. It’s to do with the menopause and the age increase and all that sort of thing. So it’s always hard to… But you’ve got to… I mean, the point is you should see people regularly so that they can actually work through all that stuff with you. That’s important.

It’s very tricky and it’s hard to know all of the preparations, and yes there are – so most of the pill components are the same synthetic oestrogen – ethinyl-oestradiol – but there’s a huge variety in the different types of progesterones, and different women tolerate different doses and different preparations extremely differently. So some will be great on one pill and some will be terrible on that pill. So it’s a minefield of – and women might have an experience coloured by, “Oh, I had that pill” and “I don’t ever want to have the pill.”

But therefore the knowledge is important. While there are lots of different pills, there are new low dose pills now that we didn’t have say 20 years ago, and they’re probably easier tolerated by some women. So there’s a lot of difference. The hormone therapies also – the HRT or MHT side of things – is very challenging. There are lots of different preparations, and cost is an issue too, for both the pill – some pills are on the PBS, some HRT products are on the PBS, others are not.

The PBS is the scheme whereby medicines are cheaper in Australia. So that will be a factor for some women, that cost is – I might suggest, “Oh there’s a really great low dose pill and you’d be great on that,” but there’s a cost factor, and, “Oh I can’t afford that.” And some can’t take tablets every day. So one young lady I’ve got would be great on tablets, but [she] can’t swallow a tablet. So you’ve got to factor in – and there’s been a recent further issue that there’s been a wonderful hormone therapy patch that you just put on twice a week. It has the oestrogen, it has the progesterone.

It’s a really easy option, it doesn’t have to be a tablet, it’s well tolerated, it’s twice a week. It’s covered by the PBS. But that wasn’t available for six months to 12 months. So you know women are struggling here with what they didn’t want, the treatment they don’t really want, the consequences they don’t want, but when there was a good treatment it wasn’t available. So sometimes it’s a matter of trying what the best treatment is for most women, and I just start with a middle dose.

But in these women you do want to try and get them a higher dose treatment if possible, because we think there’s better bone protection and that more closely mimics the oestrogen they were meant to have in their body. But any amount of oestrogen will help bone health and we think will help the other consequences, and should help symptoms – so it’s a matter of tailoring it. So I try somewhere in the middle, and I usually will try a middle dose of whatever the pill or HRT, and then I usually will get them to come back in six weeks to three months, and then I’ll say, “What were the problems?

What do we need to do? Did you tolerate it?” Then we adjust it. But usually I like to do that three months’ later, because then you’ve had a few cycles, to see if there’s bleeding issues, to see whatever.

How long can it – for some women it can take quite a long time to find the right…

Yes. Some women – most women will be all right on the first choice of treatment I’ve given them, because I’ve factored that in with what they’ve said and what they’ve been on before, and often they’ve tried something before they’ve come to me anyway. So most will be fine and it’s just a matter of tweaking it for bleeding problems or whatever tolerability or dose.

But some women will go from one to the other to the other, and some – I’ve had very few women, but some they just haven’t tolerated anything. And then you just have to say right, we’ve done all of that, we just have to look at your bone health or whatever and go around the other way and make sure we manage that with lifestyle measures and other medications that we might need for bones.

Do you get women asking you questions about bioidenticals?

Yes. So a lot of women do. More the older women, not so much the younger women, probably because it’s quite expensive, and I discourage use of bioidenticals, really for the reasons that you don’t know exactly how much is in there. And because, if you’ve got a uterus, you’ve got to have the correct amounts of oestrogen versus progesterone to prevent endometrial cance. There have been a few cases of endometrial cancer associated with its use.

So the idea behind it is a good one in that it’s hormones that are basically chemically the same; at least that’s the way it’s marketed, as your own hormones. But you can get that in pharmaceutical grade products now. So they’re now calling it body identical hormones; so that’s the oestrogen patch or gel with the micronized progesterone tablet. So that’s basically pharmaceutical grade bioidenticals.

All right. And that is more expensive?

That is more expensive. But it wouldn’t be as expensive, I don’t think, as bioidentical hormones because they’re compounded. They’re very expensive.

When you were saying that now you – practitioners are a bit more circumscribed about how much they prescribe hormone therapy – is that because there is still some potential downsides if it’s given too long?

I think they’re still very worried about breast cancer risk, and it’s very hard to counsel a lady about, “This is hormone therapy, it’s called HRT, or now called MHT,” and they have this immediate preconception – because breast cancer is so prevalent in the media. “Oh I’ve heard that HRT gives breast cancer and I don’t want HRT.” So there’s a very detailed explanation looking through the safety, the pros and cons, knowing the products, which is why some women in their setting will prefer the pill, because they don’t perceive there’s the risk. There’s not this link that’s out there in the media at least. So I think that’s difficult in a busy GP consultation, to do that when their appointments are I think 10 minutes.

Most gynaecologists are quite happy for people to go on HRT as long as they’re monitored. So if you look at the research, and as a GP we see a lot of research over the years and we have a lot of things put to us; this is what you must do. Then five year later, that was wrong. So we’re very – very very cautious about it all.

But some women, come hell or high water they want it. Some women HRT suits really well. Some will get breast symptoms and it’s too much. Some have horrible side effects and don’t like it. And it probably can be tailored more with the tibolone-type drugs that are not quite so oestrogenic and slightly more androgenic are a better approach in those groups.

We’ve got a few women who have got streak ovaries or Turner syndrome or other things like that who are on high dose HRT from a young age and they don’t go through menopause symptoms. But it gets to the stage when they get to menopause – at which point are we going to start turning things down?

And it’s an approach similar to what – they can take the similar approach because they’ve already been on virtual HRT all their life, they can take the approach whether they want to continue with it or not, knowing the risk of breast cancer. I think someone who has been on it from a young age they haven’t got a clear indication to stop. So if they have other cardiovascular risk factors then we could then go to the combined approach; talk to a – probably a general physician or a cardiologist regarding risk.

How long should women take HRT?

That’s an interesting question about the length of HRT use, because I’ve seen quite a few disasters when the Women’s Health Initiative studies hit the presses, the general presses in 2000, 2001, and women just threw away their hormone treatments. Now we’ve got that group who really struggle significantly. We’re seeing situations where women go from a contraceptive pill to then a form of either tibolone or oestrogen patch with progesterone and continue that for five or six years and then say “I might try without it,” and at that time I often get another referral like “Can she come off it?” And the only to answer that is to see what she’s like.

Sometimes what we can do is prematurely remove the ‘scaffolding’ of the HRT, and we talk about [how] this is a scaffold while your brain resets the thermostat, and again I think it’s different for each person. Provided we don’t have any breast pathology or any cervix or any other pathology, and we keep very close tabs on that, or other risk factors, hypertension, clotting problems, if their general health is okay I would say we usually experience women like to keep going with it for at least five, maybe eight years and then slowly wean themselves off. And I trust the intuition of a number of our patients because they will often say things like, “Yeah I’ve got my life back on track now, and I’m happy to see whether I can do without it.”

I remember a 75-year old woman who, as she put it, was on a ‘sliver’ of tibolone. She said, “Look I just need it. I’ve tried to stop it, every time I stop it I feel weaker, I don’t have as much energy.” She also described vaginal dryness, and she said, “I just can’t think as clearly.” So back on a quarter of the tibolone and she was fine. So in that discussion with her, we’ve said, “Well, keep going”. So I don’t think there’s a hard and fast rule except where there is some pathology that we have to always be cognisant of.