Dr. Nanette Santoro Explains Veozah: Episode Link
TRANSCRIPT:
Welcome back guys. We are talking to Dr. Nanette Santoro and we, Bridgett and I have been waiting for this interview. We are thrilled to talk to you. Welcome to the show.
Thank you. Pleasure to be here. Well, it’s, we appreciate your time. We know you’re very busy and and I started to do some research. on these non -hormonal medications that are in phase three trials with the FDA and your name kept coming up.
Before we get started on talking about kind of these change -making medications that are going to be available hopefully soon for women,
I wanted to talk to you about the article that came out recently in the New York Times called Women Have Been Misled. Misled About Menopause and you were quoted in it and one of the things that I thought was really interesting was that you kind of were on the front line when the report came out from the Women’s Health Initiative in 2002 about kind of the negative information and risks and I wanted to find out from
you what was it like being a physician at that time with patients who are taking hormonal therapy? – Well, I think since that time, we’ve seen a lot of sort of wacky information campaigns where stuff that seems neutral immediately goes south and becomes this polarizing situation.
And that was really one of the very first times I had experienced that because I personally wasn’t prescribing hormone therapy. for the sole purpose of preventing heart disease.
I think that some clinicians may have been doing that. And I think with that came this profound sense of, oh my goodness, that wasn’t a good idea. Some people went into regret mode.
Other people went into hostile denial mode. No, that can’t be true. The study was wrong. And people got still stuck in prevention. world. And we’re unable to just take themselves out of that and go to people are having hot flashes, we need to treat them. Now we have a very good assessment of what risks may accrue to them with hormone therapy. Nothing was earth shattering, except the fact that it wasn’t protective.
Most of us expected it to be protective, but it wasn’t. So move on, you know, nothing to look at here, people move on, give hormones when they’re indicated, and don’t give them when they’re not.
So, you know, the communication of risk, and I really thought that the reporter on this article said it well, I mean, it was just a mess.
And no one could have predicted, I think at the time how it was going to go so badly. Many doctors had to calling in an absolute flop sweat panic.
You know, oh my goodness, you know, I’m taking poison. And I mean, just none of that’s true. And now that we have 18 year follow -up on the women who took these hormones for the most part overall,
there’s just no difference in long -term health outcomes. There are nuances to that data, but it again confirms that that this is pretty low risk stuff once you accept the fact that nothing,
there’s no free lunch and everything has some risk attached to it. So you kind of answered part of my question, what were your thoughts on that article because rich and I found it incredibly comprehensive,
as far as telling the history of hormone therapy, how the media has misled a lot of women into absolute panic and fear over taking medication that is hormone therapy.
What were your thoughts on the article? – Yeah, and I’m not sure I would blame the media. I don’t know that there’s any one person that or party that should be blamed. I think there were just a lot of things that were communication missteps that could we have done it better?
Yes. Many clinicians were angry, you know, that they weren’t told about it beforehand, but yet you’re running the study, how can you tell them beforehand without telling the women who are doing it?
So I thought that that was captured pretty well by Susan Dominus in the article, some of that chaos. And I think that some of the, you know,
some of the ways that everything got interpreted really have left us in a tough position. position. Many other treatments have come out that are bogus and that purport to be better.
They’re uncontrolled studies and, you know, we still have good old hormones that I have many patients that come in and just say, oh, I’m not going to take those. Still to this day.
Yes. And I find physicians to this day are not, not every but many and some that have happened to me personally. personally when I go and ask about this and I remember the first time I asked about this I was 47 years old and I was having hot flashes unbelievably just at night at least 15 times a day you know sometimes three times an hour hot flashes I asked about it and it just wasn’t even considered for me.
She thought I was too young she did the follicle -stimulating hormone blood test with that and said, “Oh yeah, okay, it looks like you are.” I was probably perimenopausal because I wasn’t 12 months out,
but was denied. I’m finding this to be a situation. I did find another physician that was very open to discussing this with me, and I wanted a hormone replacement.
Some people don’t want it. Do you find that it’s really hard to get the word out to different physicians that maybe this is not as risky as it had initially seen? – I think that that was also addressed in the Times article.
I think there’s a training gap that we’ve just had this turning away from hormone therapy so that the level of comfort with it is reduced. So a lot of people just don’t get enough training.
in OB /GYN. They get maybe six weeks of training and reproductive hormones and that includes menopause. There’s some training modules that they can take.
So you have to go out of your way to do it. And you know for example my colleagues in Family Medicine, we have many here at the University of Colorado who I inadvertently insulted with my quote in the article,
which I didn’t mean to do, but but what I really meant to say is most family medicine doctors have 15 minutes to spend with a patient. And if you’re going to have a lengthy discussion about hormone therapy, you really need a lot of extra skill training experience to be able to have that conversation and you probably need to make another visit.
I have a reproductive endocrine practice where I do a lot of what we call evaluation and management for menopausal patients. And those are not very well -paying visits.
So there’s a time disincentive and there’s a financial disincentive. And many doctors choose not to go there. Many fearless doctors still will do it.
And there are the North American Menopause Society, for example, has certified practitioners. These are people, they’re physicians, nurse practitioners, midwinter doctors.
PAs who have taken a specific interest in menopause and have gone to the trouble to learn it to go through the guide for learning. And those are places where women can find information that may help direct them to doctors who will be more sympathetic but you know you’re not the only person that I’ve heard say that I’ve gone to someone and they were just steps we were not just let’s not go there.
Thank you. Currently, there are two non hormonal medications that appear to be in phase three trials,
if I’m correct, that could help women with half flashes. And that can be a change maker. I know that you have been, your current research in menopause,
it was involved with one of them. I thought the best way for our listeners to understand would be would be to break down first, what is happening in your brain with a hot flash?
What research has shown with a hypothalamus and hot flashes? Could you break down and explain exactly what is happening in the brain when a woman has a hot flash? – Well,
I can’t explain it exactly ’cause it’s not fully known, but I would say that 10 or 15 years ago, there was, whoa, estrogen goes away, there’s this black box in the brain. brain. We have no idea what the wiring is.
And people get this, that we called it the thermoregulatory center in the brain. And we had a vague idea that it was located in the hypothalamus. So for those of you who haven’t heard of the hypothalamus ’cause not many people have, it’s sort of a waste, it’s a waste station in the midbrain and pretty much connects to everything else in the brain. So it’s a waste station in the midbrain. it was not particularly helpful to have that location of where it was until we came up with the candy neurons and by we I’m talking about Naomi Rance who was a neuropathologist in Arizona she noted that in animals and in humans that had had their ovaries removed this specific neuron in the brain the Kandy neuron it stands for Kispeptin, Neurokinin, and Dynorum. dinorphin. So chispeptin is one of the molecules that governs the reproductive system.
Neurokinin is sort of a pro inflammatory molecule. And there’s many, there’s a family of them. So that receptor was related to inflammatory processes and some connected to different nerves.
And dinorphin governs the endogenous opioid system in the brain. So these are all sort of pretty basic. basic functions and again in that midbrain that has many many inputs and many outputs but that finding led her to do some further experiments and there were beginning some other research that was coalescing saying these tachykinins which also can interact with neurokinin receptors were related in some women to a higher
risk of hot flashes and epidemiologic studies so the interest was accruing. She blocked that receptor with an antibody and found in animals that it seemed to eliminate hot flashes.
You can’t ask an experimental rodent if they’re having hot flashes or not, but there are ways to be able to tell. And in one particularly clever experiment done by another scientist, they created a tube where part of the tube was cold part of the tube was warm, and the animals had their ovaries out, If you had blocked the neurokinin receptor, the animals who had their ovaries out were all over the tube. They didn’t care where they went as long as that receptor was blocked.
The animals that weren’t blocked were all huddled at the colder end of the tube because they were having hot flashes. So it was a great way to tell that this was the problem. This is where it worked.
So it’s thought that there’s two places that have those neurokinin neurokinin receptors. One is in that area where the chispeptin neurons are in the hypothalamus,
and there’s a second set of neurons, interneurons that interact with that that seem to also have this neurokinin receptor. So we know that those neurons go increase with menopause,
they go up, if you block them, you’re going to be able to block, theoretically would be able to block. hot flashes. And it looks like it’s highly specific that it works as well as estrogen.
And that’s really what has doctors and clinicians really excited about it. Because the only other FDA approved medication for hot flashes is peroxitine mesolate.
It’s a long -acting salt of peroxitine, also commercially known as Paxil, but this compound is bristelle. And it works, but it’s not,
it just barely edged out the placebo effect, so it wasn’t of that order of magnitude. And every other treatment we have that we use off -label works a little bit,
but for most women, not nearly as well as estrogen. So now that they made this connection, scientists made this connection and presented it as an option,
first of the term non -hormonal is going to peak women’s interest because of the fact that they are so afraid to take hormones. Why did you get that to go into phase,
because I know that we were saying that it’s phase through trials, but how do you even get it to a phase one trial? Well, phase one is where you, that’s when you’re looking most. at that. Those are the very first experiments in humans for toxicity.
So you give it to a very limited number of people in phase one, and you just make sure that it doesn’t have any awful side effects. You go through a different doses. And you’ve already done all your animal research where you’ve shown that, you know, what dose kills half of the animals. So you’re kind of in the ballpark, you look at pregnancy outcomes in the animals. and you look at the molecular structure and try to figure out,
you know, is there going to be a problem with this? Does it have any particular configuration that it may be toxic to the kidney, to the liver, wherever, where do we have to look? So the many,
several compounds actually have gone through that, and there’s many others right now that are also in testing. Phezolinitant is ahead of the others. It is now actually with the FDA pending approval.
approval so we could hear any day now that it’s approved we could also hear that it’s not approved but I am a consultant for the company and on their scientific advisory board the data looks good that I know of and I’m hoping that it will be approved and we’ve just published a couple of new papers on it showing the safety and the effectiveness you know so many women they are like Colleen said just they they hear
the word hormones and they go back to the 2002 study and they are terrified. I would love to really, you know, wrap my head around who is really at risk for hormone replacement.
>> Yeah, important question because there are some women that should not take it. And most women are actually pretty low risk. in the 50 to 60 age group,
age range. But for some women who have had, for example, a blood clot of venous thromboembolism, that would be a deep vein thrombosis in the calf or a lung pulmonary embolus,
those women should not take estrogen. It’s generally recommended they don’t. Women who cannot take estrogen at all are women with breast cancer. The mainstay of treatment for breast cancer is giving an aromatase inhibitor, which which wipes out your estrogen levels and any estrogen exposure is thought to help encourage the cancer to mutate and grow. Women with endometrial cancer,
so there are some other rare estrogen dependent cancers where we don’t want to give hormones. Those are the biggest contraindications by far.
What about family history?
Because we hear from a lot of listeners, “Oh, my mother had breast cancer, my aunt.” had breast cancer, I can’t take it. What about people like that that have a family history of it?
Yeah, and it’s not in every case that you need to be afraid of hormones for that reason. So there’s a few objective ways that women can estimate the breast cancer risk.
Family history is one piece, the age at first birth is another major, major determinant of… and how many family members have it also makes the difference whether there’s any genetic mutations associated with it because it might prompt genetic testing.
And the amount of risk that hormones add to already high breast cancer risk is not always as high as people think it is.
So some women will still choose to take that risk because their their hot flashes are so miserable. miserable. So it is not an unreasonable thing,
and I will usually work with my patients, we’ll look at an objective breast cancer risk model, because then we’re just talking about a disease they do not have. Once they get a disease,
that’s a different story. >> With the trials in the phezo, I want to make sure I said that right, phezo and the phezo medication,
it was between women between the phezo and the phezo. ages of 40 and 70, correct? – I think it was 40 to 65. – 40 to 65, okay, let me try that again. So in the Phezo trials,
the women were between 40 and 65 and they had at least seven, I think the average was seven hot flashes. Were there any side effects that were noted during the phase,
during the trials? trials? They had at least seven hot flashes a day and amine of at least 50 a week because that’s the FDA guidance for hot flash studies.
So if you want to show that something’s effective against hot flashes you need to test it in sort of the biggest baddest hot flashers. So these women are they’re just on fire. I would have been a great candidate.
I would have been, yes. So they have to be tested, and I’m sorry, I forgot the other piece of your question. No, I was saying, what side effects,
if any, were noted during the trials? Yeah, because the trial was done during COVID, we had a lot of COVID related side effects, headache, body aches,
nausea, things like that. They seem to be distributed equally among the people taking placebo. placebo and Phezo, so really no side effects. There was noted in the early studies with similar related compounds and also with Phezo at higher doses that women reported back that they were sleeping better.
So in some of the newer studies sleep was incorporated and it does look like, we’ve presented that as an abstract, that there were some improvements in sleep and a paper is being prepared.
for publication on that. – That’ll be great news because we hear that from so many. – So many. – That’s another thing that comes along with menopause is the disturbance of sleep.
– Yeah, so that would be huge. And in one of the very early studies with a different compound, it looked like women were even losing weight with this type of compound. So I think I was high -fiving with one of my colleagues in the back of the room.
It’s like it’s the menopause polypill. But, you know, we need to see what happens when it gets out in clinical use. And we’re using it in all of our, the patients we typically will treat.
The women in the pheasant linotant studies do look like they were pretty much representative. About 20 % were African -American, about 20, 25 % were Latina,
and about a quarter had African -American. hysterectomy. So that’s pretty and based on their BMI was around 28, which is about the average BMI for women in that age group.
They seem pretty representative of American women. So that’s good to see. What about women that are already on hormone replacement? Would it be okay if they switched if they said,
oh, this, if this becomes approved, do do you know if it would be okay if they said, oh, I want to try this instead? Well, sure. I think it’s a completely reasonable thing. We’re giving hormones to alleviate symptoms.
So when we have another treatment, and often when I have a patient who has been on hormones for long enough that we feel like she’s kind of timed out, and she’s beginning to get risks that we don’t want her to have this may be something to switch, switch her to. – Once it’s approved, and we’re putting out in the universe that it will be approved. So we’re not even saying if, when it’s approved,
how do doctors find out and prescribe the medication? Because it seems like the doctors are a little delayed on information,
on menopause. How do we make sure that not only our listeners can ask for it, but that it’s an option that they’re given. There’s a number of ways that it gets delayed.
So first of all, it gets approved, but then it has to be costed out. Arrangements are made with insurance companies. Are you going to pay for this? If so, how much are you going to pay?
What’s the patient’s co -pay going to be? And then it has to get on the formulary. So a hospital formulary committee, like we have in our hospital in Colorado. or whatever, wherever it’s going to be prescribed by the insurance companies, they have to put it on their formulary. And that can take months. So that can delay it further. Cost can be a big issue. You know, I am a scientific advisor to Ustela’s.
The company is going to market it, but I do not have the capacity to advise them on cost. I have made my sentiments clear. I really hope this is going to be a further discussion. for women. But we have noted in the menopause field that many menopause treatments are not picked up by pharmacies.
Or if you you’re not the average patient and the simple stuff doesn’t work for you and you need a slightly more complicated treatment, it’s wildly expensive. So those things are pretty disappointing.
And, you know, we just don’t know yet where that’s how that’s going to fall out. So that can take time. Sometimes there’s there’s issues with physicians not learning about it.
And that’s part that’s part of that’s on the burden on the company is to get the information out. And that’s why they will bring detail people to doctors offices and practitioners to to,
you know, acquaint them with the compound and give them more information. But a lot of times those that that access has been restricted because there’s always worry about conflict of interest and giving physicians,
you know, to incentives to prescribe new, more expensive drugs. So those things can be barriers to getting the information out, but some of the reasons or the reasons behind it are good,
but it may make it take longer. – Are there any people, are there contraindications or contraindications? for the medication women who should not be taking? There are no contraindications at present.
Oh That’s great. That is great to know because that’s just the the most frightening thing for women and And another point that I want to make too that I’ve seen in some of your talks that I’ve looked watched on YouTube or the internet is that the treatment just of menopause that how it shouldn’t be really.
It’s not really a disease that it is a natural phase. Can you talk a little bit about that about how that can be an issue. Sure, I mean, you know,
there’s a lot of concern about the medicalization of menopause, and there’s also, you know, the messages that I feel are anti woman and anti feminist, and it’s highly gendered like oh women and their hormones,
you know. I think Rebecca Thurston said it well in the Times article, we seem to be comfortable and more comfortable with women suffering in our society than we perhaps should be.
And women don’t always speak up and agitate and advocate for themselves as much as they could. So I do think that having advocacy in this area would really be helpful.
–
Do you think that the FDA will make some type of decision soon or you just have no idea? (laughs) – If I could predict the FDA’s behavior,
I would be at the racetrack right now betting ’cause I could be at the middle of the time. (laughs) – Is it, I know the phase, I was reading about the phase two trials were in 2015,
2016. and then phase three, if I’m understanding correctly, started in 2019. Is it normal to take this long or do you think the COVID might have delayed? I think that’s actually pretty fast.
This is one of the encouragingly fast translations of the basic science into something that’s clinically useful. That’s something I wouldn’t know because I don’t know how that works.
And that’s what we want to know. you know, our listeners are your patients, are the women that come in and say, “I’m afraid to take hormonal medications.” And I wish I knew that there were medications that are going to be offered hopefully soon that can help my hot flashes.
And I think just finding out more about the fact that the hypothalamus and the neurons obviously were laid people, so it sounds a little Latin to us, but the more you know,
the more information we can give our listeners. Yeah, and we will learn a lot, you know, in post -marketing is sometimes where we learn a lot, and we do also learn about the weird and rare side effects that can happen.
So as of now, I would say probably we’re up to thousands of women that have been studied, but we’re not up to tens of thousands, and that’s when you can pick up anything that might be unusual or rare,
that may lead to further precautions or contraindications for the medication. But as of now, we have a good one year of safety on women and it looks quite safe.
Thank you so much for telling us about this and everything that you’re doing. And thank you for what you’re doing because it is is the physicians and the researchers that are coming out with this stuff that is actually going to make such a difference in women’s lives.
So thank you for everything that you’re doing. Oh, you’re very welcome. It’s really fun to do because it does make a difference in. It does. It absolutely does. And absolutely does.
And all of us who have lived through menopause appreciate all of this research. Yes. – Thank you so much for coming on. – All right.
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