Menopause & Mitochondria: changes in hormones and how they impact mitochondria
Estrogen doesn't just drive fertility — it's one of the body's key mitochondrial regulators, and losing it changes everything from how you burn fuel to how sharp your brain feels. In this episode, Georgia Truman breaks down the science of ovarian aging and the midlife transition through a mitochondrial lens, looking at what's really happening in the body from perimenopause through to post-menopause and beyond.
She covers:
Why ovarian aging is being called the "canary in the coal mine" for biological aging
The bidirectional relationship between mitochondria and steroid hormone production
How declining estrogen drives changes in glucose control, fat storage, and muscle loss
The mitochondrial story behind menopausal brain fog and the brain's shift to burning myelin for fuel
Why cardiovascular risk rises after menopause, including new research on mitoquinol and vascular function
Practical strategies — from protein and exercise to HRT and phytoestrogens like S-Equol — to support mitochondrial health through the transition
Whether you're navigating perimenopause yourself or want to understand the biology behind the symptoms, this episode reframes menopause as an energetic transition, not just a hormonal one.
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Georgia (00:16)
Hi, welcome back to the MitoPod. My name is Georgia Truman and I am the Scientific Affairs Manager for the MCRP, which is the Mitochondrial Collaborative Research Program. Today we are going to be talking about midlife and mitochondria. Specifically, we're going to have a look at the midlife transition for women. We're going to be talking about ovarian health, perimenopause, menopause, and beyond and how these different life stages go on to affect our mitochondrial health, what role estrogen is playing, and then what you can do to support your body through these different phases. So first we are going to have a look at what is triggering aging specifically in women. So we know that we have chronological aging, which are the years that you have been alive for, and then we have biological aging.
Now in theory, this is supposed to predict how well your body is aging compared to those around you in your age group. So if you're 40 years old, do you have the body of a 40 year old? Or are you aging slowly, like a 35 year old? Or are you aging quickly, like a 45 or a 50 year old? Now, obviously the idea is that you want your body to be younger than you are chronologically.
But what does this really mean and what does it mean for women? So let's have a look at biological aging in women. Let's see what different processes are happening. So for women, biological aging is underpinned by ovarian aging. Now, when I say ovarian aging, I am referring to our reproductive system and how well that is aging or being preserved.
For most women, ovarian aging is going to accelerate in our mid 30s. And yes, this is correlated to fertility, but I really don't want to have a fertility discussion with you guys today. I really want to focus on what the processes are that then go on to influence hormone production that kick starts perimenopause and menopause. So, yes, fertility is important, and I am going to talk a little bit about.
You know, the reproductive process and the metabolic demand that keeping those eggs alive and healthy puts on the body, I'm really focusing on ovaries in an aging context and less about fertility. So with that being said, let's talk about our ovaries and their function. So our ovaries are quite a unique organ because they contain a finite
a non-renewable pool of follicles and these are our immature egg cells. We know that we're born with all of the eggs that we will ever have. And we're actually born with around one to two million egg cells that are consistently lost throughout our life. By our early thirties most women will have around 120,000 eggs left.
And this is because when we menstruate, we are actually releasing around 1,000 immature eggs or follicles, not just one. Yes, one is going to go on to mature into a healthy egg that is viable for fertilization, but we actually lose a lot of those follicles and potential eggs every time we menstruate.
Now it's the maturation of these follicles that cause the production of estradiol, which is our main reproductive hormone. Now the estradiol rises during our follicular phase, and then once we have ovulated and released a mature egg, Estrogen will drop quite significantly. And for some women, this can trigger things like premenstrual syndrome and premenstrual dysphoric disorder. So yes, a change in hormones can go on to cause physical symptoms of pain, but also neurological symptoms and mood symptoms. Maintaining and maturing a healthy pool of eggs or your oocytes is an incredibly energy demanding process and requires healthy mitochondrial function. And at the heart of it, ovarian aging could be considered mitochondrial aging. But we will check back in on that in a minute. Ovaries are of course responsible for reproductive health and fertility, but they are also where the majority of our sex hormones are produced. Like I mentioned, estradiol. Over time
ovarian function is going to decline and this leads to a reduction in the number of eggs that we have as well as the quality of eggs. Like I said, maintaining and maturing these eggs is very energy demanding. Now as our ovarian function declines we also see unstable hormone production. And this is how we transition from healthy, reproductively active in our 30s
into unstable hormones and actually moving into perimenopause in our forties.
Now, part of this is determined by ovarian reserve. So this might be a term that you've heard before. The quality and quantity of your available follicles and eggs is known as your ovarian reserve. And the optimal ovarian reserve is between 18 and 31 years of age for most women. After 31, this is going to start to progressively decline.
And it will start to accelerate after 35. So you've probably heard a lot of discourse online about protecting your fertility, having children before you reach 35, because then that becomes a lot more difficult to conceive. Now, this is true, but it doesn't mean that there is no hope for women over thirty-five. Okay. Now I don't want to get into the fertility discussion in this podcast, but I just wanted to highlight this process because ovarian function and estradiol production or estrogen production is very very important for today's topic, specifically around mitochondrial health. So oocytes are highly dense in mitochondria, and they depend on the mitochondria obviously for ATP production, so that's your cellular energy, but they also need that energy for chromosome segregation and fertilization. So there are a lot of processes that are happening within those egg cells to get them ready for fertilization.
As we age, we see a decrease in mitochondrial function, an increase in oxidative stress, a reduction in energy or ATP production, and an increase in mitochondrial DNA damage. And this all leads to reduced egg quality and function. Our ovaries are typically in a progressive decline from our late reproductive years, which usually starts in our mid-30s. And this gradual decline of ovarian function is going to ultimately culminate in.
menopause. Now this transitional period is characterized by fluctuations and eventually decline of estradiol and progesterone as well as follicle stimulating hormone or FSH. And this all leads to irregular ovulation that then will cease at menopause.
Now, ovarian aging is actually being referred to as a bit of a canary in the coal mine for biological aging because the loss of these hormones, especially estrogen, affects so many systems in the body. So ovarian aging occurs decades before the decline of other systems that lead to recognizable conditions like cardiovascular disease, metabolic syndromes, and even dementia.
So what is menopause exactly? So menopause is typically defined as a clinical milestone. It's really easy to diagnose once you've gone through it, but sometimes it can be difficult for you to track where you are on this menopause journey.
Now it's diagnosed retrospectively. So after twelve consecutive months without a menstrual period, you would then be classified as postmenopausal. You have gone through menopause. Now this is the definition that is used in all major clinical guidance.
But it's not particularly helpful for women who are in their 40s through 50s who are going through this menopause transition. For example, you might have gone nine months without having a period, and then you start to bleed again. Then the clock has to start again, right? But you're still dealing with all of these symptoms. So you might be dealing with a brain fog, you might be dealing with vasomotor symptoms, things like night sweats. So this menopausal transition period can actually last for up to a decade for some individuals and can be starting from as early as your 40s. So there is this phase before you hit menopause, and that is called perimenopause. Now I would urge everyone to have a look at the straw plus 10 criteria.
If you have a look on Google, you're probably going to be able to find a really nice image of a table. Now, this is going to take you through changes in hormone levels as well as changes in menstruation, and then also some commonly associated symptoms. It's going to put it in stages from your late reproductive phase until post-menopause. So you'll be able to see where you're sitting based on your symptoms.
Now this is a really good framework because it recognizes that reproductive aging isn't a single event. It is a staged biological process that involves changes in your menstrual cycle, follicle stimulating hormone, things like your ovarian reserve, and then the timing of your final menstrual period, as well as all of those accompanying symptoms.
So, what is actually happening during perimenopause? Now, perimenopause is a time of instability. It's not just a deficiency of estrogen. This is happening because follicle recruitment is becoming less reliable. So converting those immature follicles into mature eggs is more difficult to do. Ovulation becomes inconsistent, estradiol levels can fluctuate.
And then progesterone can decline early because ovulation becomes irregular. And then things like follicle stimulating hormone and luteinizing hormone can increase as the body tries to overcompensate for the fact that we are not ovulating. So we get this sort of panic rush of these hormones being produced as the pituitary tries to stimulate these ovaries that are not as responsive as they were.
This is why a lot of women can experience symptoms years before they've actually reached menopause.
Now perimenopause is tricky because it is a time of huge inconsistency with your hormones. Estradiol might be high in one cycle and then low in another.
So going to a doctor and having your hormones analyzed at one point in time is not really going to be a good indicator of what is happening in your hormone cycle for perimenopause. You can't really diagnose it on a single blood test. If you're over 45 and you have typical symptoms of menopause alongside changes in your menstrual cycle, so maybe longer time between periods, shorter time between periods, or in between bleeding. Most clinical guidance is going to support a diagnosis of perimenopause. Doctors are going to be relying more on your age and cycle changes and symptoms rather than looking at your hormones specifically.
Now, one of the hormones that might be looked at for your ovarian health, and particularly if you are in your late 30s or early 40s and you are still interested in having children, might be the anti-malarian hormone or your AMH. Now, AMH levels reflect the remaining pull of the growing follicles that are in your ovaries. So it is a marker of your ovarian reserve.
So AMH levels are generally gonna decline as you age reproductively. So it might be a good estimation of the time to your final menstrual period. But it's not that reliable at predicting things like symptom severity or your metabolic changes or brain fog as you go through perimenopause and menopause.
Georgia (12:39)
So, estrogen
Georgia (12:40)
is largely produced by the ovaries, but it is a systemic hormone, which means that it enters the bloodstream and travels throughout the body.
Its job is to help regulate our fertility, of course, as well as antioxidant protection, energy metabolism, cardiovascular function, and even brain health. So, yes, estrogen is extremely important for our reproductive health and fertility, but we can also think of estrogen as an energy allocation signal. Reproduction is one of the most energetically expensive processes in biology.
Growing the follicles, ovulating, pregnancy, placental development, lactation all require coordinated energy production, nutrient partitioning, vascular adaptation, And metabolic flexibility. So it makes sense that estrogen would evolve around not merely a reproductive purpose, but as a hormone that helps to coordinate energy availability through the body.
And this is why we have estrogen receptors that are found throughout many tissues outside of the reproductive system, because estrogen is influencing these organs. So this includes things like skeletal muscle, adipose tissue, which is your fat tissue, your liver, your brain, the vascular endothelium, so really important for nitric oxide signaling and vasodilation, immune cells, and even our bones.
So estrogen receptor signaling is involved in glucose metabolism, lipid metabolism, mitochondrial biogenesis, so making more mitochondria, regulating things like oxidative stress, vascular tone, inflammation, and also brain energy metabolism.
Something that's really interesting about the relationship between mitochondria and estrogen is that mitochondria are actually a part of our hormone factory. Steroid hormone synthesis, so this includes things like progesterone, estrogen, and testosterone, actually begins inside of the mitochondria.
So the first step in steroidogenesis or creation of steroids is the transport of cholesterol into the mitochondria. It then gets converted into pregnanolone by CYP11A1.
Pregnenolone is a precursor for progesterone, androgens like testosterone, estrogens, and glucocorticoids, so things like cortisol. So it means that mitochondria don't just sit as downstream targets for hormones or estrogen specifically, but they are actually needed to produce those hormones themselves. So this is called a bidirectional relationship. Mitochondria help to produce the hormones, steroid hormones like estrogen help to regulate mitochondrial function. Ovarian mitochondrial decline can impair steroidogenesis, remembering that estrogen is made in the ovaries. And declining estrogen can further reduce mitochondrial biogenesis, so making new mitochondria, antioxidant defenses, and metabolic flexibility. So it is a bit of a mechanistic loop.
We need mitochondria to produce these steroid hormones, but the disruption of mitochondrial function can lead to a decrease in hormonal production.
Georgia (15:56)
So, what is the role of estrogen and supporting mitochondrial function? So, estrogen helps to promote mitochondrial biogenesis. So, I've mentioned this a couple of times. So, this is the process of creating new mitochondria and maintaining mitochondrial networks. Estrogen acts through our estrogen receptors. So we have estrogen alpha and estrogen beta receptors.
Estrogen can also influence transcriptional regulators such as NRF1 and PGC1 alpha. So these increase the expression of nuclear-encoded mitochondrial genes. Now what that means is our mitochondrial genome is actually really, really small and it really only has enough information for the physical structures of the mitochondria.
But there are a lot of genes that are housed in the nucleus that can go on to influence mitochondrial function. So these genes, like NRF1 and PGC1 alpha, can support things like mitochondrial DNA transcription and replication and to help the respiratory chain or the electron transport chain when generating ATP. So it provides things like antioxidant defences and kickstart processes like mitophagy and mitochondrial biogenesis. In our muscles and our brain, as well as our vascular tissue, so our endothelial cells, mitochondrial biogenesis supports things like endurance, metabolic flexibility, vascular health, and energy availability, especially in the brain. When we lose this estrogen signal, our tissues can lose some of the signals that help to maintain mitochondrial density and function.
So, estrogen can also regulate mitochondrial oxidative phosphorylation. So, this is the process where we are creating ATP. Estrogen can actually influence our respiratory chain activity and the expressions of genes that are involved in energy production. So this is all about helping cells convert nutrients into ATP. When we lose that estrogen,
we can actually have a reduction in the efficiency of the mitochondrial respiratory chain or ATP production. So this can lead to things like fatigue, worse exercise tolerance and reduced exercise recovery, as well as things like metabolic flexibility and stress resilience. Now this is also related to our basal metabolic rate.
And when we lose estrogen, so looking especially in perimenopause and menopause, we actually just burn less calories at a baseline. Now, if we are burning less calories, so if we have a lower BMR, this means that we can store those calories that are not being burnt as fat. And this is where metabolism comes in as something that is often seen to be disrupted during perimenopause and menopause.
But we will talk a little bit more about that a little later on. We also have antioxidant defenses being impacted. So mitochondria obviously create a lot of reactive oxygen species, which lead to oxidative stress. This is a part of normal respiration. It is just a part of the process of converting nutrients and oxygen into ATP.
Now, estrogen helps to support our mitochondria and our antioxidant defenses by increasing or modulating enzymes like superoxide dismutase. You might have seen this as SOD, glutathione, peroxidase, GPX, and catalase, CAT. These are really powerful antioxidant enzymes. Now, antioxidant enzymes are much more efficient than single antioxidant molecules at neutralizing free radicals.
Our innate antioxidant enzymes help to buffer that oxidative stress and to protect mitochondrial proteins, membranes, and DNA from damage. After menopause, this reduction of estrogen signaling can contribute to more oxidative stress and then less effective antioxidant defenses as well. So this is particularly relevant for ovarian tissue and vascular tissue.
These are very sensitive to changes in the reactive oxygen species balance. And these are also the organ systems where oxidative stress can also accelerate age-related dysfunctions in these areas. So, what about mitophagy and mitochondrial quality control? So mitochondrial health is not just about producing more mitochondria. Obviously, mitochondrial biogenesis and having a high density of mitochondria may confer some benefits, especially in skeletal muscle, but cells also need to know when to remove damaged mitochondria so that you have a healthier overall mitochondrial population. The way that they do this is through a process called mitophagy.
and to help to maintain healthy mitochondrial dynamics. Now this is through processes called fission and fusion, which is just the division and joining of mitochondria. So as we age, there is an association with impaired mitochondrial quality control and estrogen signaling actually might influence the cellular stress response pathway, which is relevant to mitochondrial turnover and mitophagy.
Okay, so let's now zoom out a little bit and take a look at what is happening in the body when we lose estrogen. We're first gonna have a look at our metabolism. So let's start with a loss of glucose control. So estrogen is really important for glucose homeostasis. So it supports insulin sensitivity, which is going to influence glucose uptake and also glucose oxidation in metabolically active tissues. So in skeletal muscle and adipose tissue, estrogen signaling is associated with improved insulin action and glucose transport activity. So this is including things like the GLUT4 related pathways, which bring glucose out of the blood and into cells where it can be processed for energy.
When estrogen declines, glucose becomes harder to move from the blood and into the cells, and this can contribute to insulin resistance and reduce metabolic flexibility. So this is going to put you at an increased risk of type 2 diabetes or at least metabolic syndrome, which is a precursor to type 2 diabetes. So if mitochondria are less able to oxidize glucose efficiently, cells can become less capable of using their available fuel, right? They're not going to have enough ATP. So the issue is not simply that glucose is present. It's just that the cells are less effective at using it. And if it is hanging around in the bloodstream, it can go on to damage nearby tissues, especially our endothelial cells.
So not just glucose metabolism, estrogen is also going to influence fat metabolism. So high levels of estrogen promote fatty acid oxidation, so that's being able to use fats for energy within the mitochondria. And it influences regional fat storage. So before you go through menopause, women are more likely to store fats subcutaneously. So this is just fat underneath the skin. Now it's usually stored around the hips and the thighs.
But after we go through a menopause transition, our fat distribution starts to shift towards greater central and visceral adiposity. So this just means putting on fat in the midsection, which is actually more a male-presenting phenotype. So there was a study done in 2008 by Lovejoy that showed that this menopausal transition is actually associated with an increase in visceral fat.
And a decrease in energy expenditure. Now, this is where I was talking about this reduction in your basal metabolic rate. Now it's also been shown that changes in body composition across the menopause transition, including changes in fat mass and lean mass, are very common. So when we look at this at the tissue level, this decline in estrogen is actually changing a little bit about the adipocyte biology. So things like inflammatory tone and lipid handling change as we lose estrogen.
So things like lipase activity might also increase in our visceral fat depots or deposits, which promotes abdominal fat storage as well. And adipose tissue also becomes a site of peripheral estrogen production, particularly estrone. So estrone is a less potent form of estradiol and it has different biological signalling properties.
So it's no surprise that some women who go through the perimenopause and menopause transition start to gain abdominal fat, even if they don't have any major lifestyle changes. Another thing that happens during the perimenopause and menopause transition is a loss of muscle mass. And what this also means is a loss of mitochondrial reserve. From midlife onwards, women are going to start to lose lean mass. This is clinically important because skeletal muscle is one of the body's largest mitochondrial organs, right? The mitochondrial density is very high in skeletal muscle. Muscle is not just for strength and mobility, it is also a metabolic organ. So it's central to things like glucose deposition, fatty acid oxidation, and insulin sensitivity. If we lose muscle, it doesn't just mean that we reduce strength, it means that we lose some of our mitochondrial reserve. And this is also one of the reasons why we have a lower basal metabolic rate.
So one of the common complaints of perimenopause and menopause is brain fog. That feeling that you just can't find your words, can't put two thoughts together, just don't feel cognitively sharp. Now, brain fog is often dismissed as something that's sort of vague or maybe psychological, maybe something that is put down to stress or unhealthy habits, which definitely can have an impact.
But there is something that is happening in the body in midlife that is to do with the way that the brain is allocated energy. So there is a strong mechanistic basis for this brain energy issue and how that relates to mitochondria. So the brain is obviously very highly energy dependent, right? Our brain uses up to 20% of our energy per day. And it relies specifically on glucose metabolism.
Yes, it can use fatty acids, but it much prefers glucose sugars. Now, estrogen is really important for glucose transport, mitochondrial function, also things like synaptic plasticity, so the ability to create new synapses, and neuronal resilience. So there is a body of research out there that has described estrogen as a master regulator of bioenergetic systems in the body.
but also in the brain. Now during our menopause transition, declining estrogen signaling may reduce cerebral glucose metabolism, not just glucose metabolism in the body. So the brain can start to compensate this by increasing the reliance on alternative fuels. This includes things like lipid derived substrates. Now where is the brain getting the lipid from? Well it's actually linked to changes in myelin sheath and myelin metabolism.
Now our myelin sheath insulates our neurons. Our neurons are quite long. They need to be able to send messages to one another very, very quickly. To get a strong message delivered somewhere fast, it needs to be insulated. This is the myelin sheath. The myelin sheath is made up of phospholipids, which are very fatty molecules.
If the brain doesn't get enough glucose or sugar, it starts to look elsewhere and it can get its energy from fat. So what happens is the brain starts to use the myelin sheath as an energy source. But what this does is it takes the insulation away from the neurons, meaning that our neurons are not firing as quickly and as strongly as they were. So this sort of highlights a bit of a neurodegenerative.
vulnerability that women go through during that perimenopause and menopause phase. Now there's still clinical research that needs to be done in this area, but it is very common to have symptoms such as, you know, poor word finding, poor concentration, lapses in your short-term memory, and cognitive fatigue. And this might be reflected in an energy mismatch in the brain, not just stress and aging. Now there have been some studies and scans on glucose metabolism in the brain in perimenopause, showing that actually we have a decrease in glucose metabolism that seems to, for the most part, write itself after you are in this postmenopause phase. So we think that it is a temporary change in the brain bioenergetics.
So what else is happening in the body? Now, cardiovascular aging is also associated with the timing and onset of menopause. And it's also related to mitochondrial health.
Now we often don't think of cardiovascular disease as a risk for women. Now, this is partly because estrogen is cardioprotective. So up until menopause, women typically have better heart health than men. But the danger is cardiovascular risk increasing after menopause because we are losing estrogen. Now remember, estrogen supports vascular function. And when we lose it, our endothelial cells and our cardiovascular system becomes vulnerable. So, what is actually happening? Now, estrogen helps to promote endothelial nitric oxide production.
Nitric oxide is a gas in the body that promotes vasodilation. This helps the blood vessels to relax and remain flexible so that you can control blood flow. Now it also reduces oxidative stress and supports mitochondrial function in endothelial cells. Estrogen modulates inflammation and also influences lipid metabolism. Especially important for the health of blood vessels.
Because we know things like atherosclerosis are caused by aggravated triglyceride levels and oxidized triglycerides in our blood vessels. When we lose estrogen, we have a decrease of nitric oxide bioavailability. Our endothelial function worsens, so this is the ability for our blood vessels to dilate and to pump blood throughout the body.
Oxidative stress increases, arterial stiffness also increases. Now, arterial stiffness is very similar to endothelial function. As we age, we start to develop fibrotic tissue, which causes stiffening of the arteries. This is going to mean that you have poorer endothelial function, poor ability to control blood flow, and puts you at risk of cardiovascular events.
When we lose estrogen, there is also a risk of an increase in blood pressure, partly because blood flow can't be controlled. And as I mentioned, we have this increased atherosclerotic risk. Now, mitochondria are really important here because endothelial cells require mitochondrial signaling for their redox balance, as well as that things like repair responses and maintaining that vascular homeostasis. If mitochondrial reactive oxygen
species increase and that antioxidant buffering decreases, our vascular aging can accelerate. Now, why is that? because our blood vessels come into contact with blood. Now, blood is not just nutrient in life, it also has toxins, it also has sugar, it has things that can damage those endothelial walls, which is the lining of our blood vessels.
A very recent study by Darvish in 2025 showed that the timing of menopause actually influenced vascular aging as well. So the earlier that someone goes through menopause, the worse off they are in terms of their blood vessel health. Now these researchers wanted to see if there were any mitochondrial mechanisms that were associated with this decrease in blood vessel function.
So they gave mitoquinol, which is a mitochondrial targeted antioxidant, at a very high dose. This was 160 milligrams. So not a typical dose, but they really just wanted to see if there was a mechanism there at play.
Once they had given this dose, they then went and looked at their vascular function and they looked at it through a mechanism called flow mediated dilation, what they found was that by removing mitochondrial reactive oxygen species through using mitoquinol,
Blood vessels from women who went through menopause early then matched those women who went through menopause later in life. And for women who went through menopause later in life, their blood vessel function returned to premenopause status. So there is a mechanism alongside mitochondrial function.
and oxidative stress for protecting our vasculature as we go through this perimenopause, menopause transition. So to put it all together, estrogen is going to help your blood vessels stay flexible. And when that estrogen declines, our blood vessels lose some of that protection as well. And the mitochondria that are inside vascular cells will become more vulnerable to oxidative stress. And this helps to explain why our cardiovascular risk rises after menopause.
Now, what can we do about our mitochondria and our hormone health as we age? Now, there are different avenues that you can take. Obviously, eating well and exercising is going to be great for your mitochondrial health. Now, we have done episodes in the past where we have looked at the different types of exercise that you should do for your mitochondria. I will say that it really is a mixture of high intensity exercise alongside some resistance training. So trying to get four to five sessions of exercise a week if possible and really pushing yourself either a longer duration of exercise or upping that intensity. But I will say that the best exercise that you do is the one that you can do consistently.
If you want to support your cardiovascular health, we would definitely recommend doing some aerobic exercise. In terms of nutrition, it's really important that we get enough protein. One of the reasons why we want to have adequate protein.
is so that we can make sure that we are not losing our lean muscle mass. So aiming for about 30 grams of lean protein with every meal is going to help maintain muscle. Fiber also very, very important for maintaining a healthy digestive system. Now we haven't touched on it in this episode necessarily, but there is the estrobolome
Which is the recycling of estrogen in the gut. Now, this is directly related to your healthy gut microbiome and the microbes that can remove the conjugated estrogen and reactivate it. So having a healthy gut microbiome is also essential. Now I want to touch on something a little bit more medical, which is hormone replacement therapy. Now
Hormone replacement therapy, there's a lot of discussion on whether women should be on estrogen. Now I want to make it clear here that this is just for educational purposes only. You need to be speaking to your physician if you are thinking about doing hormone replacement therapy. And by hormone replacement therapy, I mean a bioidentical estradiol or progesterone combination. And the purpose of
Hormone replacement therapy is not to stave off menopause. It is really more to do with managing the symptoms of menopause once our ovarian reserve has declined. Hormone replacement therapy is not going to restore your original follicle pool in your ovaries.
What it does do is replace or supplement some of that hormonal signaling that the ovaries are no longer providing for you.
According to the North American Menopause Society, hormone replacement therapy is going to be the most effective treatment for vasomotor symptoms and genitor urinary symptoms of
Menopause. It can also help to improve sleep if that sleep disturbance is driven by things like night sweats and vasomotor symptoms. So it really depends on the timing that you're looking at starting hormonal replacement therapy, what the formulation is, what the route of administration is. Is this something that you're going to take orally, or would you prefer to be doing patches? And then also looking at your individual risk.
profile, so do you have a history of estrogen positive breast cancer, then you may or may not be applicable for using hormonal replacement therapy.
Generally, for women that are younger than 60 or within 10 years of that menopause onset and if they don't have any contraindications, the benefit to risk ratio is generally in favour of treatment with HRT so that you can kind of combat some of those really bothersome vasomotor symptoms and prevent some of that bone loss.
There are however other avenues that you can take if you don't want to go on to hormonal replacement therapy. Now phytoestrogens may be an alternative. So I wanted to talk about one phytoestrogen in particular, and this is S-Equol. Now this is because S-Equol is little known. It's relatively new in the phytoestrogen conversation, but it is quite a unique molecule. So I'm just gonna run you through some of the key benefits of S-Equol.
So S-Equol is derived from soy. So we know that soy, things like soy milk, tofu, soybeans, contain isoflavones. Now some isoflavones are phytoestrogens. And this includes things like genistein and daidzein
Now there are certain gut bacteria that can actually convert daidzein, which is one of these soy isoflavones, into S-Equol. And this is a metabolite that has greater estrogenic activity than its precursor, daidezein. The problem is that not everyone has the right gut microbiome to produce this S-Equol efficiently. So in Western populations, it's probably only around 20 to 30 percent. And this is mostly because we just haven't had soy in our diet.
at the same extent that some Asian populations have. And these Asian populations, specifically Japanese and Han Chinese, usually can metabolize S-Equol about forty to fifty percent of the time. Now the prevalence of your ability to produce S-Equol or to be an S-Equol producer is going to vary by your diet, your geography and your composition of your gut microbiome.
Now, S-Equol is quite unique because it has preferential affinity for estrogen receptor beta, not estrogen receptor alpha. Now, estrogen receptor beta is expressed in tissues that are relevant to menopausal symptoms and mitochondrial biology. So this includes things like our brain, our vasculature, and our immune cells, as well as our metabolically active tissues. And it's less associated with our reproductive tissues.
And there have been numerous clinical trials to show that ten milligrams of S-Equol can improve some of the vasomotor symptoms and quality of life measures in menopausal women.
Something else that you can pay attention to is your sleep patterns. And I know everyone says you need to get your eight hours a day, but circadian consistency is really important for mitochondrial function, as well as things like NAD metabolism, glucose handling, and your cortisol rhythm, right? So when you wake up in the morning, you're gonna have higher cortisol levels. Now, this is something that is natural.
But if we have an irregular sleep wake timing and inconsistent eating windows, we can have metabolic instability during perimenopause at a time where you're already likely to have changes in your glucose metabolism and fatty acid oxidation. So it's really important to have consistent sleep, get morning light exposure, and have regular meal timing so that you can support your metabolic regulation.
Georgia (41:09)
So I hope that you've enjoyed today's episode. I really wanted to just sign off with a few words sort of framing our midlife and changes in midlife and how this relates to mitochondria. So midlife is often framed as a hormonal transition, but we also know that that is an energetic transition as well. Our ovaries are among the first tissues in the body to show signs of biological aging.
And because these ovarian hormones are deeply intertwined with mitochondrial function, their decline affects far more than just reproduction itself. It's going to influence how we generate energy, regulate our metabolism, maintain vascular health, and also support brain function. One of the most important takeaways from this episode that I want you guys to remember is that menopause is not a sudden event that begins when our periods stop.
But it's a culmination of a process that may begin a decade or more earlier as ovarian function becomes less stable and our systems that regulate energy become less resilient. So we've talked about how estrogen acts not only as a reproductive hormone, of course it's important for fertility, for ovulation, but it's also a mitochondrial regulator. So we know that changes in body composition, insulin sensitivity, cardiovascular health, and cognition can emerge during this transition.
And many of these changes can be understood through the lens of mitochondrial biology and energy allocation. So it's not a story of inevitable decline, even though yes, menopause is going to happen. But if we can understand these mechanisms, we can ask better questions. We want to know more about muscle health, metabolic flexibility, sleep, cardiovascular risk, and HRT, and then alternatives to that, like phytoestrogens or paying attention to your gut microbiome.
And we'll also have more questions and hopefully more answers on the role of mitochondrial health and ovarian aging itself. The emerging science of this is going to be shifting the conversation from simply managing these symptoms, which is very frustrating for a lot of women to hear, to actually understanding that biology and specifically looking at it through a mitochondrial lens. So I just wanted to leave you with the fact that.
Menopause is not simply a loss of reproductive hormones, but it is the loss of one of the body's major mitochondrial signaling symptoms. Estrogen loss is going to impact your mitochondria. So paying attention to your mitochondria might be a great way to support yourself through these transitional life stages.
