[00:00:00.100] - Dr. Gordon

estrogen never caused breast cancer to begin with.

[00:00:03.240] - Debra Zaslow

I'm taking the testosterone again and this is what's happening. My libido was up. I was definitely more interested in sex, but who'd want to fuck me because I was such a bitch?

[00:00:16.970] - Dr. Gordon

Men walk around with levels of estrogen higher than postmenopausal women do.

[00:00:23.850] - Dr. Lemanne

You have found your way to the Lemannene-Gordon podcast, where docs talk shop. Happy eavesdropping! I'm Dr. Dawn Leman. I treat cancer patients.

[00:00:42.700] - Dr. Gordon

I'm Dr. Deborah Gordon. I work with aging patients.

[00:00:46.400] - Dr. Lemanne

We've been in practice a long time.

[00:00:48.790] - Dr. Gordon

A very long time.

[00:00:50.410] - Dr. Lemanne

We learn so much talking to each other.

[00:00:52.420] - Dr. Gordon

We do. What if we let people listen in?

[00:00:59.710] - Dr. Lemanne

In this episode, Dr. Gordon and I cover hormones again because you, our listeners, have let us know that that topic is one you care a lot about because many of you rely on hormone replacement therapy to maintain vitality and libido, as well as cognitive and metabolic health. And we are joined today by a special guest, well-known author and storyteller, Debra Zaslow, who generously shares with us her personal experience of hormone replacement therapy, including effects on mood and libido. What emerges from this conversation is not a simple for or against, but a much more nuanced picture, one that challenges longstanding assumptions, including the idea that hormones are uniformly dangerous, especially after cancer therapy, or that they can be prescribed without careful measurement and adjustment. We talk about how different formulations and delivery methods can have dramatically different effects, why dosing matters far more than most people realize, and how quickly things can go right or wrong. Deborah's story brings this into sharp focus. Her experience is relatable, sometimes surprising, and at moments disarmingly candid, but always in service of helping others understand what these therapies can actually feel like in real life, beyond the textbook or the prescription pad.

[00:02:29.500] - Dr. Lemanne

If you've ever wondered whether hormone therapy is helping you, harming you, or simply not doing anything, this episode will give you a more precise way to think about it. Today we have, we have another Debra in the studio with us. Yeah, we have Debra Zaslow, previously known as Debra Gordon Zaslow. So it's kind of confusing, but we'll call you Debra Zaslow today.

[00:02:58.710] - Debra Zaslow

For purposes of identification.

[00:03:01.040] - Dr. Lemanne

And Debra Zaslow is a friend of all of ours. And we're happy to have her today. And she is our audience. Thank you for coming.

[00:03:10.040] - Debra Zaslow

Glad to be here.

[00:03:11.480] - Dr. Lemanne

We hear you have something to say about Testosterone?

[00:03:15.510] - Debra Zaslow

Would you want me to talk about that?

[00:03:17.340] - Dr. Lemanne

Yes, but not yet.

[00:03:18.870] - Dr. Gordon

Hold that thought. Keep me in check.

[00:03:24.410] - Dr. Lemanne

So Deborah Gordon, you told me last night about an article. I told you I wanted to talk about hormones and you said, "Oh, well, did you see this new JAMA article?" And so this morning, you know, 5 minutes before our recording session, I had to run and look it up. And thank you so much.

[00:03:40.380] - Dr. Gordon

Isn't that an interesting article?

[00:03:41.840] - Dr. Lemanne

Oh yes, and it's about time, huh? Mm-hmm. Yeah. And what it is for our audience is the JAMA has reported that the FDA has removed the black box warning about hormone replacement therapy. And so we're gonna talk about hormone replacement therapy. I'm gonna talk about hormone replacement therapy in the setting of previous diagnosis of breast cancer, which I think every woman who's been diagnosed with breast cancer has been told, "You can never ever take hormones again." And now that this is changing a bit, I think it'll be of interest to pretty much everyone who might take hormones, which is men and women. Men and women.

[00:04:29.430] - Dr. Gordon

And I think, you know, the article that I'm talking about today wasn't the Black Box article, but it does—

[00:04:35.840] - Dr. Lemanne

Oh, I looked at the wrong article?

[00:04:37.600] - Dr. Gordon

Yeah, but that's a good one.

[00:04:39.450] - Dr. Lemanne

You know, I'm not prepared. Okay, we're gonna go home. I'm gonna go get more prepared for this.

[00:04:43.370] - Dr. Gordon

No, but it was pertinent to exactly what you said, and the thing is, when it comes to breast cancer and hormone replacement therapy, the first item on the agenda has to be getting rid of that black box warning because estrogen never caused breast cancer to begin with. But there are so many different settings. So, so many people said to me, "Why are you on hormones? Your mother had breast cancer." I said, "Oh, that's not entirely true. She died of it, and her mother had it too." So I have a I have a really strong family history. That's why I'm on hormones. But the article in JAMA yesterday was hormone therapy after oophorectomy. And so, you know, people who have the BRCA gene variant, which I do not, even though I have a strong family history, they have always been advised to have their ovaries removed, get rid of estrogen, and not take hormone replacement.

[00:05:35.750] - Dr. Lemanne

That's right. And that has been changing gradually. Over the past 10 years. And so that's something really interesting, and we should talk about that. I have a few things to say about that, and I, you know, one of them being that people with, you know, on the West Coast we say BRCA, and on the East Coast they say BRCA.

[00:05:58.620] - Dr. Gordon

I say BRCA, so I don't know, what am I doing here?

[00:06:02.240] - Dr. Lemanne

I don't know, you better move to the East Coast. Yeah, so I say BRCA, and BRCA1 mutation carriers. Everyone has a BRCA gene, all right? But some people have a broken BRCA gene, and those are the people we say have BRCA1, BRCA2. It's a mutation in one of those genes. And those genes have a lot of functions, but one of the main functions is to repair DNA when it's damaged. So if you have a DNA accident at your dental X-ray, or if you are hit by the wrong cosmic ray, or something like that, you can have a damage in your DNA, and if that happens in one of the breast cells, it can, doesn't always, if it's not repaired, lead to cancer. So people with a mutation in the repair genes, like BRCA1 or 2, don't repair those types of damage very well. And so that increases the risk of breast cancer in those patients. But BRCA1, mutation carriers actually usually have what's called triple negative breast cancer. Their breast cancer is not related to hormones. So triple negative means that you have neither estrogen receptor positivity in your breast cancer, progesterone receptor positivity, you don't have that either, and you don't have a third target of treatment called HER2 amplification.

[00:07:24.450] - Dr. Lemanne

So those are really technical aspects of breast cancer diagnosis and treatment, but that's the meaning of it for those of us who've, you know, who deal with that. But for the average person, if you don't have a breast cancer that's related to hormones, do you really have to avoid all hormone therapy afterwards? And BRCA1 and 2 mutation carriers often are at increased risk or are at increased risk of fallopian tube cancer. We used to call it ovarian cancer, but it turns out that these cancers probably typically start in the fallopian tubes, which is the little bridge between the ovary and the uterus. And so they've been advised to have those organs removed, the ovaries and the fallopian tubes, and usually the uterus at the same time, but at least the ovary and fallopian tube, to decrease their risk of cancer. And therefore, if they have no ovaries and they're premenopausal, what are they to do in terms of, you know, hormones?

[00:08:22.100] - Dr. Gordon

I would say even if they're postmenopausal, which opens a whole nother can of worms.

[00:08:27.090] - Debra Zaslow

Right, yes.

[00:08:27.250] - Dr. Lemanne

And we should talk about that too.

[00:08:28.360] - Dr. Gordon

Me too. Yeah. But the study, and I actually do have somebody who had that surgery premenopausally and now I've finally talked her into going on hormones. But what this study shows, just came out yesterday, was that using estrogen-only replacement therapy, which is all you need really if you don't have a uterus, reduces the risk of breast cancer in BRCA1 women.

[00:08:52.950] - Dr. Lemanne

That's fantastic. Well, you know, estrogen has been exonerated in breast cancer. Estrogen does—

[00:08:59.940] - Dr. Gordon

About time.

[00:09:01.100] - Dr. Lemanne

In all comers seem to decrease the risk of breast cancer. So why is there this connection? Do you wanna talk a little bit about, you know, progestins, progesterone, and estrogen in the etiology of breast cancer?

[00:09:17.510] - Dr. Gordon

I have to do this with a little bit of a somber note because in July of 2002, headlines came out that yielded a massive traumatic brain injury to the most of OB-GYN science that started in 2002 and has prevented them from learning new information, leading all the way up to about the last 2 or 3 years when they're finally— their TBI is partially recovering. But in 2002—

[00:09:52.610] - Dr. Lemanne

I just have to say, Farah, she's She's joking.

[00:09:55.870] - Dr. Gordon

No, but I'm not. Oh, oh, okay. But if you were a prescriber or a woman on hormones, you know where you were in July 2002 when they said, "Women's Health Initiative trial stopped because estrogen causes breast cancer." And most women stopped their hormones. Most doctors stopped prescribing it. And over the next, really half year, but certainly over the next 5 to 10 years, they began qualifying that headline with, "Oh, it wasn't the estrogen, it was the progesterone. Oh wait, we're sorry, it wasn't real progesterone that caused breast cancer. We were using a synthetic one that doesn't work the same way as a natural one." Wait a minute, Dr.

[00:10:43.440] - Dr. Lemanne

Gordon, do you mean that there are subsets? Of patients that we ought to treat differently from the average patient?

[00:10:54.280] - Dr. Gordon

You mean, there's this concept of individualizing medical treatment that I think it's your bread and butter, Dr. Lemanne.

[00:11:03.620] - Dr. Lemanne

Oh, okay. I don't eat bread, but you know—

[00:11:06.700] - Debra Zaslow

Sometimes she does at my house.

[00:11:09.190] - Dr. Lemanne

I'm being polite, Deborah Zaslow. Yeah, yeah. But it's good.

[00:11:13.490] - Dr. Gordon

But it not only has to be individualized, is that there really has been a wealth of information about the different effects of estrogen therapy. And in this case, nobody's using horse urine estrogen anymore.

[00:11:28.640] - Dr. Lemanne

Well, no, go back and tell us about Premarin.

[00:11:32.980] - Dr. Gordon

Right, so—

[00:11:33.630] - Dr. Lemanne

Which stands for Pregnant Mare Urine. Yum.

[00:11:38.270] - Dr. Gordon

Yum. We have been knowingly going through menopause for about 2,000 years, but only—

[00:11:47.700] - Dr. Lemanne

Well, speak for yourself.

[00:11:49.090] - Dr. Gordon

Yeah. As a species, one of the 5 species that goes through menopause.

[00:11:54.800] - Dr. Lemanne

There are 5?

[00:11:57.500] - Dr. Gordon

Before we go on, may I ask you a quick favor? Hit the subscribe button. Your hitting that subscribe button really, really matters. You're making sure cutting-edge ideas that matter to you move to the center of medical discourse where they belong. Thank you. There are only 5 animal species that go through menopause.

[00:12:19.490] - Dr. Lemanne

Are they all primates?

[00:12:20.920] - Dr. Gordon

You would guess that, wouldn't you?

[00:12:23.020] - Dr. Lemanne

Well, I'm, I'm, yeah, okay, I'll guess that.

[00:12:25.670] - Dr. Gordon

Not one.

[00:12:27.420] - Dr. Lemanne

We're primates.

[00:12:28.540] - Dr. Gordon

Not one other one.

[00:12:30.150] - Dr. Lemanne

Oh.

[00:12:30.710] - Dr. Gordon

All the others are toothed Whales.

[00:12:34.000] - Dr. Lemanne

Okay. Not something on my radar, but okay.

[00:12:36.740] - Debra Zaslow

They're mammals.

[00:12:37.680] - Dr. Lemanne

They're mammals.

[00:12:38.180] - Dr. Gordon

Yes. Yes. So, but every other animal on the planet is fertile until the day they die. And we thought we were—

[00:12:48.830] - Dr. Lemanne

Including male humans.

[00:12:50.590] - Dr. Gordon

Yes.

[00:12:51.230] - Dr. Lemanne

Okay.

[00:12:51.950] - Dr. Gordon

And we thought we were until about 2,000 years ago when some of us began living long enough to live past menopause, which at that point happened at about age 40. And now it happens at about age 50. And only in the last really 100 years have we started living 10, 20, now even 30 years past menopause. And so it only became medicalized in the middle of the 1900s. And the first pharmaceutical achievement was just what you described, Premarin, pregnant mare's urine, which could be, you know, patented and sold by drug companies. But if you— and that's what was the original treatment for menopause. And it worked really great Great, except for the about 10% of women who got uterine cancer. They discovered from that that, oh, if they actually give them something that's like the progesterone that their body makes, that will protect them from uterine cancer. But gee, we have to be able to patent it. So they came up with a synthetic progesterone called Provera, which shares with regular progesterone one feature, which is protecting the uterus, and in every other way is diametrically opposite to conventional, to bioidentical progesterone. The mood effects are different.

[00:14:16.400] - Dr. Gordon

The effects on the breast tissue are different. Everything is different except they both protect the uterus.

[00:14:21.960] - Debra Zaslow

So—

[00:14:22.180] - Dr. Lemanne

And those are called, for our audience, those are called progestins, what Dr. Gordon is talking about here, as opposed to progesterone, You know, different words.

[00:14:32.750] - Dr. Gordon

Yes. And progesterone is in the broad category of progestins. So if you want to be, you know, it is something that acts in a progestin, estrogen blocking in the uterus sort of way. But it's, it's not a pharmaceutical progestin. It's a bioidentical progesterone. When you take bioidentical hormones, you can do a blood test some point later and think that somebody is making their own estrogen and progesterone. Whereas if they take Premarin and Provera, they never get the same estrogen in their blood and they don't get anything that looks like progesterone.

[00:15:15.310] - Dr. Lemanne

Let me, let me ask you something here, Dr. Gordon. Are bioidentical hormones patentable?

[00:15:25.200] - Dr. Gordon

Not in the same way. So in this case, it's by delivery system.

[00:15:30.410] - Dr. Lemanne

So people have figured out how to make some money by changing the delivery system?

[00:15:34.840] - Dr. Gordon

Mm-hmm.

[00:15:35.470] - Dr. Lemanne

Or by patenting the delivery system. So what kinds of delivery systems are used for these drugs? Are they not just pills?

[00:15:42.620] - Dr. Gordon

So for estrogen, it comes in pills and creams and gels, and my favorite being patches. And currently there is a global shortage of estrogen patches. I cannot, and there's only really one brand that's very, very reliable. And people, I'm having, people are chasing all over literally the world trying to find a source for the patches because they used to be so easy to find and now they're so hard. So those are the delivery systems for estrogen and progesterone. The pharmaceutical option is really always just capsules. And these are very multipurpose capsules. They can be taken in your mouth, your vagina, or your rectum. And they all— all routes lead to the same uterine benefit.

[00:16:41.780] - Dr. Lemanne

And because all of the routes lead to the bloodstream, I think people, you know, want to know that anything you put on your skin or on your mucous membranes, whether it's your mouth or other places, will get into the bloodstream.

[00:16:57.830] - Dr. Gordon

The caveat here, and this goes for oral progesterone and oral estrogen, they first go to the liver before they go to the bloodstream.

[00:17:09.230] - Dr. Lemanne

And what's that? What's the problem with that?

[00:17:11.290] - Dr. Gordon

The liver has its way with them and it alters them. It's estrogen, so estrogen in the body comes in 3 forms and you're taking a pill that says, Oh, estradiol. This is the lab level that Deborah's gonna check when we do labs last time. They swallow their estradiol pill, it goes to the liver, and it comes out as estrone, which is more carcinogenic than estradiol and harder on the brain.

[00:17:41.870] - Dr. Lemanne

So taking estradiol by mouth is more carcinogenic than putting it on your skin in a patch or a cream?

[00:17:47.390] - Dr. Gordon

Yes.

[00:17:47.710] - Dr. Lemanne

Or in the vagina or in the rectum?

[00:17:49.700] - Dr. Gordon

Yes.

[00:17:50.260] - Dr. Lemanne

Okay.

[00:17:50.660] - Dr. Gordon

Because you go put it in the vagina or the rectum and it really does just seep slightly more slowly, but sleep seeps into the blood vessels that pass by the, you know, that run through those mucous membranes. And similarly with progesterone, if you take it by mouth, everybody loves progesterone who takes it because they sleep so well, but they're only sleeping so well because of what the liver does to progesterone. So it turns estradiol into another human hormone estrogen, it turns progesterone into allopregnanolone.

[00:18:27.450] - Dr. Lemanne

This is getting pretty complicated, Dr.

[00:18:30.020] - Debra Zaslow

I have some questions if, if you want audience questions.

[00:18:33.880] - Dr. Lemanne

Yes, go ahead, audience. Okay.

[00:18:37.150] - Debra Zaslow

And a female. How apropos for today. I have been taking a rub-in cream of bioidentical estrogen and progesterone. For many years, prescribed by the gynecologist who recently retired, who had lots of wonderful ideas and things, and she wanted to make sure it was bioidentical. But we recently— and I'm going to— about a year ago, tested some hormone levels. We were looking particularly because I was having a lot of headaches, and we were looking at You know, where the levels were. Well, it turned out, at least on this test, which I understand is unreliable, that my levels were well below a postmenopausal woman, even though I've been rubbing in this estrogen and progesterone cream for years.

[00:19:32.550] - Dr. Gordon

There's no other hormone in medical practice that a doctor would give to you and not check the levels and make sure and have a goal in mind. I mean, I'm sorry, I'm breaking you off, but—

[00:19:44.910] - Dr. Lemanne

You sound really— You're passionate about this, Dr. Gordon.

[00:19:48.570] - Dr. Gordon

How did you pick that up? Can you imagine giving cortisol, giving thyroid, giving insulin, and not checking its physiological effect?

[00:20:00.120] - Debra Zaslow

Well, we did check.

[00:20:01.570] - Dr. Gordon

But years later, you're saying?

[00:20:03.260] - Debra Zaslow

Yes, I wasn't having regular tests, but I have had a few, but over the years, but not many. But one of the things then that we discovered later was that my estrone level was too high.

[00:20:17.050] - Dr. Gordon

Exactly.

[00:20:18.350] - Debra Zaslow

Exactly. Okay. So she actually started taking indole-3-carbinol in order to— I think that was what that was for. Do you know what I'm talking about?

[00:20:26.670] - Dr. Lemanne

I do.

[00:20:27.390] - Dr. Gordon

And that doesn't so much alter that. I would do a little something different, but I want to make a— just, okay, I have to, you know, I'm a little bit of a wiseass with not a very good sense of humor. But the level you got in your most recent blood test that you said was a year or A couple years ago. Which was not much higher than somebody who'd not been on hormones. I would tell you also, men walk around with levels of estrogen higher than postmenopausal women do.

[00:20:58.830] - Debra Zaslow

Is that why they get breasts?

[00:21:00.580] - Dr. Gordon

Oh, it's why they have bones and don't get as much Alzheimer's as women do.

[00:21:05.080] - Debra Zaslow

Ah-ha.

[00:21:06.280] - Dr. Gordon

That men— think about how much estrogen is really crucial for the bones, and you have to have some combination of estrogen and testosterone, and men get bone both of them. And men's hormones don't fall off a cliff at a certain age. Dr. Lemanne was just saying, you know, men can be fertile up until the day that, you know, they're 100 years old. You know, their hormones don't fall off a cliff, but women's really do. And we outlive our fertility so that we can be— the other Deborah and I shared pictures today— we can be happy grandmothers and help. You know, we are the species, we and the four-toothed whales that go through menopause, We live in some degree of extended family units. It's helpful that we're not trying to get pregnant by our daughters' male partners. It's helpful that we can— I mean, that's what dogs and cats would do. We can be helpful to the bringing up of the next generation. But women suffer from health reason— in health ways, brains, bones, cardiovascular disease, by completely losing their hormones to lower than the level of their husbands in menopause. Anyway, I totally interrupted you and diverted you from— I think you were going somewhere beyond where I interrupted you, Deborah.

[00:22:30.720] - Debra Zaslow

No, no, this is all very, very interesting, and I'm going to make an appointment with you later.

[00:22:37.290] - Dr. Lemanne

So, well, I have— to talk about hormones. So let me see if I can package this up and tell you what I've gotten from the last few minutes of our conversation. Hormones and hormone replacement is really important, and for women. And what I understand from my own reading and statistics is that women live longer than men, but they have poor health. Their health is worse. They have a poorer healthspan. So they spend more of their old age in decline and poor health and not active, even though men die sooner. And so it sounds as though hormone replacement therapy, if done carefully and with careful measurements so that the hormone levels can be adjusted based on the method of delivery— is going through the liver or through the skin, those kinds of things— those have to be attended to. And it sounds like that's coming into play. It sounds like, Deborah Zaslow, like your doctor just before they retired was starting to do that and get into measurements. And Deborah Gordon, Dr. Gordon, it sounds like you're doing that very judiciously and are recommending that that be done. And so estrogen, there are several different ways of giving that, different ways of methods of giving it to people.

[00:23:58.290] - Dr. Lemanne

Progesterone can only be given by mouth. There are several different types though, and you want to make sure you get the bioidentical one.

[00:24:04.130] - Dr. Gordon

But it can, that same oral can be put in other body orifices.

[00:24:07.750] - Dr. Lemanne

Okay, thank you. And then there's a third hormone, testosterone.

[00:24:11.420] - Dr. Gordon

Ta-da!

[00:24:12.320] - Dr. Lemanne

That we, you know, that people associate only with men in many cases. But do you, I know Debra Zaslow has something to say about that. And Dr. Gordon, I think you do too.

[00:24:24.760] - Debra Zaslow

Mm-hmm. Do you want me to talk about what happened when I tried testosterone and get your opinion?

[00:24:30.930] - Dr. Lemanne

Oh, we do, yeah.

[00:24:32.010] - Debra Zaslow

Yes. Okay. A different— this was because at a certain age, and it seems like it was about 10 years ago, you know, when I was in my 60s, so I was lamenting my dip in libido. So I wanted to do something to get my frisky nature back. So this doctor friend had a rub-in cream, and Deborah Gordon knows about this, and she recommended that I try it. And unfortunately, she gave me the wrong— there's two kinds, and one has a higher dose. She gave me the higher dose. What happened was that— and I've been married for many years, and my husband and I get along very well after 40-some years of marriage. If we bicker about something, we just laugh because it's There's nothing to fight about. But all of a sudden, we were fighting. We were bickering. And he answered me something, and I just started screaming at him and crying and every emotion that could be. I mean, I was just raging out of control. And all of a sudden—

[00:25:45.780] - Dr. Lemanne

And this was when you were taking testosterone? Yeah.

[00:25:48.510] - Debra Zaslow

A couple days after.

[00:25:50.530] - Dr. Lemanne

Oh, right away?

[00:25:51.330] - Debra Zaslow

Yeah, 2 or 3. I don't remember, but it was a few days after. And all of a sudden, I stopped and I said, This is the testosterone talking. It's not me. And therefore, we— I just stopped taking it for a few weeks. And then this Dr. Friend recommended that I do the lower dose, like twice a week or something, instead of daily. So I waited a few weeks to do that. And then I did it. And again, we were starting to bicker. And I said, you know what? I'm taking the testosterone again and this is what's happening. My libido was up. I was definitely more interested in sex, but who'd wanna fuck me? Because I was such a bitch.

[00:26:39.890] - Dr. Gordon

I think the only reasons to use testosterone is if you want more brain cells, muscle cells, bone cells, libido, enjoyment in sex.

[00:26:47.920] - Dr. Lemanne

Well, who wouldn't?

[00:26:48.960] - Dr. Gordon

Who wouldn't want all those things? Dawn, you'll know that that sounds a lot like my rationale for why everybody should take creatine, and they do work a lot in similar ways in enhancing muscle health and integrity. But when I give people testosterone, I don't mix it with other creams. I always want them to titrate the testosterone for themselves, and I give them my best dose of what— best guess of what a dose would be for them, but I always give it to them with a range that you can do And when it comes from the compounding pharmacy, it's one click or two clicks, or I would say to someone who's got it in a syringe, a quarter gram or half a gram daily for a little bit and then less often. And I tell them, I eventually have a goal for you of, that's physiological and metabolic, but it's highly dose dependent and it, And anyway, it's just really highly dose-dependent and there's different places you can— and it is topical. And there's, you know, with any prescription that, gee, this might be a lifelong prescription, there's always going to be tweaks. And yours came on very quickly.

[00:28:04.630] - Dr. Gordon

But, you know, you also, it sounds like you probably had insufficient estrogen and progesterone and perhaps pregnenolone. Which is a hormone we only really learned about in medical school, and then I picked up again when I did cognitive health. Dawn, in your medical practice, do you spend much time thinking about the hormone pregnenolone?

[00:28:25.310] - Dr. Lemanne

I don't, except when I get patients from you who are on pregnenolone or who ask about pregnenolone. Why don't you tell us a little bit about it? And, you know, I understand that it's a precursor to the steroid cascade.

[00:28:41.190] - Dr. Gordon

Yeah, it's the mother of all hormones. So in a little talk I just made recently about hormones, not only did I get to put in slides with killer whales on them, but I put in a slide of a mama cat with a whole bunch of little kittens.

[00:28:53.770] - Dr. Lemanne

Where can we see this talk? Is it on YouTube?

[00:28:56.190] - Dr. Gordon

No, it's going to be on an online conference that we will link to in the notes.

[00:29:01.800] - Dr. Lemanne

Okay.

[00:29:02.190] - Dr. Gordon

That's probably gonna happen before we get this posted. It happens at the end of the month. It's an Alzheimer's prevention summit. But pregnenolone not only is the precursor to making all these other hormones. It's depleted in times of stress. It's the first hormone your body makes from cholesterol. Very, very important, not only because it's a precursor to all these other hormones, but because it really is a neurohormone. It's what enhances, maintains, rebuilds the myelin sheath, the protective coating that enables neurons to sit close to each other.

[00:29:38.550] - Dr. Lemanne

Wait a minute. Wait a minute. Did I hear you say that all of these wonderful hormones are made from cholesterol?

[00:29:47.880] - Dr. Gordon

Yeah. Yes. Yes.

[00:29:52.240] - Dr. Lemanne

So we won't go too far off of this track. I'm going to bring you right back to this track, but I want our audience to notice that. And if you want to hear about all the good things that cholesterol does, Let us know and we'll have a podcast episode about that.

[00:30:08.840] - Dr. Gordon

Mm-hmm, particularly brain cholesterol. And I have something new to say about that.

[00:30:13.390] - Dr. Lemanne

And perhaps lowering the cholesterol in everyone over 65 might not be such a great idea. Yeah, okay, go ahead. I'm sorry. So you were talking about pregnenolone.

[00:30:24.930] - Dr. Gordon

Pregnenolone does this mechanical work of enabling the neurons in the brain to crossfire without setting each other off. You know, you're sending messages down one neuron literally hundreds and thousands of neurons at the same time, and you don't want your eye to start twitching because you're scratching your foot.

[00:30:44.310] - Dr. Lemanne

Who is that? Why that happens?

[00:30:45.970] - Dr. Gordon

Yeah, your neurons are crossing, but it helps regulate cortisol, and it's the ah hormone, you know, it really— if you've gone through stress, it's depleted. When I first started doing this brain work, You know, I hadn't looked at pregnenolone since we learned about the pregnenolone steal, which is a cortisol event decades ago. And so I had to refresh my memory, but it's a newer awareness because it's a really wonderful brain-soothing hormone that enhances better quality and length of deep sleep and REM sleep. To make it all, you know, copacetic. Pregnenolone, we should all, everybody should be tested for and normalize their pregnenolone, and it's a supplement.

[00:31:40.510] - Dr. Lemanne

What is, you have talked about this, Dr. Gordon, in the past, and forgive me, I need to come and see you for some hormone therapy. What is, tell us again, the pregnenolone steal, and what does it have to do with cortisol?

[00:31:56.930] - Dr. Gordon

I don't think I could do it justice.

[00:31:59.750] - Dr. Lemanne

Well, one goes up and the other goes down. I mean, I'm guessing that, okay, being a good test taker, I got through med school. So, you know, it's question C, or answer C. But, so when the pregnenolone goes up, the cholesterol goes down?

[00:32:14.970] - Dr. Gordon

No, when the cortisol goes up, the pregnenolone goes down.

[00:32:18.610] - Dr. Lemanne

Isn't that the same thing?

[00:32:19.780] - Dr. Gordon

You said cholesterol.

[00:32:20.980] - Dr. Lemanne

Oh, I'm fixated on cholesterol these days, so forgive me, you're right. Pregnenolone goes down. Goes up, cortisol goes down.

[00:32:31.080] - Dr. Gordon

And the other way around. When cortisol goes up, it's— you lose pregnenolone. So you want to have an optimal level of both. And, you know, you don't really take cortisol as a supplement kind of thing. You can take cortisol precursors, and those would be both pregnenolone and DHEA, which is also a testosterone. Hormones are fascinating. I love hormones.

[00:32:56.750] - Dr. Lemanne

And, you know, pregnenolone and DHEA over-the-counter.

[00:33:00.100] - Dr. Gordon

Yes, yes, they are.

[00:33:01.780] - Dr. Lemanne

Do you wanna talk a little bit about quality?

[00:33:04.910] - Dr. Gordon

You know, your favorite, so I, in general.

[00:33:08.930] - Dr. Lemanne

For people who in the audience who are, you know, already exploring these things, don't do this without your doctor's hand in yours.

[00:33:16.930] - Dr. Gordon

So it'd be great to get your levels tested 'cause you already might have great levels of them. And you could just say roughly around 100 is a good level for DHEA and pregnenolone.

[00:33:29.210] - Dr. Lemanne

Wait, is this the blood level or the?

[00:33:31.200] - Dr. Gordon

Blood level.

[00:33:32.460] - Dr. Lemanne

Okay, and what kind of doses do these over-the-counter supplements come in?

[00:33:37.240] - Dr. Gordon

Somewhere between— they come in 10, 25, 50, even higher milligrams than that. And that's when you go, "Oh my goodness, I tested my pregnenolone. It was immeasurably low. Start with 25 milligrams, see if it brings it up. Not very much. Well, then take 3 of them or look for a bigger pill." But are you saying—

[00:33:58.560] - Dr. Lemanne

I'm I'm gonna push on this because I think this is really important. Are you saying then if you take pregnenolone, your body will distribute the pregnenolone into the various pathways that are needed, decreasing cortisol or increasing it if needed, decreasing or increasing estrogen, DHEA, testosterone, progesterone?

[00:34:17.610] - Dr. Gordon

I don't think anyone can say that there's validated research, but I'd say all of us who work with these hormones, so all the brain doctors, we have the clinical experience that suggests that is true. So I have somebody whose pregnenolone I've just recently been replacing and bringing up to a more acceptable range, and her cortisol has gone from too high down to a more normal level. And I don't know if— I don't know that the pregnenolone— it didn't help her make cortisol, but it prevented her stress level that was generating the high cortisol. So it's complicated because there's a biochemistry interaction between the two, and then there's an experiential interaction between all these hormones.

[00:35:03.330] - Dr. Lemanne

Let me ask another question. And this is for both, both of you, both our guest and Dr. Gordon. So to our guest, Deborah Zaslow, you felt these effects of these hormones after just 3 days.

[00:35:18.110] - Debra Zaslow

You know what? I cannot be really tied to that answer because it was so long ago. It seems to me now that it was only a few days.

[00:35:27.020] - Dr. Gordon

Okay.

[00:35:27.570] - Dr. Lemanne

But do you think— and I don't know if you tried this— Did you, if you tried it for a longer period of time, would things kind of settle down? Would you have gotten into a new balance and those effects go away? Or do they, and this is for both of you, do those effects, as far as you can tell, you may not know if you just only took it for a few days, but do they tend to settle down? Do people get into a new rhythm and balance and their personality changes kind of fade back to their own baseline?

[00:35:54.930] - Debra Zaslow

I wouldn't have wanted to risk that because it would've involved a divorce. So I, you know, I did not try that.

[00:36:04.850] - Dr. Gordon

I would say in general, changes with testosterone for men or women typically come on slowly over day— over more like weeks at the very least. You know, I used this for a couple weeks and I began feeling this way. The exception and why I am not a fan of this protocol, there's a new approach to doing hormone therapy that wants to make sure that everybody gets tested for and offered hormone replacement if they want it, but they give it in pellet form. So I had a patient who was given— she was kind of in the setting—

[00:36:52.870] - Dr. Lemanne

Are you talking about an injection of a pellet under the skin?

[00:36:55.840] - Dr. Gordon

And it lives there for months.

[00:36:57.570] - Dr. Lemanne

You can't undo it.

[00:36:58.790] - Dr. Gordon

Exactly. And she, imagine this, Deborah, she got a testosterone pellet and within 5 days felt like you did and could not get it out of her system. It took 6 weeks for it to undo.

[00:37:14.180] - Debra Zaslow

Oh my goodness.

[00:37:15.780] - Dr. Gordon

Yeah, so I am not a fan of pellets.

[00:37:19.070] - Dr. Lemanne

Then they're used for estrogen and testosterone for, Well, that reminds me of anti-hormone treatments that we use in cancer. So in breast cancer, prostate cancer, we will give patients, and in transgender youth, we will give a shot of a medication that affects the brain and turns off the function of the gonads through the brain system. And, you know, called Luprolide, that's one of the most common ones. The brand name is Lupron. And those shots can last, depending on the dose and the formulation, can last from 30 days to 3 months. And that's what the package insert says. And in my experience, in older gentlemen especially, when we use it for prostate cancer treatment, the effects can last— the native testosterone does not return to normal levels sometimes 5 or 6 months after one of those injections. Very long-lasting.

[00:38:16.770] - Dr. Gordon

Variable, in other words, in its response.

[00:38:20.220] - Dr. Lemanne

And much more than the package insert says. Dr. Insert says is what I see quite a bit. It's not the 30 days or the 90 days. And so that's, you know, there are now pills that can be given. So you can take a pill every day and do the same thing. And that's much nicer. It's very expensive, however. And so a lot of insurance doesn't cover it. But if you need something like that, I think, you know, any kind of hormone therapy you at least want to start with a pill, or a topical, rather than a pellet that's injected and left there for months.

[00:38:55.430] - Dr. Gordon

And see where you're going with that. You know, can I take a little left turn here since you brought up treatment and following diagnoses of cancer? So we started out this conversation saying that it's now no longer, you know, a life sentence for the doctor or the patient to be, you know, sent to hell or whatever for considering or using hormones after breast cancer diagnosis or somebody at high breast cancer risk. Is there any way you could give us a little overview of if a woman's at risk from anything from DCIS to a history of personal cancer to a family history?

[00:39:39.370] - Dr. Lemanne

Yes, I certainly can, and it'll be a big overview. And again, I'm gonna give the warning that you, if you're considering hormone therapy after a diagnosis like breast cancer or prostate cancer, you must find and work with a doctor who is interested in that particular topic because you cannot do this yourself or with a doctor who just treats patients with general hormone replacement therapy after menopause, those kinds of things. So breast cancer comes in many different flavors and some breast cancers are are hormone sensitive and some aren't. That makes a difference. Some breast cancers are very advanced at the time of diagnosis. That makes a difference. Some breast cancers occur before menopause and others after menopause. Those are two different diseases and that makes a difference as to how any hormone replacement therapy would be even considered, much less approached, if you decided to, to move in that direction. The follow-up for breast cancer, especially if hormone replacement therapy is being used, must be very intense. And, you know, blood work, looking for circulating tumor DNA in some cases, other things that we won't go into here, but we can in a different podcast episode if our audience is interested.

[00:41:03.680] - Dr. Lemanne

So it's very, very— it has to be very personalized. As far as things like triple negative breast cancer, it's looking like many of those cases can take hormone replacement therapy without as much danger, but we're not sure. And you know, there's no such thing as a completely hormone receptor positive breast cancer or completely triple negative breast cancer. All of them are always in a mixture with certain populations of cancer cells being in the majority and that And that is the population that gives the patient a particular diagnosis. Oh, I have estrogen receptor positive breast cancer. Well, that means that most of your breast cancer cells are estrogen receptor positive, not all of them. And so there's a lot of ifs, ands, or buts, but I think that the FDA is moving in the right direction to say, hey, maybe we can think about this in a more individualized way and not condemn patients with terrible, not only symptoms like hot flashes and things like that, but terrible health, actually measurable health problems like cognitive issues, osteoporosis, heart issues, all sorts of things that are, that can be deadly from lack of hormones. We are no longer condemning those patients just because they've had a diagnosis of any, some type of breast cancer to putting up with those particular terrible disasters for their health.

[00:42:29.870] - Dr. Gordon

And do you— is it more their oncologist or their gynecologist that's going to help them navigate their risk?

[00:42:37.820] - Dr. Lemanne

It has to be both of them, and they have to work together. And the oncologist is going to drive the follow-up for the breast cancer in most cases, if the insurance will bear it. And that's an insurance issue. So, you know, who's going to pay, you know, which doctor is going to get paid for doing doing, you know, the follow-up and the work of taking care of a woman who needs special attention with hormone replacement therapy after breast cancer. So that's one of the things that plays into that.

[00:43:05.330] - Dr. Gordon

I will, you know, we share one patient who, gee, she's good 5 years out from her ER-positive breast cancer with you recommended intensive surveillance, and, you know, she's 5 years out and still doing fine and climbing mountains and You know, in her mid-80s, very glad.

[00:43:23.940] - Dr. Lemanne

And she's on—

[00:43:25.300] - Dr. Gordon

Hormone replacement, estrogen and testosterone, and I believe progesterone. I can't remember. I mean, obviously, if she has a uterus, she's on progesterone, but I don't offhand remember that part. But she's, you know, she got MRIs over the first 6 or 12 months, something like that. But now it's after the first couple of years, it's been routine surveillance. So she was very grateful. I was very grateful. And then you've also helped me. Deal with that breast cancer that isn't a breast cancer.

[00:43:56.300] - Dr. Lemanne

Oh, refresh my memory.

[00:43:57.430] - Dr. Gordon

That you told me that the OB/GYN at UC San Francisco actually now calls them— what's her word for DCIS that is not— Oh yes, I can never remember it, but it's atypical cells of epithelial origin, something like that.

[00:44:15.080] - Dr. Lemanne

Dr. Laura Esserman, a very brilliant a breast cancer surgeon who has been responsible for a lot of the downsizing of treatment for breast cancer. So lumpectomies, now sentinel lymph node dissections instead of removing all of the axillary lymph nodes, and even development of a vaccine for ductal carcinoma in situ, which is the process that you're talking about that can reverse it in some cases just by an injection into the tumor. The tumor itself. But you know what? I want you to say something about people who don't have a uterus and who do have breasts and hormone replacement therapy. You can just give them estradiol.

[00:44:58.850] - Dr. Gordon

That is right.

[00:44:59.900] - Dr. Lemanne

And you don't have to worry about increasing cancer risk and you don't have to give them progesterone.

[00:45:06.390] - Dr. Gordon

You don't have to give them progesterone. And there are reasons, There may be some reasons to do little judicious bits of progesterone if they have certain genetics and certain brain configurations. But yes, I mean, there are, you know, there are women who either have fibroids or just have trouble with erotic—

[00:45:29.580] - Dr. Lemanne

But no uterus.

[00:45:31.120] - Dr. Gordon

No, I'm saying who have— I want them to have perhaps a subtotal, but I want that uterus removed because it creates so many more problems of management. When, I mean, we're def— there's reason to leave our ovaries in later because actually our ovaries, and maybe this was your problem, Deborah, that your ovaries were still making so much testosterone, you actually just needed them fluffed up a little bit somehow rather than actually supplementing with, you know, our ovaries make testosterone and DHEA from pregnenolone our whole lives. And so we would like, it'd be good to keep the ovaries But we really don't need our uteruses after we've stopped having babies. And I think a subtotal hysterectomy, do you know about those where you leave the cervix so an orgasm is still relatively similar sensation as when you were intact? Do you know about subtotal hysterectomies?

[00:46:34.730] - Debra Zaslow

Are you talking to me?

[00:46:35.630] - Dr. Gordon

No, I was actually talking to Dawn.

[00:46:40.000] - Debra Zaslow

Subtotal hysterectomy is not my field. Ask me about personal narrative and storytelling.

[00:46:47.320] - Dr. Lemanne

Yes, I am aware of subtotal hysterectomy, but go ahead. You're doing— tell us about that.

[00:46:53.900] - Dr. Gordon

I had a— did you ever see the movie The Sessions with Helen Hunt?

[00:46:58.160] - Debra Zaslow

Yes.

[00:46:58.550] - Dr. Lemanne

Yes.

[00:46:59.290] - Dr. Gordon

Well, that is based on the true life story of my friend Cheryl. So when I saw the movie, I called her up and I said, Cheryl, that's you, right? She's a sex therapist and a, you know, a sex surrogate and a sex therapist, not a pregnancy surrogate, a sex— anyway, she works with people with sex, and she had a cancer that required her to have a hysterectomy, and she fought and championed her orgasms. And with a subtotal hysterectomy, keeping your cervix, you are much more likely to have persistence of your sexual enjoyment of you know, penis-vagina sex intercourse.

[00:47:39.950] - Debra Zaslow

But is that— I'm sorry.

[00:47:42.450] - Dr. Gordon

If you keep the cervix and get rid of the uterus.

[00:47:45.240] - Debra Zaslow

Is that because there's contraction of the cervix during orgasm?

[00:47:48.920] - Dr. Gordon

Yes. And it, you know, it's not going to be a perfect boundary line. It may not be the same sensation as with an intact uterus, but it's— she did a lot of research because she says, you know, this could ruin my career if I no longer like sex and that's my job. But it helped her. She became kind of an advocate and certainly instructive to me very early on in my medical career about subtotal hysterectomies for the preservation of sex.

[00:48:19.270] - Debra Zaslow

I have another question about that because you said penis-vagina sex, but I would say that any kind of orgasm can, you know, produce that contracting sensation. You are right. Whether the penis is involved anywhere or not.

[00:48:35.980] - Dr. Gordon

Yes.

[00:48:36.480] - Debra Zaslow

Okay.

[00:48:36.880] - Dr. Gordon

Whether there's a penis even in the neighborhood. Yes.

[00:48:41.610] - Dr. Lemanne

Well, I hate to leave this very titillating discussion, but I, you know, as we were talking about this and we're talking about when the uterus is absent, you have more freedom to prescribe estradiol because you don't have to worry about producing cancer in the uterus. Deborah, you know this, I'm very sure. There are two cancers that I can think— I know there's one cancer that we can think of that may be— the risk may be decreased with estradiol, and that is actually breast cancer.

[00:49:16.300] - Dr. Gordon

Yes.

[00:49:16.940] - Dr. Lemanne

So breast cancer incidence may be lower in patients who have simply estradiol and not progesterones or especially progestins, which seem seem— the latter seem to be particularly problematic in that regard. But there's another cancer in women that is much more deadly, much more deadly than breast cancer. We worry about breast cancer because it's so common, but most people don't die of breast cancer if they have it. But there's another kind of cancer that's so much more deadly, and that is colon cancer. Estrogen exposure seems to decrease the risk of colon I don't think we know why, but another topic for another day.

[00:49:59.000] - Dr. Gordon

Another topic.

[00:50:00.590] - Dr. Lemanne

Thank you to our guest, Deborah, Deborah Gordon-Zaslow. I just have to keep saying that because it's quite a coincidence. And to Dr. Deborah Gordon.

[00:50:13.110] - Dr. Gordon

And Dr. Dawn Lemanne. Thank you. We knew we were, we could go wide-ranging on this topic today and we did.

[00:50:18.080] - Dr. Lemanne

Write to us, write to us, audience, write to us and tell us what you want us to talk about. We will. We read all of our messages.

[00:50:24.980] - Dr. Gordon

Alrighty. Take care, everybody. Have a good week.

[00:50:28.280] - Dr. Lemanne

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[00:50:58.250] - Dr. Gordon

You have been listening to the Lemanne-Gordon podcast, where docs talk shop.

[00:51:04.020] - Dr. Lemanne

For podcast transcripts, episode notes and links, and more, please visit the podcast website at docstalkshop.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.

[00:51:40.200] - Dr. Gordon

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[00:51:52.310] - Dr. Lemanne

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[00:52:06.810] - Dr. Gordon

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[00:52:13.560] - Dr. Lemanne

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[00:52:31.090] - Dr. Gordon

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