2. Hormones

Episode 4 Hormones

 In this episode, Dr. Gordon discusses female hormones. She gives us a glimpse into their function and what happens to aging women as they lose those hormones in menopause. She also talks about the skillful use of hormone replacement to extend life and enhance its quality. For those women who don’t or can’t take the typical form of hormone replacement therapy,  she describes workarounds for benefit of both brain and bone health.

Links to references and more reading on some of the topics mentioned:

1.  Increased Alzheimer’s Risk During the Menopause Transition

2.  Mercury and Lead toxicity in menopause-induced osteopenia

3.  Estrogen receptors are complicated, we'll address in a future episode, but here's a brief, layman's terms summary.

4.  Comprehensive genetics testing provider, IntellxxDNA

5.  Hormone replacement therapy  prescribed for women aged 57-82 was associated with a significant improvement in tests of cognitive function at 24 months.   

6.  Testing estrogen metabolites in the urine.   

7.  Foods included in a conventional Polish diet—cabbage and sauerkraut—are associated with a reduced risk of breast cancer in Polish migrant workers.

8.   Genistein can confer protection against bone loss  and is emerging as a therapeutic option against the pathogenesis of memory impairment.  

Dawn Lemanne, MD
Oregon Integrative Oncology
Leave no stone unturned.

Deborah Gordon, MD
Northwest Wellness and Memory Center
Building Healthy Brains

Chapters

• 1:38 Increased Alzheimer's risk in women
• 8:55 Estrogen receptors in brain and bone
• 16:30 Hormone prescriptions in perimenopause and beyond
• 29:57 More about HRT in older women, later in life
• 33:13 genistein (originally from soy) as an alternative to estradiol therapy

Transcript

[00:00:59.250] - Introduction

In this episode, Dr. Gordon discusses female hormones. She gives us a glimpse into their function and what happens to aging women as they lose those hormones in menopause. She also talks about the skillful use of hormone replacement to extend life and enhance its quality. And luckily, she says, there are workarounds for those who don't take hormones. I know. One of the things that you've told me and taught me is that hormones are no joke when it comes to brain aging. And you've just gave me a scary article. Let's see, the title was I have it right here. Increased Alzheimer's risk during the menopause transition. A three year longitudinal brain imaging study. And this study took pictures of the brain in women at various points along the menopause continuum. And it was some pretty scary stuff. There it is. Trouble sleeping after I read that last night.

00:01:38 Increased Alzheimer’s Risk During the Menopause Transition 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291073/ 

[00:01:59.030] - Dr. Gordon

But I think it's important to understand that. And then it's important to say there are a couple workarounds for that. And this interest in this field has really been stimulated by the observation that if you look around the world and if you look around the United States, two thirds of Alzheimer's patients are women. Two thirds.

[00:02:20.930] -Dr. Lemanne

But aren't there a lot more older women than there are older men?

[00:02:23.860] - Dr. Gordon

But if you take all 70 year old women, all 70 year old people with Alzheimer's, two thirds of them are women.

[00:02:30.030] -Dr. Lemanne

Got it?

[00:02:31.170] - Dr. Gordon

Age independent. But for the things separate from hormones that have been credited for this preponderance in women of Alzheimer's disease, now, interestingly, two thirds of caregivers for Alzheimer's are also women. So women are pretty tied up in Alzheimer's disease. For a long time, it was thought that it was age that we outlive men, and so that's why we get more Alzheimer's disease. And that's been discredited by doing age specific studies. But the other thought has been, you know what? I feel some kindly old patronizing gentleman is saying, yes, but, honey, far more of the men are doing the cognitive things that we know protect you from Alzheimer's. Greater years of higher education. I think that's no longer true. But then also greater years of working outside the home in something that might be cognitively demanding on any level. Even if you're working at a very rote job. You're interacting with unexpected people, which is always a good thing for your brain. Unexpected tasks. If you're taking care of the kids at home, that's demanding in one way. But years outside the home, laboring, being paid for labor outside the home, more years doing that is correlated with better brain health.

[00:03:49.710] - Dr. Gordon

It was kind of attributed to that.

[00:03:51.340] -Dr. Lemanne

But now we have staying at home is bad. Being out of the house is good in terms of brain aging and brain, yes. But even in the reason for the.

[00:03:59.320] - Dr. Gordon

Male female difference, that was accredited for that. But that's been discredited as well, because, of course, now we have a lot more women in the workplace, and even in women who've been in the workplace, two thirds of those Alzheimer's patients are women. And so I think that the buck really gets passed from we live longer to they work harder than we do to we're in trouble if we lose estrogen.

[00:04:24.590] -Dr. Lemanne

So it's hormones. It's hormones. Okay. Well, this study that you gave me was very clear in the findings that PET scanning and other types of imaging show brain changes that happen right at menopause. And these brain changes are quite frightening.

[00:04:41.570] - Dr. Gordon

They're pretty dramatic. And the cognitive decline didn't exactly parallel the more alarming and earlier declines in glucose utilization we saw in the brain. The actual cognitive delay comes later than the PET imaging changes. One of the observations we make with Alzheimer's is that the disease starts 20 years before it's diagnosed.

[00:05:03.100] -Dr. Lemanne

So these scans show a problem long before the patient exhibits any symptoms or signs of cognitive difficulties.

[00:05:10.440] - Dr. Gordon

Exactly, because I think some of the greatest changes were in the perimenopause areas on those scans. But your brain will learn up to a point to use an alternate fuel. Those scans showed the brain's decreasing ability or activity of using glucose for fuel. It wasn't doing it so well, but the brain will switch and use ketones.

[00:05:35.890] -Dr. Lemanne

Ketones, I think, for our audience, are the byproduct of fat breakdown for fuel. Is that correct?

[00:05:41.180] - Dr. Gordon

Yes. So the way I explain it to patients who I'm trying to prevail upon to go on a ketogenic diet for various reasons, not everybody, but for some people is if you want to run across the parking lot, you can fuel your muscles with the meat in the hamburger and the cheese on top of it and the bun that it's wrapped in. The protein for the muscle repair, the fat and the carbohydrate for running across the parking lot. But if you want to think and strategize about the cars coming, you can use the carbohydrates in the bun. But as the older you get, those don't get into anybody's brain as well as they did when we were younger. And fat is a gigantic molecule that cannot cross the blood brain barrier, even a leaky blood brain barrier. So our brains are our body's most precious organ. When you're young, and if you're exposed to a toxin, your body will wisely say, this cannot get to Dawn's brain. That's her most vital organ. I'm going to lock it up in her bones. I'm going to lock this mercury from the industry that her family lives near, or I'm going to lock up the lead that Deborah was drinking water from lead pipes when she was young.

[00:06:53.120] - Dr. Gordon

I'm going to lock it up in her bone because I don't want it to get to her brain while it's circulating in her body. I have this nice barrier that's called a blood brain barrier. So big molecules can't get in ther. As we get older and as we lose estrogen, it's not just affecting the brain, but it causes osteopenia or osteoporosis or thinning of the bones. There is actually medical literature about mercury and lead toxicity arising from the development of osteopenia and osteoporosis in menopausal women.

00:07:20      Mercury toxicity in menopause https://pubmed.ncbi.nlm.nih.gov/22205147/  

and lead   https://academic.oup.com/aje/article/160/9/901/86517  

[00:07:25.420] -Dr. Lemanne

So there's a two pronged issue with estrogen. It's not just the brain directly. It's all these other organs that are doing things that protect the brain.

[00:07:34.710] - Dr. Gordon

Exactly.

[00:07:35.590] -Dr. Lemanne

Okay, so if you take the average.

[00:07:39.510] - Dr. Gordon

Man or woman on the street and they start not being able to get as much glucose into their brain, their body will work a little harder to burn fat and make ketones so that their brain can be fed. Our livers are where we primarily do this. Our livers can only make ketones when our insulin levels are not too high. Insulin blocks fat burning and the production of ketones. So what's one of the main problems in modern world middle aged people is increasing belly fat, insulin resistance, type two diabetes. Those people lose the ability because their insulin levels are too high to adequately substitute ketones for their glucose, which is not getting into their brain.

[00:08:31.470] -Dr. Lemanne

So you're talking about insulin resistance in the body other than the brain. But it sounds as though there's some issue with glucose uptake, and therefore insulin sensitivity in the brain itself with aging is that caused by menopause, by a decrease in estrogen?

[00:08:55] - Dr. Gordon

It contributes to it.  So there are estrogen receptors in the brain that are slightly different from the estrogen receptors in the body, 

00:09:00  Note:    In a “mikes muted” aside, we realized there is an abundance of information about estrogen receptors, specifically sorting out their effects on aging bodies and brains and the intersection with the age-related effects on cancer risk.  Stay tuned for a complete discussion in an upcoming podcast, but meanwhile, here are some estrogen receptor details:  

Throughout the body there are two main types of estrogen receptors, ER alpha and ER Beta.  How your estrogen receptors behave, how they respond to estrogen, is programmed by your genes.  ER alpha is managed by the ESR1 gene.  Staying logical, ER beta behavior is encoded by the ESR 2 gene.

https://en.wikipedia.org/wiki/Estrogen_receptor_alpha#:~:text=In%20humans%2C%20ER%CE%B1%20is%20encoded,ESR1%20(EStrogen%20Receptor%201).

Just to make matters complicated there is a 3rd type of estrogen receptor in the brain, but it is NOT #3 it is GPER1, so let’s just forget about that.

In any discussion of estrogen, you’ll see that there are also 3 types of estrogen, also #’d E1, E2, and E3.  For brain health, we’re looking essentially at E2, aka estradiol, and the form of estrogen available in bio-identical formulations (pharmaceutical or compounded) that properly replace the estrogen primarily lost at menopause (E2, estradiol)  

00:09:00 Dr. Gordon continues… but there are estrogen receptors that are activated both to create fuel for the brain and to enhance synapses--so the connections between the nerve cells in the brain--their vitality and well-being, is enhanced by estrogen, the development of the neuron cells themselves and their currency, which is hopefully glucose as long as we have it and need some of it, but then primarily more ketones. So people are different because it's a little bit genetically determined. So one woman might have estrogen receptors. They're really fine, and they're kind of sturdy, and you can kind of do with them or do without them. I happen to have variants in two genes that relate to my estrogen receptors, showing that there are parts of my brain that will function a lot better if I activate those estrogen receptors and do so in all the ways you just said better use of both glucose and ketones as fuel. And what I just said, keeping the nerves themselves healthy and the connections between the nerves healthy. So we've known that for a long time now.

[00:10:06.550] -Dr. Lemanne

Are these tests that people can get the type of estrogen receptor you've mentioned, is that available, for instance, on 23 and me?

[00:10:14.690] - Dr. Gordon

Some of those genes might be on 23 and me, but a colleague of mine who started a company called 

00:10:30 Genetic testing through Intellxx DNA https://www.intellxxdna.com/

and they do their own collecting of the sample and they analyze genetic variants and they categorize them by category. So what I was looking at this morning, because I knew we were going to talk about it, were my cognition genes and my estradiol genes. And then, oh, I'm always interested in my homocysteine genes and I might be looking at my melanoma genes because those all look so good. It's nice to see a whole area where I don't feel like I'm at any genetic risk.

[00:10:48.910] -Dr. Lemanne

Yes, it's nice to look at those, isn't it?

[00:10:50.740] - Dr. Gordon

I think that's the most reliable and that's kind of the Cadillac version of genetic testing, because her report said to me, you have a variant in this estrogen receptor, and this is a commonly available estrogen receptor gene. It is done in 23 and me, but not routinely done in blood tests like some other genes are. So this estrogen receptor gene, she not only tells me I have a variant of it, there's a list of what are the clinical implications of having that and then what are the research based interventions and even food sources and dosages and prescription strategies of the ways to address that variant. And the thing that's nice about these estrogen receptor genes that we're talking about in the brain and much as I think hormone replacement therapy is an important strategy that every woman should consider going into menopause for the well being of every part of her body, not just her brain. The estrogen receptors in the brain and very handily, the ones in the bone. And remember I said it's when your bone softens in menopause, because you lose estrogen, that you get mercury or lead toxicity. Those sets of estrogen receptors can be stimulated by supplements, and not just by estradiol.

[00:12:16.750] -Dr. Lemanne

Over the counter supplements.

[00:12:18.070] - Dr. Gordon

Over the counter supplements that you don't.

[00:12:19.630] -Dr. Lemanne

Need a prescription for.

[00:12:20.490] - Dr. Gordon

That you don't need a prescription for. I want to say something. We've sort of bandied about and interchangeably estrogen and then I just dropped the word estradiol and that's a prescription. Yeah, right. But estrogens are a category, the female hormone, and it comes in three forms. Even in menopause with no replacement therapy, a woman will still make some estrogen from her, primarily her adrenal glands, and that's called E1, or estrone. And it's the naughty estrogen, it's the more carcinogenic, it doesn't activate these receptors that we’re cherishing and wanting to stimulate in menopause. E2 is estradiol, which is now the hormone they're using for hormone replacement therapy. And it's the predominant hormone during our years of fertility.

[00:13:14.050] -Dr. Lemanne

So that's the main one made by the ovaries.

[00:13:16.450] - Dr. Gordon

Yes, that's the main one made by the ovaries.

[00:13:20.370] -Dr. Lemanne

And estrone Is made by the adrenal glands.

[00:13:22.100] - Dr. Gordon

And then the last one is estriole. And I'm actually not I think, well, estriol is made by metabolism from the other estrogens, and it's the primary estrogen made in pregnancy.

[00:13:31.790] -Dr. Lemanne

Okay. Is that e three?

[00:13:33.120] - Dr. Gordon

That's e three. Right. A little aside, there's another place estradiol is made, which is in the abdomen of fat people. So I test a menopausal woman at the age of 55 perimenopausal, and she says, oh, look, I've still got a little of estrogen. It measures 20, and that's in picograms per milliliter. And I sit back and I say, did you see that man in the waiting room who has a slightly protruding belly? I bet his estrogen is 40. And you probably know why. Because of in the realm of breast cancer.

[00:14:07.570] -Dr. Lemanne

Right. Aromatase.

[00:14:09.090] - Dr. Gordon

Aromatase. So abdominal fat can turn testosterone into estradiol.

[00:14:14.470] -Dr. Lemanne

Now we're talking about deep visceral fat, not the subcutaneous.

[00:14:18.410] - Dr. Gordon

Yeah, okay.

[00:14:19.480] -Dr. Lemanne

Love handles are good for us.

[00:14:20.740] - Dr. Gordon

Yeah, it's a little cushion in case I ever get deathly ill and can't eat for two weeks. Oh, that's my cushion. People live longer who have a little subcutaneous fat when faced with adversity. I should say so. Surviving a hospitalization.

[00:14:34.610] -Dr. Lemanne

So that's your lunch box?

[00:14:35.940] - Dr. Gordon

That's my lunch.

[00:14:36.970] -Dr. Lemanne

Okay. When you talked about progesterone, I've read a little bit about this in Brain Injury, how progesterone, even in males yes. Can help with recovery of cognition and brain damage. How does that fit into the estrogen picture?

[00:14:52.570] - Dr. Gordon

Well, the primary reason we use progesterone in the estradiol hormone replacement picture is and for a long time, we didn't estrogen therapy has gone through multiple incarnations over the last half century, and one of them was estrogen is the fountain of youth. Just give every woman estrogen and oh, dear. Nasty little detail, which is about 10% of women develop endometrial cancer if they only have estrogen.

[00:15:17.040] -Dr. Lemanne

10%.

[00:15:18.340] - Dr. Gordon

I think it's actually more than that. It is pretty significant. So now we always give progesterone in some form or another to every woman who's receiving estradiol for hormone replacement therapy.

[00:15:33.220] -Dr. Lemanne

Now, does this make women who are older keep their menstrual cycles going? Do they bleed?

[00:15:38.260] - Dr. Gordon

Women in a cycling hormonal situation might bleed, but it's not a menstrual bleed. So, for instance, when you are a young woman and you take birth control pills and they give you fake ones the last week of the month, I don't even think they use that kind anymore. But when I was young, that's what they did. They say, oh, you still got your period. That's not a period. A period is the result of an estrogen surge in the first part of the month that yields ovulation and a progesterone surge with the estrogen in the second part of the month. And when that all gives up because there's no pregnancy, then you have what's really a menstruation. If you just gash my uterus and it bleeds, that's just a bleed. If you just give a senile uterus estrogen and progesterone and then stop it, it'll bleed because it was a little fluffed up for a while. But it's not a true period.

[00:16:27.680] -Dr. Lemanne

So the true period has to do with ovulation?

[00:16:30.210] - Dr. Gordon

Yes.

[00:16:30.830] -Dr. Lemanne

Okay. So there's no ovulation happening in older women who are on hormone replacement therapy. We're not talking about needing birth control and things like that.

[00:16:38.930] - Dr. Gordon

Women in the perimenopause, you might want to check and be sure because, of course, everybody has a distant relative in their family who had a baby when she was 52 or has an apostle story. There you go. So if somebody in your family came into me and said they haven't had a period for a while, but we measure a different hormone called follicle stimulating hormone, which is the one that provokes that ovulation that results in pregnancy. If that's very high, you're in menopause. If it's lower, meaning it's not going all out trying to get the body to listen to it. That's why it gets very high in menopause because the ovaries don't respond. Follicle stimulating hormone is screaming at the ovaries, ovulate, they're gone. They can't do anything anymore.

[00:17:27.640] -Dr. Lemanne

They can't do it.

[00:17:28.400] - Dr. Gordon

It's when it's really high, then you don't need birth control even though you're starting on hormone replacement therapy maybe just a year after you've stopped having your period and you're not that old. You're only 48 or something like that.

[00:17:42.550] -Dr. Lemanne

Walk me through this. So say a woman is perimenopausal. Does she come to you and get her estrogen receptor genetic variants tested?

[00:17:50.910] - Dr. Gordon

I would say I use the estrogen receptor variant knowledge as background information. And for me, the argument is so strong for using hormones. If you can tolerate them and you don't have adverse reactions or a phobia about them or feel badly when you take them, I think they're so good. So, for instance, a woman in her late 40s came to see me recently because she had shooting high blood pressure and terrible headaches with CrossFit type exercise that she had never had before. And she got the full workup from somebody more knowledgeable than I about rena vascular hypertensive sources for all that. But she was 48 and she was still menstruating, so they didn't look at her hormones. But she told me also she was having night sweats and hot flashes and her FSH was high. Her pituitary gland was yelling at her ovaries, suggesting she's in menopause. Her estrogen levels were kind of as big as a fat man in the waiting room. Not that high. And she was somebody who clearly had higher estrogen levels a woman going through her menstrual cycle will vary between levels of 50 to 250 or 300. So we were happy with 50 achieved through hormone replacement therapy.

[00:19:04.490] - Dr. Gordon

But a 48 year old woman who's still very voluptuous and having periods shouldn't be having an estradiol level of 50, even if that's not pathologically low. So I checked her FSH, her estradiol, her progesterone, because perimenopause can be disorders in either estrogen or progesterone. And we started replacing them, and her headaches pretty much went away, and her blood pressure responded much more readily to a minor intervention rather than multiple drugs that weren't helping. And she's back exercising at CrossFit full force.

[00:19:43.290] -Dr. Lemanne

So will you continue this? Will you change things as she ages? How does this look as she continues on and goes through the actual pause? In a few years as she actually.

[00:19:53.380] - Dr. Gordon

Gets older, she might need an adjustment of her doses. And I've been treating women with hormone replacement therapy for about 40 years, and it's been greatly more elaborated than when I started with compounding medicines that were harder to get. Let me back up a little bit and say the answer to the question of what I'm going to do with her as she ages. The broad answer, which is whether a woman is in her mid 40s doing perimenopause or in her early 80s, is the latest I've done and the latest that's been studied in clinical research. 

00:20:38 Estradiol prescribed for women aged 57-82 were associated with a significant improvement in tests of cognitive function at 24 months.  https://journals.lww.com/menopausejournal/Abstract/2018/08000/Menopausal_hormone_therapy_and_mild_cognitive.5.aspx  

And they want or I suggest they might try, stretch of hormone replacement therapy to see if it works for them.

[00:20:34.460] -Dr. Lemanne

So what are you looking for in.

[00:20:36.040] - Dr. Gordon

The 87 year old woman that I gave it to? I was looking that it perks up her brain a little bit.

[00:20:41.900] -Dr. Lemanne

Okay.

[00:20:42.320] - Dr. Gordon

And that's the study that was done in Korea a couple of years ago.

[00:20:45.200] -Dr. Lemanne

And these are formal cognitive tests, right?

[00:20:47.300] - Dr. Gordon

Yes.

[00:20:48.000] -Dr. Lemanne

Oh, yes. I feel better, but measurements but if.

[00:20:51.230] - Dr. Gordon

My 82 year old didn't test any better but she said I feel much better, I would keep her on it because I do it in what I consider as a very programmatic, safe way. And I'm always happy to expand that program. If you tell me there's some kind of cancer risk or something I'm missing. But that aside, somebody comes in, they want to take hormones I explain all the reasons I think it would be beneficial, but all the safety precautions we go through make sure their blood count, liver, kidneys, basically that they're all right. But they don't have breast cancer. So I like to have breast imaging and that somebody's checked their pelvis in the last year or two just to make sure there's not some giant fibroid there that they're going to have to deal with. Doesn't mean they can't take hormones, but they're going to have to deal with they have to agree with me that our protocol is that we're going to make the best guess of the dosing so that's an estrogen applied on the skin, generally through a patch which you can get at the local drug.

[00:21:43.150] -Dr. Lemanne

These are not pills.

[00:21:44.460] - Dr. Gordon

No. And that's very important because if you take pills of whatever kind of estrogen they run through the liver and they are metabolized to that e one estrogen that I told you about, that's the mischievous estrogen of menopause.

[00:22:00.190] -Dr. Lemanne

So if you take an estrogen pill, it goes into your stomach, it then goes into your small intestine and is absorbed there. And all of the blood from the small intestine goes straight to the liver. Is that correct? Anything in that small intestine then has to be processed by the liver. And that's a problem.

[00:22:19.120] - Dr. Gordon

If it's estradiol, if it's any estrogen, any estrogen, it will be metabolized to.

[00:22:25.010] -Dr. Lemanne

Estroge to the bad e one in the liver.

[00:22:28.180] - Dr. Gordon

Yeah, it's not terrible, but it's mischievous.

[00:22:30.490] -Dr. Lemanne

Put it that way. Okay. It's juvenile delinquent.

[00:22:33.270] - Dr. Gordon

Yeah. So phenyl delinquent. So when the big Women's Health International study was released in 2001, they were actually using oral synthetic estrogen that was largely estrone and an oral synthetic progesterone. And since then, a plethora of studies are around that show really the safe way to apply estrogen is on the skin. And that can be done through a compounded cream or a prescribed gel or a prescribed patch, which is great because you only have to change a patch one or two times a week.

[00:23:05.760] -Dr. Lemanne

And the dosing is specific.

[00:23:07.370] - Dr. Gordon

It is very specific. It will deliver so many milligrams of ester dial per 24 hours, period. And I do my best guess depending on body habitus, but that's only right two thirds of the time. So I say, I'm going to give you this prescription, and you're going to do the patch all the time, and you're going to cycle your progesterone and see how that goes for you, because that's what your body did when it was younger.

[00:23:29.150] -Dr. Lemanne

So that's only given part of the month. It's a month long process, and you're.

[00:23:34.710] - Dr. Gordon

Going to let me know when it either feels good or there's something that feels bad. And we're going to keep tweaking the dose might be over the first month or two until you feel good. Now I need to feel good. And what makes me feel good is that I know your levels are optimal, that your estrogen level is neither through the roof nor lower than the fat man in the waiting room. It has to be 50 picograms per milliliter or a little higher. And your progesterone number, completely different units, is five to 10% just by numerical comparison of the estrogen number. And that is thought to be protective against the endometrial cancer you get if you have estrogen by itself, I'm one step happy, my second step of happy. And this would be testing estrogen metabolism. So the liver metabolizes. First off, any estrogen you take by mouth, and it metabolizes it into a different estrogen, releases it back in the bloodstream. The liver also surveys the body and says, estradiol floating around. She's had a bourbon, a Scotch. I don't think you make those two drinks. Okay, scotch and water. And she's just driven by a toxic factory.

[00:24:46.530] - Dr. Gordon

I need to do some detoxing here. I'm going to put the estrogen through one pathway, the alcohol and the toxic environmental assault from another one and going to process them all out. But how the estrogen gets processed through the liver is detected in the urine, and there are metabolites of estrogen that are thought to be benign. 

00:25:18 testing metabolites in the urine using a DUTCH test. https://dutchtest.com/product/dutch-sex-hormone-metabolites/#:~:text=The%20DUTCH%20Sex%20Hormone%20Metabolites,MS%20for%20sex%20hormone%20metabolites! 

There are metabolites of estrogen that yield quinones and can wreak damage on DNA and are protected by glutathione and antioxidant. Is one the body can make, but you can also supplement. And then there's a pathway, which is the 16 hydroxy esterone pathway of metabolizing estrogen. There's the two. The four. The 16. Two is good, four yields genetic damage, and 16 is associated with the greater breast cancer risk.

[00:25:42.680] -Dr. Lemanne

So you're measuring these Moieties in the urine, and you can tell how the patient's body is responding to that particular hormone replacement program, and then you can make adjustments and get the urine harmonized.

[00:25:53.800] - Dr. Gordon

Yes, get the urine harmonized. It's kind of controversial whether it actually protects a woman from breast cancer to take down the breast cancer-associated component in the urine, and that's the 16. The 16. But you take it down with interventions that we know--and correct me if I'm wrong--reduce breast cancer risk. Diets high in cruciferous vegetables, broccoli, cabbage, cauliflower. Women from Poland who still eat cabbage four times a week have less breast cancer than women who move from Poland and stop eating cabbage four times a week. 

00:Foods included in a conventional Polish diet—cabbage and sauerkraut—are associated with a reduced risk of breast cancer in Polish migrant workers. https://pubmed.ncbi.nlm.nih.gov/34682540/ 

Okay, we address their estrogen metabolism and get it right. The blood levels have to be good for me, and once a year I ask them to repeat their breast imaging, and somebody can't come into me smoking, drinking, and eating only, and I'm not going to happily prescribe estrogen from them. That's just throwing something into a mix that I'm not very happy about. So I generally am working with patients who want to address the whole mix.

[00:26:55.310] -Dr. Lemanne

Who are health conscious and who are health conscious. Are there any bad side effects that you commonly see? And can you adjust the ratio of estrogen and progesterone replacement?

[00:27:04.690] - Dr. Gordon

There are minor effects, like breast tenderness, a little moodiness. So someone says, I don't mind if I weep at an occasional Hallmark commercial, but I don't want to weep because I see a puppy across the street. Okay, you're probably on an imbalance of hormones. So those are the minor side effects. The more significant ones that we monitor and have to tweak things for primarily consist of bleeding, not menstrual bleeding, but it seems like menstrual bleeding. It can be just because we've activated the uterus, and when we go through a hormone cycle, it bleeds. And the older a woman is, the more transient that bleeding will be will only go on maybe for the first few months that they're cycling. The younger the woman is, the more likely it's going to seem like it's a real period. But it can also come from abnormalities in the uterus. So if a woman has a fibroid, depending on where that fibroid is, it might just grow, which could be problematic. And then she's got lower abdominal heaviness, and we find an enlarged fibroid, or she could have bleeding from it if it's in the lining of the uterus.

[00:28:08.110] - Dr. Gordon

And the other source of bleeding can be something less welcome in the lining of the uterus. Hyperplasia, overgrowth of cells, confused overgrowth of cells metaplasia a polyp that's pretty easily removable. It's generated more by progesterone than estrogen. And then the one that we're most concerned about can yield an endometrial cancer. So, interestingly, if a woman has an endometrial cancer, it might take a long time for it to bleed if she's not taking estrogen. So she might sit around. Nobody knows. It's a pretty quiet organ if you're not taking hormones. And nobody ever knows until it's so big it's eating into a blood vessel and bleeding. If I give that woman estrogen because I don't look at her lining of her uterus before I start, she'll start bleeding right away, and it won't respond to Tweaks in the hormone dose, and you'll have an earlier diagnosis.

[00:29:11.240] -Dr. Lemanne

So that might be a benefit to that patient.

[00:29:13.450] - Dr. Gordon

Yes, it is a benefit. It doesn't feel good because you just investigated my bleeding and told me I have cancer. But the estrogen does make a cancer bleed earlier.

[00:29:23.710] -Dr. Lemanne

It's ideal, it sounds like, to begin the process of hormone replacement around perimenopause. But do you ever recommend that an older woman who has not had any hormone replacement therapy, say, in her 70s, begin hormone replacement therapy?

[00:29:39.070] - Dr. Gordon

I do for two reasons. Would I recommend hormone replacement therapy later in life? I'd say three. If some woman has a friend who just feels great and is convinced that she's going to live longer with estrogen, I'd say you're a little bit outside the window that it's generally thought to confer longevity protection.

[00:29:56.020] -Dr. Lemanne

But what is that window?

[00:29:57.990] - Dr. Gordon

We don't really know about that. So here are the three reasons to do it in an older woman. Brain health, cardiovascular health, and general longevity. No bones. Four. We'll do four there. Right. The ones that I would do without hesitation, a 72 year old woman comes in to see me and she's having some cognitive trouble, or she's having osteoporosis and doesn't want to go on the conventional medications for it. Absolutely. Hormone replacement therapy could be of benefit to a woman in both those situations. The other one is that she's heard from her friends that they feel better on hormones and wants to try it. As long as she can do it safely and doesn't have any contraindications, I'll do it with her. And the fourth. One where there really is still considered to be this window is cardiovascular health. So it was thought for a long time that to get any benefit in any region of the body or well-being, a woman has to start hormones within the first couple of years of cessation of her periods. That's really been discredited by: I help women build bones in their would say. My clinical experience has confirmed for me that it can work in that area.

[00:31:11.000] - Dr. Gordon

There's research out of Korea working with women up into their 80s showing less cognitive decline with age in women who are using hormone replacement therapy. 

00:

Referring to that Korean study again.. https://journals.lww.com/menopausejournal/Abstract/2018/08000/Menopausal_hormone_therapy_and_mild_cognitive.5.aspx  

So there's a benefit quite late in life. But where that area is far more gray is cardiovascular health. And in general, if you're growing up under some genetic fear or you notice that you have high blood pressure, you have other risks, and you want to take hormone replacement therapy for cardiovascular health, it's not clear that starting it in your 60s is going to give you any benefit. That's the woman who really should be alert to this in her perimenopause years and early menopause and get it started before her cardiovascular system suffers permanent damage from loss of estrogen.

[00:32:00.810] -Dr. Lemanne

Well, what a fascinating topic. I think the takeaway is that for brain health, estrogen and progesterone replacement therapy should very much be considered. And the earlier the better for many people. Although it's never too late.

[00:32:12.390] - Dr. Gordon

It's never too late. And I just want to add one little pearl because of course there's some women who either for cost or other reasons don't want to take hormone replacement therapy. And this is what I learned from my genetic consultation with IntellxxDNA is that the supplement genestein, which is a derivative of soy, which I used ages ago in breast cancer patients who had osteoporosis, has long been known that it activates estrogen receptors in the bone genestein and it also activates estrogen receptors in the brain. 

00:33:13   Genistein can confer protection against bone and cartilage  diseases.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9492956/ and is emerging as a therapeutic option against the pathogenesis of memory impairment.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8746870/

So a woman who didn't want to take hormone replacement therapy but wanted these benefits, could take genestine in the doses somewhere between 50 and 150 milligrams a day.

[00:32:59.240] -Dr. Lemanne

That's not very much. So you generally have to take a supplement.

[00:33:01.860] - Dr. Gordon

You generally take a supplement. And the one that I know pretty well is 125 milligrams. But you're not going to have somebody sloppy making a supplement out of genestine.

[00:33:12.310] -Dr. Lemanne

What do you mean?

[00:33:12.990] - Dr. Gordon

So I'm pretty particular about the brand of supplement I want. And there's some brands that I'll buy something from them that's easy zinc, gluconate. But I won't buy something complicated from them like melatonin.

[00:33:26.390] -Dr. Lemanne

So you vet this supplement brand that you recommend for your patients.

[00:33:30.030] - Dr. Gordon

I do too. So one in five women in the United States is at risk for getting Alzheimer's disease. And at women my age, it's like one in three or four.

[00:33:40.060] -Dr. Lemanne

Wow.

[00:33:40.460] - Dr. Gordon

And by the time you reach 80 or 85, it's one half of women at risk for getting Alzheimer's disease. Women are much more afraid of breast cancer than anything else. But what are the lifetime risks?

[00:33:51.920] -Dr. Lemanne

Sure, yeah. The lifetime risk of breast cancer is one in eight, which is much lower than Alzheimer's. And a very esteemed colleague of yours in the antiaging and hormone replacement professional world called me up the other day and said, why are you oncologists not taking that into consideration? A woman is more likely to die of dementia than she is of breast cancer. And she's absolutely right. And so, yes, that has to be put in the mix. When you're dealing with patients who are at risk for several different disorders, what is really facing them at this moment, and the biggest problem that they might develop.

[00:34:26.150] - Dr. Gordon

Right. And of course heart disease goes in that mix. But another question about breast cancer, I would imagine in my mid seventy s that my breast cancer risk has actually gone down a little bit.

[00:34:36.150] -Dr. Lemanne

You know, you're aging out of the the highest risk group. Right.

[00:34:38.970] - Dr. Gordon

So I am at much greater risk for Alzheimer's than breast cancer.

[00:34:42.400] -Dr. Lemanne

Absolutely. Yes, indeed.

[00:34:43.790] - Dr. Gordon

Okay, I better go take some hormones, right?

[00:34:47.790] -Dr. Lemanne

Maybe eat some tofu.

[00:34:51.230] - Dr. Gordon

You have been listening to the Leman Gordon Podcast where docs talk shop.

[00:34:56.960] -Dr. Lemanne

For podcast, transcripts, episode notes and links, and more, please visit the podcast website@dockstockshop.com. Happy Eavesdropping. Everything presented in this podcast is for educational and informational purposes only and should not be construed as medical advice. No doctor patient relationship is established or implied. If you have a health or a medical concern, see a qualified professional promptly.

[00:35:33.280] - Dr. Gordon

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[00:35:45.310] -Dr. Lemanne

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[00:35:59.870] - Dr. Gordon

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[00:36:06.680] -Dr. Lemanne

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