Watch Dr Larkin review factors in VMS that can inform clinical management for women, including oestradiol withdrawal, individual differences, and pathophysiology.
So in women's health, we like to say that pregnancy is a choice, but if women live long enough, menopause, all women will go through menopause, a 100% of women. And this is clearly a natural phase of a woman's reproductive life, and it's associated with declining ovarian function and decreased oestradiol levels. What we know though is, all women experience the menopause transition differently. Some women have very significant symptoms and others really have mild to none. I like to say, it's the rule of thirds, about 30% of women will transition with relatively mild symptoms. Symptoms that they can manage just with changing their thermostat in their house or taking off blankets when they're sleeping at night. About 30% of women have moderate symptoms, which are more bothersome, but again, they often can manage through lifestyle. And then about 30% of women have the very severe symptoms where they're really disabling. Again, what we know is that there's variability in the severity and frequency of symptoms among women, but there's also, variability and there's race and ethnic variability, but there's also, genetic variability among women in terms of duration of these symptoms. So we know that in the average women, they can last up to about seven years, but there's wide range in that. Some women, they don't last very long at all. Other women, they can last lifetime. In fact, we think about 15%, data suggests about 15% of women will have lifetime vasomotor symptoms. And again, there's racial and ethnic differences and differences among individual women, both on frequency, severity, and duration.
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So this is a very exciting time in menopause management. So thanks to a lot of really tremendous basic science research, we really have developed a better understanding of the pathophysiology of vasomotor symptoms, which has led to very exciting drug development and advances in the space. What we've known for a long time is that oestrogen plays a key role in the development of vasomotor symptoms, but oestrogen is not the whole story. All women, as they transition through menopause, will have declining oestradiol levels as ovarian function stops. What we know though, is not all women experience vasomotor symptoms, so we knew it had to be more complicated than that. Thanks to great basic science research, we now understand that there's a complex process in the brain that controls the thermoregulatory centre. So it involves these new group of neurons in the brain that we understand called KNDy neurons that project into the hypothalamus that are regulated between this delicate balance of oestrogen and NKB. We know that it's this balance between this molecule, this NKB and oestrogen, that leads to the stimulation of these neurons into the hypothalamus, and that controls the thermal regulatory centre. In the absence of oestrogen, NKB predominates. That causes these neurons to be hyperstimulated, which leads to narrowing of the thermal regulatory zone and leads to this hot flash that women experience. Thanks to this basic science research and understanding of this mechanism, we've now been able to develop medications. There's one currently FDA approved that specifically targets this pathway to treat vasomotor symptoms. And so this is a very exciting time in menopause management. And this new drug development has led to us having another tool in our toolbox to treat vasomotor symptoms.
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So I like to say that in 2024, menopause is having a moment. So for those of us that have been interested in working in the menopause space for a long time, it's exciting to see that there's really a big awareness now of the significance of menopause and all of the physiologic impact that it has on a woman's life and healthy ageing. As I mentioned previously, menopause happens to all women if they live long enough and it's represented by that decline in oestrogen levels. And what we know is, although that is a natural phase in a woman's life, if she lives long enough, it has tremendous impact on all of her other body systems. So we know that that significant change in hormones has an impact on cardiovascular health, bone health, brain health, sexual health, overall quality of life, mood, sleep. And although again, it's natural, it has significant impact and is something that really, we now have a much better understanding that we need to evaluate and look at in each individual woman because there are specific things that change, and this is such an important time that we need to address those things as we talk to a woman about ways in which she can age well and age in the best possible health.
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VMS management: A psychologist’s perspective
Clinical psychologist Dr Kingsberg gives a psychologist’s perspective on menopause-related VMS and their impact on women.
Menopause at this moment in time is having a moment. It's in the news, it's in social media, and so you kind of have to be living under a rock if the concept of menopause and talking about midlife health hadn't occurred to you. However, at least in the US media, there tends to be a focus on things like vasomotor symptoms or hot flashes. So most women will associate menopause with hot flashes and night sweats. But I don't know that there is an awareness of the multitude of symptoms that can occur with peri-menopause and menopause and that there tends to be sort of a negative perception of menopause and menopause symptoms. So while menopause is having a moment and we think about women thinking about hot flashes and night sweats VMS, the reality is that there is a multitude of symptoms that might be associated with menopause. And I think that that does women a disservice because they may be seeking help for symptoms that are related to menopause, going someplace else and not really having their peri- and post-menopause symptoms addressed. I think that's also the case for healthcare providers as well. Many healthcare providers who are even more expert in menopause than we'd be surprised to think, often do not, or are not aware of the symptoms beyond vasomotor symptoms that are related to menopause. And so there's a disconnect between women seeking help and some women kind of just learn to live with it. They're just assuming it's a natural part of ageing, and so they are not getting help that they might otherwise get, and the impact in their overall life is pretty significant. We know that symptoms can affect professional life, we know the impact on work performance is significant in terms of billions of dollars lost in work performance as women in midlife are really often at the peak of their careers, and either because of mood symptoms, which are very common, or vasomotor symptoms, or sleep problems, which also are very common. Those really can impact relationships, and work life and overall quality of life.
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I think that one of the missing links in menopause management is women being aware of the variety of symptoms that might be occurring with menopause and clinicians being aware and asking. So, while vasomotor symptoms are very common, they are not necessarily the ones that impact quality of life the most. And if you looked at what are the common symptoms associated with menopause, we don't really have an exact number that we can sort of count on, but the range could be anywhere from eight to, I have to say, probably 30 symptoms that could be associated with menopause. But some of the key ones are going to be sleep disturbance and mood changes. And those are primarily during perimenopause for mood. But, we assume that there has been this domino effect with vasomotor symptoms causing sleep disturbance, and sleep disturbance causing mood changes in this sort of domino linear progression. But what we now understand is that they are interrelated, but not necessarily in this domino effect. That sleep disturbance can occur all on its own, and mood disturbance can occur all on its own, they can impact each other. And that the assumption that every woman is going to wake up because of a hot flash, and that creates a sleep disturbance is not accurate. In fact, 30 to 60% of sleep disturbance is without vasomotor symptoms. So, I think it's important that clinicians understand that they shouldn't assume that if a woman is not having hot flashes or night sweats, that they shouldn't assume that she's not having sleep disturbance, they need to be asking about that anyway. We know that waking after sleep onset, WASO is very common, even with no or mild vasomotor symptoms. And mood symptoms are also very common. And when I say mood symptoms, I don't necessarily mean clinical depression, it could be clinical depression. But what we know is that in perimenopause, if you have a past history of clinical depression, particularly related to postpartum depression or premenstrual dysphoric disorder, but just a history of depression, you are at higher risk to develop a depression, a clinical depression in perimenopause or early post menopause. If you don't have that history, while you're not at particular risk for a major depressive episode, you still may experience some mood symptoms, and there's sort of a constellation of them that could be anxiety, not necessarily depression, or it could be depressed mood or irritability that may not sort of meet the criteria of a depressive disorder. But they are very common. And again, women don't know that that may be related to menopause, and clinicians don't pay attention to those symptoms as much as they pay attention to vasomotor symptoms, but they all can interact. With regard to that sleep disturbance, when I talked about WASO, Wake After Sleep Onset, I think it's also important thinking about that domino effect, to pay attention to the kind of sleep disturbance that a woman may be presenting with. So, as a clinician thinking, are these related to hot flashes? Are they sleep disturbance on their own or are they related to depression? Right. If the sleep disturbance is related to depression, the sleep problem is typically going to be problems falling asleep or early morning wakening. If the symptoms are related to menopause and perimenopause, it's probably going to be the waking after sleep onset. So, women will say, "I don't have any problems falling asleep, and I don't necessarily wake up early, but I wake up during the night and not necessarily with a hot flash."
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In general, currently, women are not being asked or treated with regard to peri- and postmenopausal symptoms. For many clinicians who, or grew up with the initial results of the Women's Health Initiative, they've shied away from thinking about hormone therapy. And therefore, women who come in, they're not asking about menopausal symptoms and/or they're not offering hormone therapy as an option, so many women are going untreated. Many women are not comfortable taking hormone therapy and/or they don't want to be taking antidepressants with potential side effects. Or they're thinking, "Why am I taking an antidepressant when really, my symptoms are vasomotor symptoms?" Or, "Why can't I have a treatment that addresses both my sleep problems and my vasomotor symptoms," right? Because they are not necessarily tied together. Or, "My mood symptoms". And there are other symptoms related to menopause that are also very common that often don't get addressed. For example, lack of sexual desire, which can happen in peri- and post-menopause. GSM, genital urinary syndrome of menopause, which local hormone therapies are very effective in treating, but many women are not aware that local means there's no systemic absorption. Or clinicians are not asking about genital urinary symptoms, right? "Are you having hot flashes, night sweats? No? Okay." And then they move on and they're not addressing those GSM symptoms. Joint pain, very common in peri- and post-menopause, often not asked about, but one of the most significant symptoms that create burden, right? So there are many symptoms beyond VMS that just get... are invisible and don't get addressed. So there's many unmet needs from the current therapies, and also basically because clinicians are not aware of the constellation of symptoms, nor are women. So they're not necessarily seeking help. Oftentimes, they don't seek help until they're really suffering. And that's finally what drives them in to seek help. And then there's a misalignment between that communication between the clinician and the patient regarding menopause symptoms. The term menopause itself creates sort of an unmet need because the language around menopause is uncomfortable for clinicians and women themselves. And so they talk around it and therefore, oftentimes, the real problems and symptoms don't get addressed.
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Read: An article series ‘VMS breakthroughs’ on the impact of VMS and available treatments
