Management of menopause symptoms

I think in terms of the other symptoms, such as vasomotor symptoms, cognitive concerns, often referred to as brain fog, it's really trial and error. It's generally choosing a formulation and just seeing how they go and then being prepared to change the formulation later.

[Music] Welcome to the Australian Prescriber Podcast. An independent, no-nonsense podcast for busy health professionals.

Treating the diverse symptoms of perimenopause and menopause can be a challenge for patients and prescribers alike. The most effective treatment is menopausal hormone therapy, or MHT, but there are also many non-hormonal medications that can help women who have contraindications to or don't want to use hormone therapy. I'm Dr Laura Beaton, and I'm your host for this episode of the Australian Prescriber Podcast.

When I was training as a GP, menopause was one of the more difficult but rewarding areas to get my head around. And so today, I'm absolutely delighted to demystify the treatment of menopause with an expert. Dr Karen Magraith is a GP and the immediate-past president of the Australasian Menopause Society. Karen, thank you so much for your article and taking the time today to speak to our listeners about the best-practice management of menopause.

Thanks, Laura.

And to start with, I actually want to take a step back and ask you just why it's so important that we adequately treat the symptoms of menopause, which, apart from premature ovarian insufficiency, is a physiological, not a pathological process.

Yes, menopause is a normal stage of life for most women, but it can have significant consequences for some women in the sense that some women have severe symptoms. Around about 25% of women will have moderate to severe symptoms, which affect their quality of life or function. So these women really need the opportunity to have their symptoms treated if they want to.

And given that menopausal hormone therapy, or MHT, is the most effective treatment for these symptoms, let's go through the four main regimens for MHT in your article. And so, if it's okay, can we just start with the estrogen-only options. For whom is this suitable?

So estrogen-only is for women who've had a total hysterectomy, that is complete removal of the uterus, including the cervix. So for these women, they usually don't need a progestogen. If you have a uterus, then you need to add a progestogen to prevent endometrial hyperplasia and potential malignancy.

And so for these people for whom we do need to add a progestin, can you talk us through when we're using cyclical versus continuous options?

If the woman is perimenopausal, that is it's less than 12 months since her final period, then we need to use the progestogen in a cyclic fashion. It's usually given for 12 to 14 days of a calendar month. Whereas if someone is postmenopausal, more than 12 months since their final period, then we usually give the progestogen every day. So that's referred to as continuous combined hormone therapy.

And I do want to talk quite a bit about tibolone later, but I wanted to ask for now, how do you choose the most suitable preparation type of estrogen and progestin in your MHT regimens?

Well, I think we need to take a step back and look at the woman's personal medical history, and that includes thinking about things like risk practice for venous thromboembolism (VTE) and cardiovascular disease. If she's at low baseline risk of VTE or cardiovascular disease, then she can really choose between oral or transdermal estrogen. Oral estrogen does increase the risk of VTE, but for women who are at low baseline risk, the risk is still low. Some of those women prefer to have a tablet, so they might choose an oral option. For women with risk factors for VTE or cardiovascular disease, transdermal estrogen is recommended, and that can be given as a patch or a gel.

Are there any things you ask about or consider when thinking about the type of progestogen you choose?

The purpose of progestogen, as we said, was to reduce the chances of endometrial hyperplasia and malignancy. And really any progestogen will do that, but it's a matter of thinking about what adverse effects of different progestogens might be. So we know that the synthetic progestogens, the progestins, can sometimes give better cycle control, better control of bleeding than natural micronised progesterone. So we might choose the synthetic progestogens if we are thinking about gaining good control of the cycle, for example, during perimenopause. But if we think about the bigger picture of risk and benefit, there is some observational evidence that micronised progesterone may confer a lower risk of breast cancer. So that's an important consideration.

And as part of your history taking, are there any particular key symptoms that helps you then determine which MHT regimen or preparation might suit them best? Your article has a great summary table of the common symptoms of perimenopause and menopause, and it affects every body system. And I'll admit sometimes I get a bit challenged with, is this something I can attribute to menopause alone or not? Are there some key things that you are asking for that puts you down one direction or another?

Yes. I think for women who are perimenopausal, if they're having heavy periods or irregular bleeding, we need to think about investigating if the bleeding is abnormal. But once we've ruled out abnormalities, I would suggest considering the levonorgestrel 52 mg IUD for these women because that really serves the purpose of usually controlling heavy bleeding or irregular bleeding as well as providing the progestogen component for hormone therapy. And of course it provides contraception if that's needed as well.

So that's a really good option during perimenopause. But I think in terms of the other symptoms, such as vasomotor symptoms, cognitive concerns, often referred to as brain fog, and other symptoms, I think it's really trial and error. Some women seem to feel better on some progestogens rather than others, but other than that, it's generally choosing a formulation and just seeing how they go and then being prepared to change the formulation later. I would say that there is some thinking that tibolone can be effective for women with low libido. The evidence for this is not really strong, but some women do report that tibolone improves libido. When tibolone is metabolised, it's metabolising into components with estrogenic, progestogenic and androgenic actions. So some women seem to find that useful for libido.

And screening sounds like an important thing also that we need to be aware of and if anyone has a history of breast cancer. How do you talk to patients about all the bad press around MHT and breast cancer?

Yeah, there's a lot of confusion around this topic. The way I approach it with patients is I start off by saying to them that for Australian women, the lifetime risk of breast cancer is one in seven. So on average, one in seven women will have breast cancer during their lifetime, and that is their main risk for breast cancer. And the question is, what is any additional risk from taking hormone therapy? And there is some small additional risk associated with hormone therapy, and it seems to be related to the duration of treatment and probably to the choice of progestogen. So the studies seem to show that longer duration is associated with increased risk of breast cancer, and also that the synthetic progestins are associated probably with a higher risk of breast cancer than micronised progesterone, although we don't have any randomised controlled trials to confirm that.

When starting MHT, how often do you trial being off it, considering that longer duration may increase an individual's risk? Do you reduce dose? Do you stop? What do you counsel people about?

Well, I think once someone's started hormone therapy, if they find it useful for their symptoms and we've got the dose right, then I would review them in a year's time. And really, it's a yearly review to discuss what the purposes of the hormone therapy are and whether those purposes or aims are still being achieved, and what they want to do in terms of do they want to try a reduced dose or do they want to try off it, and then an individualised discussion about the risks and benefits going forward. So there's no sort of arbitrary time limit on how long women can use hormone therapy for, but I do ask them to have an annual conversation about it.

Considering the various different precautions and contraindications, can I ask you to go through some of the other medical risk factors or other history that you talk to people about before starting MHT, but also at those reviews?

Well, the contraindications really are hormone-dependent cancers, including breast and endometrial cancer. So we need to obviously make sure that she hasn't developed those, any abnormal or undiagnosed bleeding, and acute cardiovascular events, acute thromboembolism, severe liver disease, and porphyria cutanea tarda. So those are really the contraindications. But we also need to consider, especially when women have been on hormone therapy for a while, the conditions that might change our type of treatment or that might change our discussion with the patient. So those include a history of past myocardial infarction, TIA or stroke, patients who are at high risk of VTE, those with active liver disease. And for these patients, I would really recommend low- to medium-dose transdermal estrogen if they're using hormone therapy.

The other area to consider is migraine. So migraine with aura is a contraindication for the combined oral contraceptive pill, but it's not a contraindication for hormone therapy, but it is recommended to use transdermal estrogen for women with migraine with aura.

For which context is topical vaginal estrogen most suitable?

Topical vaginal estrogen is for genitourinary symptoms, so vaginal dryness, discomfort with sexual activity, and urinary urge and frequency. So if the woman only has genitourinary symptoms, then you can just treat with topical vaginal estrogen. So it really has a place. And in fact, women can use topical vaginal estrogen indefinitely if they find it useful. And if it's used at the usual doses, you don't need to prescribe a progestogen. For patients with breast cancer, in most cases, we can prescribe topical vaginal estrogen. But if the patient's on an aromatase inhibitor, the idea of the aromatase inhibitor is to reduce systemic estrogen levels down to extremely low levels, and I would actually have a conversation with the patient's oncologist if I was wanting to use vaginal estrogen for someone on an AI. But apart from that, we can really use vaginal estrogen for anybody.

That's great to hear. And apart from improving quality of life for many intrusive symptoms, there are some other great benefits of menopause therapy for many people. Can you talk a bit about bones and even we're looking at some evidence emerging now around cardiovascular health?

Hormone therapy has good evidence for fracture risk reduction, and this came out of the Women's Health Initiative trial amongst others. So we know that while women are using it, they do have a reduced risk of osteoporosis and fracture. Tibolone also reduces fracture risk. So we can consider using hormone therapy for women with low bone density or osteoporosis. Perhaps for women under the age of 60, it might be a preferred treatment rather than going straight to the antiresorptive agents. So that's worth considering for our patients.

The other thing, cardiovascular disease. So for women who are under 60 or less than 10 years from menopause, the studies did show reduced risk of coronary heart disease and reduced all-cause mortality. So there seems to be this sort of window of opportunity for younger women using hormone therapy that it may actually reduce events. However, it's not recommended to prescribe hormone therapy solely for the prevention of cardiovascular disease. The exception for this would be for women with premature ovarian insufficiency, the women under 40. We do prescribe it for cardiovascular protection in that group, but generally it's not recommended for primary prevention of cardiovascular disease.

And of course, as GPs, it's always important that we don't forget the nonpharmacological management of menopause, which as you say is unlikely to stop all symptoms, but certainly can make them more manageable, and it's going to have some other great health benefits as well. In your article, you've got a great table outlining the many nonhormonal medication options, but you also discuss how the adverse effects of these sometimes limit their use alongside the fact that they're actually just not that effective at vasomotor symptom control. What's your approach when you're considering non-hormonal options and their use in menopause?

I think for women who don't have contraindications, I would always offer hormone therapy first after an individualised discussion about the risks and benefits. But some women do have contraindications or they just don't want hormone therapy. And for these women, I would go through the options for non-hormonal medications, and they include the SSRI and SNRI antidepressants and some other medications such as clonidine and gabapentin. But of course, the antidepressants, as GPs know, sometimes can have adverse effects, and this can include in some cases sexual dysfunction and sometimes weight gain, which can be really unwelcome in this age group.

Your article also mentions that there might be some exciting new options on the horizon. Could we briefly touch on estetrol and the neurokinin 3 receptor antagonists?

Estetrol is a natural estrogen. It's found in the human fetal liver, and it's been investigated as a potential estrogen for use in hormone therapy. It's already part of an oral contraceptive formula. It has some potential benefits in terms of risk of VTE, although this hasn't been proven yet, but it may prove to be useful in the future. And the other option is the neurokinin 3 receptor antagonist, and this is a drug that's been designed specifically for hot flashes and night sweats, and there's one particular agent called fezolinetant, which has been approved for use in the US, and it's currently undergoing review by the Australian TGA [Therapeutic Goods Administration], so it may be available in Australia in the future.

It's exciting stuff. Unfortunately, that's just about all the time we've got for the episode, but before we do go, I'd love it if you could do a shout-out to the great resources that you recommend in your article.

Yeah, so there's a Practitioner's Toolkit for the Management of [the] Menopause produced by Monash University team, and this is about to be updated, so there'll be an updated version of this published very shortly. There's a Menopause Health Professional Tool from Jean Hailes for Women's Health, and there are also resources on the website of the Australasian Menopause Society, both for patients and for clinicians.

It's always wonderful to have these resources available at the clinic side. I will say I definitely have used the Jean Hailes menopause tool and actually find their patient information really helpful as well.

Karen, thank you so much for your time. It's been great to talk through all the management options for menopause and to talk about how we really can tailor our advice to each patient and make sure that we adequately treat menopause. I'll also be keeping my eye out for some more options that are in the pipeline.

If you're listening to this podcast and want to know more, the full article we discussed today is available for free on the Australian Prescriber website. I'm Laura Beaton, and thank you for joining us on the Australian Prescriber Podcast.

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The views of the hosts and guests on this podcast are their own and may not represent Australian Prescriber or Therapeutic Guidelines. Karen Magraith has received honoraria for presentations from Mylan, Jean Hailes for Women's Health, and the Australasian Menopause Society.