The Dr Louise Newson Podcast - 20 - Hormones and metabolism: Unlocking the science with Professor Franck Mauvais-Jarvis

Episode Date: August 12, 2025

“I don’t understand why we’re not shouting this from the rooftops, a simple medicine, a natural hormone, that can reduce the risk of both diabetes and breast cancer. That’s incredibly important, isn’t it?”    This week, Dr Louise Newson is joined by Franck Mauvais-Jarvis, Professor of Medicine at Tulane University and an endocrinologist specialising in metabolism.   In this episode, they dive deep into the science behind oestradiol’s crucial role in maintaining a healthy metabolism, reducing inflammation throughout the body, and supporting memory and cognition.  Professor Mauvais-Jarvis explains how improving mitochondrial function, often referred to as the “powerhouse of the cell,” boosts metabolism and helps prevent metabolic diseases such as diabetes. He also highlights the vital, often overlooked role of testosterone in women’s health.  Together they address common misconceptions stemming from the 2002 Women’s Health Initiative (WHI) study and set the record straight on the benefits of body-identical hormones.   Be sure to check out Professor Franck Mauvais-Jarvis’s book, Principles of Precision Hormone Therapy: Healthy Aging and Prevention of Chronic Disease, which presents cutting-edge scientific data and insights from leading experts, including Dr Louise Newson, on the vital role of hormone optimisation in healthy aging.  Available to watch on YouTube We hope you’re enjoying season 2! Share your thoughts with us on the feedback form here and if you enjoyed today's episode, don't forget to leave a 5-star rating on your podcast platform.   We’re delighted to have been nominated in the Listeners’ Choice category for the British Podcast Awards. There’s still time to vote - ⁠click here⁠ Email [e-mail] with suggestions for new guests!    Disclaimer  The information provided in this podcast is for informational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health providers with any questions you may have regarding a medical condition. The views expressed by guests are their own and do not necessarily reflect the views of Dr Louise Newson or the Newson Health Group.       LET'S CONNECT   Website: Dr Louise Newson  Instagram: The Dr Louise Newson Podcast(@drlouisenewsonpodcast) • Instagram photos and videos   LinkedIn: Louise Newson | LinkedIn  YouTube: Dr Louise Newson - YouTube

Some of you might know already, but this podcast has been nominated by the British podcast awards for the listener's choice. So we really need your votes because it would be such an honour and thrill to do well in this. So if you go to the show notes and click on the link, it won't take you long. Please just vote for us. Thank you so much. So on this podcast, I've got a really good friend and colleague, Professor Frank Movae Jarvis, from US. He's a professor of endocrinology with a special interest in metabolism. So we talk a lot about the role of hormones. Easter dial especially, but also testosterone in metabolism,

in reducing incidence of diabetes. And we talk about mitochondria, the powerhouse of ourselves, and how that can improve in the presence of Easter dial. So enjoy it. So, Frank, it's really exciting. I feel like I've known you for quite a long time, but I can't remember when I first, I think I reached out to you, didn't I, because I'd read one of your great papers.

It was at the beginning of COVID. Yeah, and in fact, I was reading a paper the other night, and I read it out to my husband, the line, because it was saying, there is good evidence that estrogen protected people from COVID. And I was saying to him, why wasn't anyone listening at the time? Like, it was so frustrating. But what I love about your work is that you're interested in the metabolic processes that occur in the body.

And there are very few people, really, I think, that understand the importance of hormones, eustodial progesterone and testosterone, on improving our metabolism and reducing inflammation. So can you just tell me a bit about your background and why you're doing what you're doing a bit about the research that you've done for so many years? I'm an endocrinologist.

I trained in internal men. medicine and endocrinology in hospitals of Paris and France. It's a complicated story. I moved to the U.S. to do a postdoctoral fellowship to study metabolism, you know. And I was at the Jocelyn Diabetes Center and Harvard Medical School with Ron Khan. It was actually one of the best lab to go at the time. But let's say right now I am an endocrinologist. I take care of menopausea women and testosterone deficient men.

at the Veterans Medical Center in New Orleans. But I'm also leading a research lab on estrogen, progesterone, and testosterone in metabolism. I'm also a director of an NIH-supported Center of Excellence in Sex-Based Precision Medicine at Tulane University, School of Medicine. And I'm professor of medicine at Toulay. So that's where we stand now. They asked me why did they got interested into that?

You know, it's a very long story. My father, when I was a kid, was a reproductive endocrinologist. In France, he actually was one of those who helped develop estrogen gel. The gel a woman put on their skin. And the story of nobody knows. is that he was working on the percutaneous absorption of steroids. And he used astrodial, tritiated, you know, radioactive astrodial, brought the cream home one night, and he put it on the skin of my mother, and then he collected her urine, and he found

radioactivity. That's what in 1969. Nineteen sixty-nine. One of the first evidence that, um, that, um, one of the first evidence that, um, steroid hormone, we're going through the skin. Amazing. But I'm confused because that's 1969 and that was Easterdial. But around that time, it was all conjugated equineostogens.

It was the pregnant horses urine or it was ethanol estradiol. So certainly in the UK and US, that was the go-to prescription for HRT. I know it was slightly different in the continent. But why were people not thinking, more about Easter dial? Well, it was in 1969 that he did this experiment, but estrogen was developed in France in 1986. So the question why, well, you know, when I went to medical school and when I did my

clinical training andocrinology in Paris, I never heard of conjugate de equinextricis. We were prescribing body identical hormones, you know, astrodial progesterone and testosterone. And I actually heard the first time about, I mean, I heard, I knew what it was, but I heard the first time about CEE and medoxy progesterone acetate during the earthquake of 2002, you know, the Women's Health Initiative trial report by the media and by JAMA,

the hysterical report of the WHOHI. You know, me, I was not surprised. I was surprised because we were prescribing other types of hormones. And so I was increduled from the beginning. Well, it was so wrong because then they made a blanket decision that all hormones were bad. And I was reading the role. report recently where they decided that they should label hormones as carcinogens. So all types

of estrogen were labeled then as carcinogenic, so as in causing cancer as a result of that study. But that wasn't the same as eustodial or progesterone. I mean, the biggest concern really from the WHOHI, the Women's Health Initiative study, was the mojoxyprogesterone acetate, which is the synthetic progestogen, wasn't it? First of all, estrogen are not carcinogen because we know today. Actually, they knew it from the beginning during the WHO. The arm in women without a uterus, the arm with conjugated estrogen alone, there was already a 30% decrease risk of breast cancer.

And today we know, because there are lots of studies that have been done and there's a recent meta-analysis. showing that CEE or estradiol alone in women with other uterus clearly significantly protect from breast cancer. When you add a progestogen and especially a synthetic progestogen like midoxyprogestero and acetate, then at the time of the WHOHI, that's when you had a signal, a small increase of breast cancer. But if you think about the absolute risk, it was one or two or two women out of 10,000. So that's a very minimal risk.

And first of all, it was not even significant. But today, if we look at the data, there is still a minor increase risk. It's not always significant when a progestogen is added to any type of estrogen. and there is especially a minor risk if it's a synthetic progestergen. And probably the reason is that estradiol increases the expression of the progesterone receptor. And when you have progesterogen on that, it may in certain circumstances increase the risk, but this is a very, very minor increase risk, you know. if you compare it with what happens when you don't take hormones.

Absolutely. And that is a big difference, actually, when you're comparing the risks of not having hormones. And, you know, I'm a physician, not a gynecologist, as you know, and I'm very interested in the immune-regulating effects of hormones, so how we can reduce inflammation in our body, how we can improve our metabolism in our bodies and reduce future risk of diseases

including diabetes, which we know is far more prevalent than ever before, really. But we've known, even from the WHOI actually, looking at diabetes, there's a lower incidence of diabetes in women who take hormones. And there's a better sugar, you know, glucose control as well. And I've seen quite a few patients who have type 1 or type 2 diabetes, and their diabetes control has just become haywire when they've become. perimenopausal, and then they have the hormones back. But it's all three hormones can affect metabolism in a beneficial way. But I don't know why we're not shouting from the rooftops about

this, because to have a simple medicine that's a natural hormone, reducing risk of diabetes as well as breast cancer, but, you know, just looking at metabolic effects with diabetes, that's really important, isn't it? It is, right. And in fact, In fact, it's one of the poorly reported the effect of estrogens in the Women's Health Initiative. If you look at the data, there was at five years a 25% decrease risk of diabetes. And if you continued after the follow up 13 years, there was even a greater decrease risk of diabetes. So the decreased risk of diabetes with estrogen alone, and even estrogen with progestin, was as powerful as the effect in preventing fractures.

Nobody speaks about that. And it's been reproduced a lot of other trials because astrodial has several beneficial effects. It improves insulin sensitivity. It decreases visceral fat. It improves insulin production. And like you said before, it decreases inflammation. And all that is very important for glucose homostasis.

overall, the insulin resistance, when you measure that by Homa, is improved by about 30%. But what is interesting is that it's the effect, and it works in diabetic women, of course, but the improvement in insulin sensitivity and the prevention of diabetes works in non-diabic women. And the effect is stronger with oral estradiol because, than transdermal, because of the first past liver metabolism. So when you give oral astrodial, you have a greater, so you shower the liver through a portal vein and you have a greater suppression of hepatic glucose production. It's the same reason why oral astrodial.

has a greater effect on lowering LDL cholesterol and increasing HDL cholesterol than transdermal because of that first-past liver metabolism. And this is very interesting, and I just want to sort of elaborate a little bit because there's a lot of confusion between tablet estrogen because people think about risks with tablet. But it's very different when you ingest ethanol estradiol to estradiol,

because ethanol estradiol is a chemical, it's got an ethanol bit added to it. And so when it goes into the liver, it will activate clotting factors. It will work very differently in the liver rather than the pure estradiol. And I don't know what it's like in the US, but in the UK, there's only one contraceptive that contains estradiol. All the others are ethanol estradiol, whereas most doctors will just say it's estrogen and they won't know the difference. And metabolically, this is really, really important, actually. Yes, and the risk, DVD, you know, the risk of blood clot, deep venous trombosis with oral astrolio is very minimal.

In any women, without taking any estrogen, the risk is about between 1 and 3 out of 100,000. Yeah. And on oral estrogen, whatever the estrogen is, it's about, three to 15. So that would be three times more. But it's still very, very little, you know. But that's all over the board, all estrogens. The risk with our estradiol is very minimal.

And especially, you know, it's always the same thing. People mix all women in the same bag. But it's not, this is not precision medicine, you know? Yeah. You know, if you take women who are healthy, who are not obese, who don't have any history of blood clots, I mean, they can take oral estrogen without a problem. Of course, if somebody has a history of blood clots, is obese, is sedentary,

and has hypertensional things, you would pay more attention. But still, the risk with CEE compared to conjugated estrogen compared with astrodial, ethynal estrodial is 100 times more potent than estradiol. It's not the same molecule. Yeah. It's very important to distinguish between the difference. And, you know, when you talk about precision medicine, it's really important because as a clinician, of course, I want to use the evidence in the science, but I want to individualize care for

patients. And we've known for decades that different women often need different drugs. doses to improve their symptom control and also their future health. And we've known this with oral and transdermal medication. And we spend a lot of the time in the clinic working out the best formulation, the best dose, but also whether patches, gels, tablets, or sometimes a combination. And that really, really can vary between patients, can't it?

And actually, it takes me to another problem of the current. recommendations is that we, it is not recommended that you measure estuarial levels and women. I know you do because you're a forward thinking and a modern physician, but it's not recommended that you measure astralial level in women. So basically what is recommended is to consider the treatment is efficient if hot flashes are corrected. But it doesn't tell you if you have a serum, a concentration of astrodial that are therapeutic for osteopolis. And all studies have shown that

you needed about 80 to 100 picogram per ML minimum to prevent osteoporosis 100%. And usually when you use gels or patches, you don't know where you are. And very often, you're below 60 picogram per ML. So you may protect hot flashes, which is already good. You don't know if you have enough astrodial to prevent osteoporosis. Yeah.

So why would we not measure estradiol level to supplement women, but we measure testosterone level when we supplement men? What does it mean? It makes no sense, does it? And I think there's two things that are really interesting in that. Firstly, is that any test we do in medicine is a guide, and it has. helps us, but it has to be in clinical context as well. I saw someone yesterday in my clinic whose level of Easter dial was really high and it didn't fit in with the clinical situation. And I said to her, did you use your gel in the morning of the test? She said, oh yes, I rubbed it all down my arm. Oh, perhaps I shouldn't have done that. So it was probably a contaminated sample

and we'll just do it again when she hasn't rubbed it over where the needle went in. But also there was another patient of mine over here. It's very unusual, but it's been really warm, Frank, which, and a lot of patches aren't sticking on very well. And so one of my patients has been very worried about her mental health. She's taken a real dip in her mental health. And I spoke to her and she was getting worsening migraines as well. And she said, but I've not changed anything. Everything is the same. I don't understand. And taking a clearer history, she was also having some urinary symptoms. She was having some muscle and joint pains. and she was having some palpitations,

but she thought they weren't significant to tell me it was only when I asked her. And then I got her to show me the patches and they were bubbling and lifting. And so this inadequate or suboptimal absorption of the eustodial was triggering her symptoms, but it was worse, actually, because it was intermittent.

So I'm sure at nighttime, when it's cooler, they were absorbing better. And as you know, a lot of people have worsening symptoms when their hormones are changing and fluctuating. It's not just the absolute levels. So we really need to think about that. But the other part, when you talk about testosterone levels in men, it absolutely makes sense and the same in women.

But I just wanted to ask you something because I don't want to be rude about your age, Frank, but, you know, we're both quite old. And we would have done our medical training basing all the studies on the treatment we give on men, it's usually was a 70 kilogram man, wasn't it, that the research was done when we think about medication for diabetes, for hypertension, for antibiotic dosing,

everything is always based on a 70 kilogram man. Luckily, the year actually I graduated in 94 was the first year that people started to realize women should be included in studies, which is great. But somehow, when it comes to testosterone for women, we're not allowed to look at the male studies. So when I say that testosterone can reduce incidence of diabetes,

hypertension, cardiovascular disease, dementia, because we have good evidence for men, I'm told but Louise, we don't have the studies of women, therefore we can't use it for women and tell them about these benefits. And it feels a bit not fair, really, because it's one medicine that we're not allowed to look at the men's data. The Undercrant Society say, you know, it should be approved only for a hypoxxual desire. But testosterone at any time in a woman's life, especially, you know, during reproductive years,

is 50 times more abundant than estrogen. So do you think that a hormone that is 50 times most abundant, it's actually the most abundant active sex theory? I don't think it's only for libido or sexual desire. It is for metabolism. It is an important metabolic hormone. And actually, there are studies. There are studies, a small, randomized trial and other type of interventional studies

that show that, first of all, it increased lean mass in women. Second, it increased bone mass on top. studies that were done in menopausal women, it increases bone mass on top of astrolideal effect, and it even helped women with cardiac failure to have a better oxygenation. So, yes, I think it's clear that testosterone is important to women. And actually, animal studies, it's always important to look at animal studies, to confirm and understand what we cannot go deep enough in humans. But in animal studies, it clearly shows that both estrogen via estrogen receptor alpha

and testosterone and dh-ht via the antigen receptor are necessary for bone. They don't work on the same thing. One works on cortical bone, the other works on a trabecular bone. So they are both synergizing. I personally give testosterone to any women that I see if she wants it. I measure the concentration in the serum. And I try to put it at the upper limit of the female concentration. Let's say testosterone in women is between 20 and 80 and 70 nanogram per d.

I try to put women at 8,100, which would be a very severely hypogynetal men. And I think I follow about a hundred women on testosterone. I haven't heard about any women tell me that she developed a beard, that her voice changed, that she had acne, or that her clitoris was increasing in size. I never heard of that. No, I mean, we have thousands of women use testosterone, and we've got data for nearly 10 years now. And we do not have bearded patients.

You know, they don't shave their faces. But actually, even if it caused side effects, I would still as a menopause or women want to take it because testosterone has transformed my brain. It's enabled me to continue working. It's enabled me to exercise. It's enabled me to sleep. It's enabled me to just be an independent person.

So even if I was getting side effects, as a patient I'm allowed to choose and I can balance benefits versus risks. But, you know, we hear all the time that women have just refused it for the wrong reasons and they're often given antidepressants or antipsychotics and we see a lot of women on antipsychotics that have actually very negative metabolic consequences.

We know antipsychotics can increase risk of hypertension, diabetes, osteophrosis and, you know, reduce. sexual function as well. So it's even worse, actually, for a lot of these people. And probably, and when I say probably, I mean, what the studies suggest is that because testosterone in women at, you know, women physiological dose, high physiological dose for women. The reason why testosterone is important is that by increasing muscle mass, it actually decreases fat mass. So the effect on fact is probably dependent on the effect on muscle.

Absolutely. And I really agree. So just before we end, I just wanted to thank you publicly actually because you invited me to co-author two chapters of your book, which has just come out. It's a really amazing book and I can't wait to read the rest. You've had the pleasure of reading at all. But can you just tell us a little bit about the book

and why you wanted to do it? So it's a book about precision hormone therapy, which obviously includes a large first part on menopausal hormone therapy, every aspect of menopausal therapy from private practice to academic practice, breast cancer, progestogens, diabetes, cognition, etc. there's also, of course, a very important part on testosterone therapy. But, you know, precision hormone therapy is also important with regard to thyroid hormone therapy and growth hormone therapy.

So it's really about the bioidentical hormones, which are very important to maintain health span. You know, it's not going to increase our lifespan, but. It is clearly improving the health span. So they are anti-aging hormones. Whatever they say, the data, the science is there. They are anti-aging hormones. That's why I wanted to, you know, collect a group of experts and edit that book. And that's why I wanted to have you in the book.

Well, it was great. And it was lovely to be able to write about the role of the immune system, but also mitochondria. and how important mitochondrial function is for our health, but how our hormones, all three, estradiol, progesterine, have really key roles in mitochondrial function. So the book is written more for doctors and healthcare professionals, but I think there's a lot of public people,

as in non-health care professionals, that will really enjoy it because it's very evidence-based, it's very well-referenced, and there's a lot of information that people will want, to read and understand from it, I think. You know, you just said something very important that I think we should say a few words about is the importance of estrogen in mitochondria.

And, you know, I think, evolutionary speaking, that's what estrogens were designed to do. Because the ancestral estrogen receptor evolved 500 million years ago, approximately, before any other sterile receptor, before the stress hormone receptor, before anything. And it evolved in mollusks and analids, you know, warms. These animals, they didn't have sexual reproduction.

So the reason why there was an estrogen receptor there and there was not even estrogen, is that probably they were using phytohestrogen, environmental estrogen, to bind a receptor, and to protect survival and to promote energy and to protect the mitochondria. Because one of the very important thing we know today is that mitochondrial function is geared toward women, metabolism.

Mitochondria and women are much more functional, have less mitochondrial DNA damage, less oxidative stress and better function than mitochondrial men. And why? Because women have higher level. of astrodial. Not only they transmit the mitochondria, but they have a high level of

estrogen to protect the mitochondria. So I think estrogen are very important for mitochondria. But testosterone in men is a reservoir of astrodial. And most of the beneficial effect of testosterone in men,

apart from muscle mass, are mediated via estrogen to estrogen, to estrogen, including erection and libido. Yeah. So we should be doing more studies in men about the importance of eustodial in the metabolism and longevity and mitochondrial function of men, because men get really freaked out when I say to them

that they've got more eustodial in their body often than menopals or women who don't take hormones. I see a lot of men who come when I put them on testosterone and tell me, oh, doctor, you know, I have a high level of the female hormone. I have to explain to them, it's not a female hormone. And I also see men who come treated by some outside doctors in women's health clinic who put them on testosterone with an aromatase inhibitor. Basically, they eliminate all the beneficial effects on testosterone, especially in vessels, because men with aromatase mutation who do not make astrolideal,

they die of a heart attack soon. Not only they have osteoporosis, but they die of heart attack. I have to explain to them, listen, it's not a female hormone. Without estrogen, you wouldn't have a hard-on. I tell them exactly like this. They never ask me the question again. They understand. Yeah, it's so important.

I could listen to you forever. Before we end, I always ask for three sort of take-home tips, learning tips. So I'd really like to ask you three ways that estradiol can improve metabolism in men and women, what are the three key things that you think are most important about the metabolic effects of estradiol? One thing is the effect on mitochondria. If you improve mitochondria, the powerhouse of the cell, you improve metabolism, and you prevent metabolic dysfunction.

So I think it's the most important thing. Then there is, like you said, a very important effect on the immune system and a prevention of inflammation. And then if I had to choose the third one, I think it would be the brain cognition. But there are lots of other effects because basically

Australia works on every single organ and cell. It's amazing. It's so important yet it's been neglected for so long. So, well, thank you so much. And hopefully I'm coming out to America at some stage soon. But thank

you so much for your time. I've really enjoyed it. Thank you. It was my pleasure to be here.