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Hey everybody, it's Mikki here. You're listening to Mini Mikkipedia on a Monday and today I want to chat about a new paper that was just published a couple of weeks ago actually about menopause and metabolism and specifically whether menopause really does slow your metabolism. Now this came up on my feed on social media from Dr. Mary Claire Haver. As you know she's a

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big voice in this menopause space. I like a lot of the information she provides. Don't love all of it, particularly some diet related stuff I had questions over. Anyway, she was the first that I'd seen chat about this paper. And so I made it my business to get the paper myself just to have a look over it. Firstly, of course, is the idea that menopause would slow your metabolism is a familiar one with any woman.

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at that life stage. And often this is what we hear. We see it on social media, talk about it with our friends. You know, this idea that going through menopause slows your metabolic rate. And whether or not this is actually true is up for a lot of debate, if you like. Of course, this goes against maybe what Ponser and colleagues found with their very big observational study, looking at thousands of people across the lifespan and showed no real change in metabolic rate.

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from the age of about 18 to 60. However, I would say that the answer at this point is probably it is complicated. And what I'm discussing today is a new narrative review, which pulled together evidence on energy expenditure and fat oxidation across the menopausal transition. And I'll say that the picture is a little bit more nuanced than you'd think from scrolling Instagram, but it's not a solid nail in the coffin for calories in, calories out at all.

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which by the way is how Dr. Mary Claire Haver was selling it. Anyway, today I'm gonna walk you through what this paper found, where it's strong, where it's weak, and what it might mean for you. So firstly, I'll link the paper in the show notes. It's a narrative review published in the journal Climacteric by McCante and colleagues out of a university in France. They looked.

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at the existing research on every compartment of daily energy expenditure across the menopausal transition. That means resting metabolic rate, sleeping metabolic rate, the thermic effect of food, and physical activity energy expenditure. They also looked at substrate oxidation, specifically how well women oxidize fat and the proposed mechanisms involving estrogen. Now, this is an important caveat up front. This is a narrative review. It is not a systematic review. It is not a

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meta-analysis of studies or meta-regression of studies or anything like that. So there is no formal research methodology and there is no assessment of risks of bias. So it's very interpretation heavy. So I just want you to keep that in your back pocket as we discuss some of the findings of the paper and why some people are interpreting it to mean something which might not actually be the case. So first let's start off with resting metabolic rate.

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because this is where most of the research has focused and RMR makes up about 60 to 70 % of your daily total energy expenditure. So it's the biggest slice of the pie. Some studies do show that RMR declines with menopause. There was one cross-sectional study found that in sedentary post-menopausal women, they had about a 10 % lower RMR than sedentary pre-menopausal women. Even when fat-free mass assessed by hydrodensometry

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didn't differ between the groups. But here's the thing, that is one study. Other studies found that when you adjust RMR for fat-free mass, those differences between pre and post-menopausal women disappear. Fat-free mass accounts for roughly 72 % of the variance in RMR in post-menopausal women. And one observational study pulling data from four separate studies found that chronological age, not menopausal status,

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was inversely associated with RMR, whether it was in absolute terms or whether it was adjusted for fat-free mass. And there's also a really clever study where they chemically suppressed ovarian function in premenopausal women using a gonotropin-releasing hormone agonist, or GnRH. And this is a drug that initially stimulates, then effectively shuts down the reproductive hormone system. And they did this for five months.

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Now, RMR did decrease with the suppression and estradiol replacement partially attenuated or partially improved that. So there's a small amount of support for a direct role for estrogen in this pathway. But other longitudinal data has showed no change or even an increase in absolute RMR across the menopausal transition. So, as a lot of science is a little bit like this, what is the bottom line for RMR? So there's a signal.

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but it's not clean and some of it might be menopause, a lot of it is age and a huge amount of it tracks back to fat-free mass, which of course, a large percentage of our fat-free mass is muscle mass. Now, what about fat oxidation? So this is where things can get a little interesting. And this is where I wanna spend a bit more time because I think there are just a couple of things to highlight here. Firstly, there was a four-year longitudinal study that found 24-hour fat oxidation

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decreased by 32 % in women who transitioned from premenopausal to postmenopausal. Women who stayed premenopausal during that follow-up period did not see that decline. And I do think that that is a meaningful finding. Fat oxidation, just FYI, is an important marker of metabolic flexibility in your body's ability to burn fatty acids. It's different from fat loss, but it can be related. In an acute cross-sectional study in perimenopausal versus

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premenopausal women, was no difference in resting substrate oxidation after an overnight fast, meaning there was no difference between the levels of fat being oxidized or carbohydrate being oxidized, regardless of whether you were pre or perimenopause. Interestingly, those perimenopausal women had about a 17 % higher salivary estradiol than the premenopausal women.

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Now that might sound surprising because of course during perimenopause we're supposed to see estradiol drop off as we head into this transition to menopause. But estrogen during perimenopause doesn't just decline steadily and gently. During perimenopause, estradiol levels can spike up to three-fold higher than what you'd see in a normal cycling premenopausal woman, alongside periods where levels crash well below normal. The hypothalamic pituitary ovarian axis

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is losing its fine-tuned feedback. So you can get these exaggerated surges of FSH, or follicle stimulating hormone, trying to recruit follicles which can drive these big estradiol spikes. So if you catch a perimenopausal woman on a high estradiol day, which is what likely happened in that study, her metabolic profile might look indistinguishable from, or even better than, a regularly cycling woman.

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And that is a real mythological headache for researchers, particularly if it's like a one point in time measure. It is one of the reasons cross sectional snapshots in this population are so unreliable and why the evidence based on perimenopause specifically hand look quite messy. Now, another finding in this review, which I think deserves attention is sleep. The narrative review pointed to a study by Grant and colleagues and Grant and colleagues took

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premenopausal woman aged 21 to 45 and looked at two things independently, sleep fragmentation, assessed properly by Holley's semnography, and estrogen suppression via a GNRH agonist. And then they looked at the combined effect. What they found was that both sleep fragmentation and estrogen suppression independently reduced fat, fasting fat oxidation.

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but without a synergistic effect. So they didn't amplify each other, but each one on its own was enough to shift substrate oxidation away from fat and critically neither affected total energy expenditure, which is what we're the overall sort of umbrella aim of this narrative review is trying to establish. But it was specifically fat oxidation that took the hit. Now the review sites prevalence data showing that sleep did.

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disturbances affect somewhere between 40 and 69 % of women across the menopause transition, and importantly, those disturbances appear to be independent of age. So you've got two things happening simultaneously. Estrogen is declining and sleep is fragmenting, both are independently suppressing fat oxidation. But interestingly, while the authors mentioned this, that the sleep fragmentation is an interesting pathway,

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They didn't actually ask what was driving it. The paper frames sleep disturbance in the context of low estradiol and higher FSH, and that's what correlates with more nightly awakenings in the data they cite. But that is an association and it's not a mechanism. And if you think about it mechanistically, the primary sleep promoting ovarian hormone, it's not estrogen, it's progesterone. I'm not saying estrogen doesn't play a role in sleep, but if you talk to any clinician,

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they're going to flag progesterone as one of the main hormones to consider. Now progesterone acts on the GABA-A receptors through its metabolite allopregnanolone. And this is essentially a neurosteroid with sedative, anxiolytic, and sleep promoting effects. It's the same receptor system that benzodiazepines act on. Interesting. So when progesterone drops, which it does early and erratically in perimenopause because you're having more

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and ovulatory cycles, you lose that GABAergic sleep support. That's your consolidated sleep architecture falling apart. More awakenings, less deep sleep, more time in lighter sleep stages. I hear this all the time from my perimenopausal clients. Now estrogen, as I said, it does play a role in sleep too. It influences thermoregulation and serotonin pathways. And hot flushes driven by estrogen withdrawal can certainly wake a woman up.

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But the loss of that deep consolidated sleep architecture, that's primarily a progesterone story. This is exactly why so many perimenopausal women report dramatically better sleep on progesterone supplementation. That's progesterone and not progestin, by the way. It's not a sedative in the traditional sense, but it is restoring a physiological mechanism that's been disrupted. So, if the grant data tells us that sleep fragmentation independently impairs fat oxidation,

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And if the sleep fragmentation in perimenopause is largely driven by a progesterone decline, then addressing progesterone isn't just a sleep intervention or a cycle regulation tool. It's potentially a metabolic one too, through this independent pathway. Restore that consolidated sleep and you may be recovering fat oxidation capacity that's been lost, regardless of what's happening with estrogen. Now, as I said, this paper didn't make that connection, which...

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know, could be a gap in the paper but you can't cover everything I guess. But they've got the data showing sleep fragmentation in pears fat oxidation, which makes a lot of sense. They've got the prevalence data showing most women have disrupted sleep across the transition, but they don't ask the next obvious question, which is what's driving that fragmentation and what happens metabolically if you fix it. So I thought that was super interesting, but I do want to be clear about this. Reduced

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Fat oxidation on its own doesn't determine fat gain. So energy balance will still win out here. You can have impaired fat oxidation all day long, but if you're in an energy deficit or at maintenance, you're not going to accumulate fat mass. The substrate you oxidize does not override those thermodynamics. What reduced fat oxidation does is change the ease with which someone maintains energy balance.

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If you're burning proportionately less fat and more carbohydrate at rest, during sleep, and during exercise, you're potentially more reliant on dietary carbohydrate to meet immediate fuel needs. And dietary fat is more likely to be directed towards storage rather than oxidation. So over time that can create a metabolic environment with small energy surpluses, ones that might previously have been buffered, are more readily partitioned towards fat. So it does lower the margin for error.

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Also, that drive for carbohydrate changes your appetite response, changes your blood sugar regulation, potentially increases cravings for these processed refined foods that makes it easier to overeat. So I think that's a big part of this picture as well. So the grant finding is important, not just because sleep fragmentation alone is going to make someone gain five kilos, but because it's one more variable tilting the playing field and it's...

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potentially addressable through progesterone as part of the picture through sleep hygiene through treating the fragmentation itself rather than just accepting it as part of the menopausal transition. So staying on sleep then the sleeping metabolic rate itself also appears to decline looking at this narrative review that same four year longitudinal study that I mentioned found that the decrease in sleeping metabolic rate was about one and a half times greater in women who became postmenopausal and

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compared to those who remained premenopausal. That accounts to about 7.9 % versus 5.3%. So there does seem to be an interaction between hormonal decline and age-related changes. That study that gonadotropin-releasing hormone agonist study, which I mentioned earlier, also showed decreased sleeping metabolic rate with ovarian suppression, as I mentioned. And interestingly, as I said, estradiol replacement didn't restore it.

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What does that mean about sleeping metabolic rate? Possibly, as the authors also suggest, this just flags up methodological issues. Getting accurate sleeping metabolic rate data when someone is sleeping in an unfamiliar metabolic chamber, genuinely tricky, right? And we are governed by the data we've got. So do just remember that. What about thermocuffective food? So this is the energy cost of digesting and processing your meals, and it accounts for about 10 to 15 % of

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total daily energy expenditure. Now, the evidence from this review does not support a significant menopause-specific effect on TEF. That Grant et al. study looking at that suppressed ovarian function did not find any change in the thermic effect of food. A clinical study comparing pre and post-menopausal women found a similar TEF. So, during the menopause transition in your late 40s and early 50s,

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the thermic effect of food or the energy cost of digestion probably isn't a major lever. However, interestingly, a study by Du and colleagues has found though that both total thermic effect on food and thermic effect of food expressed as a percentage of meal size was significantly lower in older adults. Both men and women aged around 60 compared to younger adults aged around 18 to 35. And this is held even after adjusting for fat-free mass.

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total fat mass and subcutaneous fat mass. So it isn't just a body composition effect. Now the mechanisms aren't completely nailed down, but sympathetic nervous system activity tends to decline with age. And that is one of the drivers of diet induced thermogenesis. These also reduce splenic blood flow. That is less blood supply to the gut and liver post meal. And this could affect the efficiency of nutrient processing.

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and changes in insulin sensitivity likely play a role too, since insulin-mediated glucose disposal is in itself a thermogenic process. One last thing of course is, you know, we aren't able to digest protein as well in meals, so that the digestion process of protein may also go down as we age. The timing here is the key takeaway. The paper suggested that the TEF decline becomes more significant from

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age 60 onwards. So for the typical woman in her late 40s and early 50s going through perimenopause, probably isn't the compartment to worry about. To be fair, you can't do much about that anyway, other than having an awesome diet. But for older clients, it's worth keeping it in your back pocket because if somebody has already lost lean mass, is less active, has reduced fat oxidation, and now TEF is also declining, those small decrements start stacking. And this really is the theme of the whole review.

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No single one of these changes is dramatic on its own, but collectively they shift the energy balance equation enough that what used to work might not anymore. The good news is that things that support TEF are largely the same things that support everything else. Adequate protein, maintaining lean mass and staying physically active. These are the key pillars to maintaining energy expenditure. And

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Lastly, let's chat about physical activity energy expenditure, which the review also covered. Duvall and colleagues conducted a five-year longitudinal study and showed that time spent in moderate physical activity was highest about three years before menopause, and then it declined. After menopause onset, sedentary time increased. Women who became post-menopausal over that five-year period showed a significant decrease in physical activity energy expenditure.

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Grant and colleagues found that physical activity energy expenditure decreased about 8.4 % with ovarian suppression alone, but not in women who also received estradiol. So that does support a hormonal component, right? But it also raises the question, how much of the decline in physical activity is hormonal and how much is behavioral? Because the answer to that question gives you very different intervention strategies. For exercise specific substrate oxidation,

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One study found that postmenopausal women had about 33 % lower absolute fat oxidation during moderate intensity cycling compared to premenopausal women, which I think we knew. But after adjusting for fat-free mass, that difference did drop. It remained significant at 23%, but it wasn't as high. So there does appear to be this genuine hormone effect on fat utilization during exercise, though fat-free mass is again the major player.

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And what I will also say to this is that diet is a huge component of being a better fat burner in general. And this is often not chatted about in these conversations. I mean, that's an intervention and something for another day, but I thought I would flag it. So what is the mechanism here behind the physical activity energy expenditure changes? The paper goes into some proposed mechanisms. I will keep it brief though, because this is mostly preclinical or animal data.

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Centrally, estrogen acts on the hypothalamus via some ER alpha receptors. This influences thermogenesis, appetite regulation, and spontaneous physical activity. In mice, estrogen supplementation restores spontaneous activity after an overectomy, so getting their ovaries removed like menopause. That's mechanistically interesting for understanding why movement might decline.

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They also discuss brown adipose tissue thermogenesis, or BAT, in estrogen's role in activating UCP1, uncoupling protein 1, and BAT, brown adipose tissue. But in reality, the brown adipose tissue that we hold represents a very small fraction of total body weight in humans, estimated at about 12 grams on average. Not a lot. Even maximally activated studies estimate that BAT contributes somewhere in the range of

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25 to 200 calories a day. It's not nothing, but it's not a game changer, particularly if you're at that lower end. Peripherally, estrogen also supports mitochondrial oxidative capacity in skeletal muscle, promotes lipolysis, and influences the browning of white adipose tissue. bat, the rhizome follicle stimulating hormone may independently affect Beijing and the UCP1 expression. And again, this is all really interesting as how estrogen

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is directly related to this sort of thermogenesis or energy expenditure, but it is just mechanistic at this point. So look, I do think this paper, super interesting, a useful overview of the landscape, but there are genuine limitations. First of all, as I mentioned at the start, it's a narrative review with selective inclusion. It isn't systematic. So this is pulling out interesting information and talking about it.

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rather than looking at the totality of the data. Second, the studies it draws on are mostly small, cross-sectional, and methodologically heterogeneous. So there's just so much going on, small data sets, very difficult to make any conclusions. Some of these groups have as few as seven participants. Third, and it's a big issue, the paper can't cleanly separate menopause from aging. They acknowledge this. Many of the findings that look like a menopause effect disappear when you adjust

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for fat-free mass, and similar declines in metabolic rate are seen in men with aging. That does align with the Ponza paper, which I mentioned earlier, looking at metabolic rate across a lifespan. Fourth, estrogen replacement data is inconsistent. HRT restores some aspects of resting metabolic rate in some studies, but not sleeping metabolic rate and not consistently. That weakens the causal argument.

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and the paper is almost entirely estrogen-focused. It doesn't adequately address the role of progesterone, which, if I've discussed, is likely the primary driver of sleep fragmentation, they themselves identify as metabolically relevant. I do think, though, that the fat oxidation finding from that four-year longitudinal study is compelling, that grant data looking at suppression of the ovaries does give something hosted to causal evidence for an estrogen effect on RMR and physical activity energy expenditure.

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and that that sleep fragmentation pathway is certainly an under-recognized contributor that deserves far more attention, even if the paper itself doesn't really follow that mechanism all the way through. So, stripping back to what is actually actionable, here's my read. And unlike Dr. Mary Claire Haver, I do not think this is the time to throw away your calories, spreadsheets, or stop counting steps. Thought that was, I did not agree with her when she said that on her post. um

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What's probably true is that total daily energy expenditure does decline with age and through the menopausal transition. Fat oxidation may decline modestly and independently of age and physical activity tends to decrease. And a lot of this is mediated by loss of fat-free mass or loss of muscle. But I do think it's overstated that the idea that menopause causes a dramatic metabolic slowdown that makes weight gain inevitable. I don't think that's true.

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The direct hormonal suppression of metabolism is real, but it's a piece of the puzzle, not the whole picture. And reduced fat oxidation, whilst it is real, it does not override energy balance. It might narrow the margin, but isn't this even more reason to keep those calorie counters going? I don't know. If you're into that sort of thing, not everyone has to. So, importantly, the key levers remain. One, preserve and build lean mass. This comes up.

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Over and over in this review, fat-free mass is the strongest predictor of resting metabolic rate and is positively correlated with fat oxidation during exercise. Two, maintain physical activity, I mean all of it. Structured exercise, neat, moderate intensity movement, don't let that behavioral drift happen passively. Three, manage your energy intake appropriately. The playing field may have tilted slightly, so the margins do matter more.

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Keep protein high, it supports lean mass, supports the thermic effect of food, and becomes even more important as you move into your 60s. Four, prioritize sleep. And I don't just mean duration, I mean quality. Fragmentation, consolidated blocks of deep sleep. If you're in perimenopause and your sleep has fallen apart, talk to your doctor about protesterone. Clearly, this is not a recommendation from me because I am not a medical doctor, but it's worth you having a conversation with your medical doctor.

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Progesterone isn't just a hormone replacement consideration. It can restore that consolidated sleep and it can help recover fat oxidation capacity through a pathway that is independent of estrogen. The grant study tells us sleep fragmentation is an independent metabolic variable. The progesterone GABA pathway tells us why it's happening and that's an addressable problem. So hopefully that breakdown made a bit more sense to you and sort of gave you an idea of what we do know.

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what is a lot of hypothesis and interpretation, and what you can do to help support your energy expenditure through the menopausal transition. And you don't just have to accept it as inevitable because these things happen during menopause. There are so many actionable things that you can do that really do just keep things tracking on exactly as you want them to, if you put in that work. Anyway, and work is good, right? Like anything worth doing is worth working for, I reckon. You guys have a great week.

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I'd love to hear what you think or pop the link to the study in the show notes. I'm over on threads, X and Instagram @mikkiwilliden, Facebook @mikkiwillidennutrition. We'll head to my website, mikkiwilliden.com. Scroll right down to the bottom, pop your dates in there from a weekly email. All right guys, you have the best week. See you later.