July 17, 2025
Dr. Sara Brenner , Coordinator Of Meeting:
Introduction
– Good afternoon everyone and welcome to FDA’s White Oak Campus. This is our headquarters, and we are absolutely thrilled to have folks in the room joining us and folks joining us online.
We’re gonna go ahead and get started this morning or this afternoon, sorry, we are gonna hear a lot of great things from our experts at this round table. But first I’m going to hand it over to our commissioner, Dr. Marty Makary for some opening remarks and comments. –
Dr. Marty Makary, FDA Commissionera:
Great, thank you Sara, it’s so good to be here.
It’s so good to see everybody. So great to meet all of these experts in person. I have read the work of so many of you, so thank you for being here and contributing. This is a very important issue. In the 1950s, researchers at the Mayo Clinic noticed that women who had their ovaries removed in their 20s all went on to have early heart disease, including a fatal heart attack. Let me start over again.
I don’t know if you had that. I don’t know if you could hear me in the back. In the 1950s, researchers at the Mayo Clinic looked at women who had their ovaries removed, and they noticed that they all went on to have early heart disease, including one woman, who had a fatal heart attack at age 28, suggesting a powerful and profound cardioprotective effect of estrogen made in the ovaries.
Other studies went on subsequently to show that when a woman starts estrogen or estrogen plus progesterone, within 10 years of the onset of menopause, there is somewhere between roughly a 25
and 50% reduction in fatal heart attacks and cardiovascular disease.
Now, just to put that in context, that is comparable to the risk reduction or greater than the risk reduction of a statin, heart disease is the number one cause of death in women.
And a 2015 Finnish study found that when women taking HRT
stopped taking the hormone replacement, the risk of a fatal heart attack went up by 26% within that one year that they stopped taking it. What’s going on here? Well, there’s some significant nuance that is for women, who go without hormone replacement therapy for greater than 10 years or without natural intrinsic estrogen production
for more than 10 years, the benefit can turn into a risk because there may be progression, of atherosclerotic changes in the cardio vasculature. Some doctors recommend never prescribing hormone therapy in initiation of therapy after age 60. There are many different practice styles out there.
We’ll hear from the experts today, but there is nuance to affirm
this idea that if a woman is to start it, if they do not have a contraindicationm, or a relative contraindication, that it is important to start it within 10 years of the onset of menopause, or before age 60 roughly. Now, I don’t practice in this field.
I’ve been observing the medical literature, but this nuance was affirmed in the 2002 Women’s Health Initiative study where the average age of starting hormone replacement therapy was over age 60.
It was age 63 on average. That’s too late in the minds of many experts.
In fact, a 2017 reanalysis of this data by Manson et al and JAMA
found that in the group under age 60, there was a decrease in all cause mortality among the women that took hormone replacement therapy. Now, that 2002 Women’s Health Initiative study suggested that there was an association with breast cancer.
Doctors called their panel of patients to tell them to get off of it immediately.
The many benefits of hormone therapy were ignored as it was seen as a carcinogen.
Prescriptions for hormone replacement therapy plummeted in the United States. Women flushed their pills down the toilet. The amazing thing was that in that 2002 paper, there was no statistically significant increase in breast cancer mortality, amazing.
But as a result of the fear of breast cancer, 50 million plus women have not been offered the incredible potential health benefits of hormone replacement therapy because of medical dogma.
One of those women was my mother who went through perimenopause around that time.
She went on to have a couple bone fractures subsequent to that in the course of her older life.
So I was struck when I learned that hormone replacement therapy started within 10 years the onset menopause reduces the risk of bone fractures by up to 50%.
That’s a New England Journal of Medicine randomized controlled trial. And remember, when a woman gets over age 80, the risk of a fracture can be fatal. One in three women over age 80 will have a hip fracture,
and the one year mortality is 22%. Bone strength matters, and that of course is another well-established long-term health benefit, is the reduction in bone fractures.
It has also been found to reduce cognitive decline by up to 64% and in one study reduces the risk of Alzheimer’s by 35%.
And we’ve got billion drugs that are aimed at slowing the progression of Alzheimer’s.
But there may be a hormonal association whereby there may be a benefit in preventing Alzheimer’s at a much lower cost.
Notice I’ve only been talking about long-term benefits and not the short term alleviation of the symptoms of perimenopause experienced by many women. Symptoms that can be alleviated, including mood swings, difficulty sleeping, dryness and maybe 50 plus other potential symptoms of perimenopause. Today we are interested in learning and that is why Dr. Brenner and myself have convened incredible experts on this topic, well published with impeccable credentials to separate medical dogma from evidence.
So I look forward to learning from all of you. I would be very interested in your thoughts on what we discovered when we came to the FDAA few months ago.
Number one, there is a black box warning on vaginal estrogen.
Even though the North American Menopause Society and the American College of Obstetrics and Gynecology has called for removing it, we discovered that there is a black box warning
on systemic estrogen, even though no clinical trial has ever found
an association between hormone replacement therapy and an increase in breast cancer mortality.
So we want to learn from all of you, update us, teach us about the latest evidence and help guide us as we think through what should be done here at the FDA. Thank you very much for being here.
Dr. Sara Brenneraaaaaaa:
– Fantastic, excellent. All right, thank you for those opening remarks. So we have a lot to dig into here today,
Ground Rules
and I have the dubious honor of setting out the ground rules. So I’m gonna introduce folks first, then I’m gonna tell us, the folks in the audience and listening online how the event is going to play out and we’ll get started.
So I would like to welcome Dr. Heather Hirsch, Dr. Barbara Levy, Dr. JoAnn Pinkerton, who will also be presenting on behalf of Dr. JoAnn Manson, who can’t join us unfortunately today.
Dr. James Simon, Dr. Philip Serrell, Dr. Roberta Diaz Brinton, Dr. Vonda Wright, Dr. Kelly Casperson, Dr. Mary Jane Minkin, Dr. Rachel Rubin, and Dr. Howard Hodis. Welcome and thank you for being here.
Please note that the personal opinions and expert views of those panelists who are speaking today do not represent FDA’s official position. Before we get started, here are the housekeeping items.
So the panel is being recorded and live streamed to the public is viewable on FDA’s YouTube channel and on X, thank you to our outstanding crew here making that possible in the room. The recording will also be available following today’s panel, so folks can go back and listen, or listen for the first time if you’re not with us right now. We’d also ask for folks listening in the room, including media, to remain in listening mode only. Each expert presenter will have five minutes for a total of 60 minutes to cover any topics they would like to share with us and the public.
And I have this handy dandy red, yellow, green blinger here today to keep folks honest on their time.
So we do ask you to make sure that you limit yourself to five minutes. After that, we will go around and have questions
and I can pose those to you or you can pose them to each other and we’ll have a sort of lively discussion
for about 45 minutes before we close out today. All right, so first we’d like to hear from Dr. Heather Hirsch.
Dr. Marty Makary, FDA Commissioner
– [Speaker] State any conflicts of interest first? –
Dr. Sara Brenner
Okay, good, one other quick thing, Dr. Hirsch. And for all of our panelists, the on, off button for your microphone is here. When the red light is on, you’re on. Easy, on, off. And the other thing we’d ask you to do is state clearly any conflicts of interest you have before you present, go ahead.
–
Dr Heather Hirsch:
Well, good afternoon, I’m Dr. Heather Hirsch. I have no disclosures.
I am a women’s health fellowship trained board certified internist,
and on behalf of the entire menopause expert panel, I would like to say we are honored and excited to be here for this life changing conversation.
Our purpose here is clear to provide concise and logical information in support of the safety of menopausal hormone therapy. I completed two years of advanced women’s health training at the Cleveland Clinic, and during my training, I poured over the research only to find something earth shattering. That history got it wrong when it comes to menopausal hormone therapy. Now we at times want to be logical,
but may also be emotional because we have seen the life changing impacts that menopausal hormone therapy has had on women. For me, it was my patient, Denise, in the middle of perimenopause, she woke up one night covered in vasomotor symptoms, alerted her husband and said, I’m having intrusive thoughts of harming myself. And he took her right to the emergency room.
We are harming women by not having clear facts, and this is really important to discuss today.
As we redefine harm, let’s start by making some definitions.
Local, vaginal or also sometimes referred to as topical estrogen is estrogen that is placed inside the vagina and is FDA approved to treat genital urinary syndrome of menopause, which is painful intercourse or vaginal dryness, as well as recurrent urinary tract infections.
Importantly, and we will discuss this today during the expert panel, this medication does not travel systemically.
That means it does not go through the entire body. What we know is that it does not increase the risks of heart attacks, breast cancers or strokes. No data shows that, however, there is a boxed warning
inappropriately affirming that it does. Menopausal hormone therapy is the combination of an estrogen plus or minus a progestin or a progesterone if a woman has an intact uterus with or without the addition of testosterone. The trouble with the term menopausal hormone therapy is it is poorly defined and very broad. What you’ll hear today is that there are specifics that matter.
The route is important, meaning is it taken orally or is it taken transdermally on the skin.
The formulation is important, meaning it’s chemical structure and the time at which it is taken is also very crucial.
Hormone replacement therapy is indicated for women who’ve had menopause before the age of 40 or 45, and is a medical necessity. A boxed warning, formerly known as a black box warning, is the highest safety related warning that can be placed on a medication by the FDA.
By definition, this means that the medication can incur serious and or life threatening adverse events.
This makes patients and clinicians afraid of these medications
and it may be extraordinarily unnecessary as we’ll see from the evidence today. With my two minutes remaining, I wanna make three clear and concise points. Number one, vaginal or local estrogen
is categorically safe for all women, period. Because it does not travel systemically, there again are no increased risks of heart attacks, clots or strokes, and the black box warning is wrong and should be removed. Number two, systemic hormone therapy has warnings
again that are broad and poorly defined. We are going to discuss important points today such as the facts that in the Women’s Health Initiative or the WHI, estrogen alone decreased the risk
of breast cancer statistically. And when we swap or switch the progestin in the WHI for different formulations of progesterone, we do not see any increased risk of breast cancers above baseline and transdermal estrogen has not been shown to increase the risks of clots and may reduce the risk of cardiovascular disease if started within 10 years.
And number three, the gaps in training magnify the damage.
Many clinicians receive an hour of menopause education
potentially like me, which was a voluntary lunch and learn lesson.
This is crucial that we support clinicians and healthcare professionals in prescribing and managing FDA approved hormone replacement therapy with ease and confidence.
I am excited to hear this panel today because I do believe we are doing harm in the name of do no Harm, and this is affecting 50 million women at any time who are between the ages of 40 and 60.
Women deserve policy that reflects the current evidence and not outdated myths.
Dr. Sara Brenner:
Thank you. – Very good, thank you Dr. Hirsch.
Dr Barbara Levy:
All right, our next panelist is Dr. Barbara Levy, go ahead. – Thank you so much, Dr. Makary for convening this panel.
I was really excited to meet some of these people in person for the first time, but I wanna share with you my sense of doom in July of 2002. I have PTSD from that day when the NIH press conference occurred, I can tell you where I was.
I can tell you what I was drinking, which was soda water. I was on my way back to Seattle where I practiced from an ACOG committee meeting. And I can tell you the devastation of the patients in my practice. The phone calls, the just overwhelming upheaval of everything that happened over the next 20 plus years now. It has been a huge harm for women.
My disclosures are on the form here.
My key points, not all hormones are the same. So the Women’s Health Initiative studied conjugated equine estrogen
or medroxyprogesterone acetate. Two very explicit and specific drugs
that were used in the 1990s in my practice all the time.
It’s very important to understand that estradiol, 17 beta estradiol, which is the natural to human estrogen, binds receptors differently than conjugated equine estrogen. And it’s inappropriate scientifically
to conflate the results in a study that used conjugated equine estrogen to all forms of hormone therapy. That is just a disaster that we’ve been perpetrating for decades now.
So to classify all hormones as the same, either the benefits or the risks,
is completely inappropriate. And as Dr. Hirsch said, root matters whether it’s transdermal, oral, vaginal, makes a difference, dose makes a difference. We can kill people with aspirin and it’s over the counter.
So dose makes a big difference in how we do the studies and what we’re looking at. So not all hormones are equivalent.
As Dr. Hirsch said, micronized progesterone, which is the natural to human progesterone, binds receptors very differently than medroxyprogesterone acetate.
We need to stratify studies of menopausal hormone therapy by the age of the patient. As Dr. Makary mentioned, starting at perimenopause or early menopause, very different than starting women in their late 60s and 70s.
And honestly, researchers at the WHI were asking a legitimate question, should we start all women at all ages on hormone therapy to prevent cardiovascular disease?
That was the question. And they purposely enrolled older women
to power the study appropriately. So it wasn’t ever about symptoms,
it was really about cardiovascular disease and to get enough people with enough heart disease.
That’s why we see that the average age was 63, which has nothing to do with the patients in my population that are coming in in their 40s and 50s. So all of our studies have to be stratified by age of the patient, by dose, by formulation, by root of administration, very, very important.
Initiation of menopausal hormone therapy does not address the issue of continuation beyond age 60.
So the conclusions from the WHI and the harm that was seen in women who were mid 60s is not the same as someone who starts at menopause or perimenopause and continues hormones throughout.
Receptors change, a lot of things change, and many of us will talk about this, but the harm because of that start within 10 years
and under age 60, has perpetuated a very dangerous situation
where the American geriatric society has placed menopausal hormone therapy on a list of drugs that are potentially hazardous to the elderly. And that places those drugs then in measures and other areas that create barriers. We have to look at matters that matter,
impact on sexual function, cardiometabolic health, mental health, bone health, women are whole human beings.
We’re not a heart or a breast or a brain. We’re whole human beings. And all of our studies need to consider women as whole human beings. And finally, we have to make our clinical decisions on things that matter.
And that means preservation of function. So most of us would agree that we don’t use menopausal hormone therapy to treat cardiovascular disease or Alzheimer’s disease or osteoporosis, but prevention is so important and preservation of function is absolutely key.
And those are the things we should be looking at, thank you.
Dr. Sara Brenner:
– Excellent, thank you so much. Our next presenter is Dr. JoAnn Pinkerton, also presenting for Dr. JoAnn Manson.
Dr Joanne Pinkerton:
– So I’m gonna start by being the voice of Dr. Manson who wanted to be here.
She is at the Endocrine Society out in San Francisco, but she really wanted to present her data to show how to combat this misinformation because just like Barbara, when the WHI came out in 2002, the phones rang off the hook. I had an open session. 600 women showed up just frightened to death that they had taken something that was gonna kill them or give them dementia. And so they suffered and 25% went back on.
But this data that I’m gonna show you is come from two parts. Wait, somehow we, yeah, okay.
I’m gonna talk about primarily in the WHI trials that were starting.
On average age woman is 63, but she divided it out and you can’t see this, but she wanted this data presented.
At the very bottom of the slid there are three columns. The first one is age 50 to 59, the second one is 60 to 69, and the third is 70 to 79. The estrogen is in blue, placebo is in orange.
And if you look on the left at that slide, you see very few absolute events.
You do see benefits in terms of fewer breast cancers and less mortality, but very few events in that group.
If you jump all the way over to the right hand group, that is the women starting at age 70 to 79 when they might already have cardiovascular events or heart events. And what you see is an increase in heart events and in stroke and in total mortality. So that differentiation started to happen, but it didn’t happen until 2013. And then in 2017, based on this next data that I’m gonna show, we rewrote the NAMS position statement. And with that, we said, let’s look at just those women that we wanna start hormones on. The women under age 60 within 10 years of menopause. So the top of the slide is the conjugated equine estrogen and the synthetic medroxyprogesterone acetate trial. And the second table is the conjugated estrogen alone trial. And what you see when you have conjugated estrogen and you add progestin, the risk are in purple
and you can see them at the top and you’re gonna see an increase in heart events, stroke and blood clots, but very small numbers in this group. And then the benefits in terms of breast cancer and the all fractures, all cancers and all cause mortality and diabetes, those things went down.
They didn’t go up. When you look at the CEE trial, you’re gonna actually see more dramatic benefits because estrogen alone has a very different effect than when you combine it with the progestin.
And you’ll see that the heart events, they went down instead of going up, we saw a slight increase in blood clots because it’s an oral product. We saw, again, a true decrease in breast cancer, fewer cases, decrease in fractures, decrease in all cause mortality and a decrease in diabetes.
So I really want you to focus on that data because what we’re telling you is that if women are between 50 and 59, the outcomes are more favorable in that young age group and also more favorable for estrogen alone than the synthetic progestin. They only looked at one formulation.
You’ve heard transdermal is different. You’ve heard progesterone is different from the synthetic progestin, but that’s not what was tested in this trial and everything and every warning that is on systemic estrogen is based on this trial and the data across the board, not the data that ought to be being put out, which is the data from 50 to 59. And E alone is significantly better for younger women in terms of heart attacks, all cause mortality and the global index than women who are 70 and over the long term, which I’m not presenting that data, but what they found was that estrogen alone led to a reduction in breast cancer incidents and a reduction in breast cancer mortality.
Estrogen and progestin did not show an increase in breast cancer mortality, although a slight increase in breast cancer risk.
And what we know from the French E3N study is that there’s less risk when you add progesterone than the synthetic progestins. So Dr. Manson, thank you very much for your data and all the work that you’ve done.
And then I’m gonna switch over and become myself. So now I’m Dr. Pinkerton
and I was the past president of NAMS and Executive Emeritus Director and here to talk about this.
And what I want you to think about is my patient, Joyce. So she’s had genital urinary syndrome of menopause.
I’m gonna call it GSM and I’ve tried to help her. She stopped having sex because it was so painful.
This year she comes in, she’s having recurrent urinary tract infection. She’s had three in the past year. One of them made her really, really sick.
She almost was septic and so I convince her I do a vaginal pH. I show her that she’s got a pH of seven.
I talk about all the changes. She says, I’m gonna do it. I’m gonna do it this time. Dr. Pinkerton, she goes home, she pulls out the tube of estrogen and it says, warning endometrial cancer, cardiovascular disorders, probable dementia and breast cancer.
She looks at it, her partner or spouse looks at it and they throw it in the trash because they’re afraid that improving their sex lives is gonna cause breast cancer, dementia or death from heart attack or stroke.
Why is sex important if it’s gonna kill me, to be able to do it? So I wanna make the point and I know that Heather said this,
but the boxed warning is not supported by science. It harms women.
It reflects an estrogen class labeling, which was extrapolated from the systemic hormone therapy trial that I just showed you average age 63, it overstates risk. There is an absence of randomized clinical trial
or consistent observational evidence linking vaginal estrogen to GSM, to cancer, heart disease, dementia, blood clots or stroke. And if you look at blood levels for systemic hormone therapy, they are dramatically higher than the levels we see with these local vaginal estrogens dose to treat GSM. So Dr. Santon has shown that our basal estradiol levels when were postmenopausal range from one and a half to 12 picograms per ML, median of 4.5.
When he looked at all of these low dose therapies, the range was four to 14 picograms per ML.
Notice that that’s essentially the same. The vaginal ring goes up to 19 on day two and then is not detectable for the next three months in women. And so therefore, whether it’s a vaginal tablet, an insert the ring dosed for GSM or the creams that are dosed low, we do not have any biological mechanism to explain how it could cause heart disease or a stroke or blood clot or dementia. And then I wanna show you a recent paper. It was published in the American Journal of OGYN in 2025 by Bestie. She did a systematic review and a meta-analysis and looked at women who were on breast cancer using these low dose vaginal therapies for GSM.
If you look the risk line, the hazard ratio is that black line going right down the middle.
If you’re on the right, it increases your risk. If it’s on the left, it decreases your risk. The studies were all on the left.
A few of them approached one, which means it’s not statistically significant. But then when she put them all together,
she saw no increased risk of a note on particular slide is on the recurrence of breast cancer, but she also shows in her paper no increased risk of breast cancer recurrence overall mortality in women
with breast cancer using these vaginal therapies. Endometrial safety’s been shown by Dr. Crandall.
Systematic review trials up to 52 weeks, no increased risk. So I am begging the FDA and all of us are begging,
please remove the box label. Put a warning if you bleed. You need to be evaluated for that rare risk of endometrial cancer.
If you’ve had an estrogen sensitive cancer, please include your oncologist and please stop harming women.
– (Thank you, thank you very much for both of those presentations. I noticed they did give you 10 minutes. I was hoping they’d give five and five and they did it.
– [JoAnn] And they did. – And they did, and it was two JoAnns, so it really kept us going. – [JoAnn] Very different JoAnns.
– All right, fantastic. Our next panelist is Dr. James Simon, go ahead please.)
Dr. James Simon:
– So Commissioner Makary, deputy Commissioner Brener, I’m tasked
with taking my three colleagues who spoke before me and making it simple for everyone to understand.
I’m gonna speak specifically about the class label on local or low dose vaginal estrogen products.
And freely admit that the FDA has a very complicated, often time difficult balancing act in constructing a label that’s understandable,
that’s straightforward, and that carefully and correctly balances risks
and the benefits of a given product. I believe that in terms of the low dose vaginal estrogen label, they have failed.
Let’s talk not all about all the characteristics and problems in constructing a good label.
I’d like to talk only about two of them. The first is the label should be consistent, not only with the product and the data presented on the product to the FDA, but also consistent with the scientific literature. You’ve heard some comments to this effect.
In addition, the other characteristic I wish to talk about is that the label for a particular product needs to be consistent and fair with other products used for the same treatment.
Let’s not have the FDA giving a label that artificially gives more value
to one product than another or another product to the same product. That’s for the business environment, not for the regulators.
So I’d like to speak and expand to some comments that Dr. Pinkerton made as a good introduction.
Here you see on the upper left an FDA approved product, IMVEXXY, four micrograms delivered vaginally.
And at the bottom, Intrarosa, a different product, not an estrogen by characterization and its label. Since the Women’s Health Initiative in 2002 and subsequent class labeling changes, all estrogen products contain class warnings.
In brief and listed here, they include the vaginal estrogens
can cause or be associated with stroke and dementia, namely the brain, heart attack, myocardial infarction, namely the heart, breast cancer, IE the breast, deep vein thrombosis, pulmonary embolism and cancer of the endometrium.
Now, in order for estrogen to get to those organs, we presume it has to go from the vagina into the blood and jump to the brain, the heart, the breast, et cetera.
That’s logical, or to me it’s logical, but in fact it doesn’t do that. It just doesn’t do that.
And when you measure estrogen as a result of placing these low dose vaginal estrogen products in the vagina, you cannot measure them in the blood. You cannot measure them in the blood.
Maybe I’m not clear. You cannot measure them in the blood. So you cannot interpret the delivery of low dose vaginal estrogens as causing all these things that are horrible, painful,
that keep patients from using the products when they need them based on their blood levels.
So finally, the FDA requested that the makers of these products do large randomized trials, which they could not do. But large observational trials were done by the market leader in this case.
I presented those data at the International Menopause Society meeting last year on some 400,000 patients studied in the US and 200,000 patients studied in Denmark with no effect on the endometrium. And the endometrium is the first to be affected by vaginal placement.
So let’s look at consistency. The last consistency is these two products.
The second one, Intrarosa, listed here on the bottom. And it has exactly the same blood levels as the IMVEXXY product listed on the top. And the contraindications, and I’ll list them, undiagnosed, abnormal genital bleeding.
Any postmenopausal woman with undiagnosed persistent or recurrent genital bleeding should not use the product.
And anyone with a past history of breast cancer should not use the product. But no heart attack, no stroke, no dementia, no deep vein thrombosis, the same blood levels. So the label needs to be changed
for low dose hormone therapy. It’s not consistent with other products and it’s not in any way, shape or form logical, consistent or reasonable given the scientific literature.- [Speaker] Thank you. – Thank you so much, yes, our next presenter can go ahead.
Dr Philip Sarrel:
( Yep, Dr. Philip Sarrel go ahead. )
– My hope is that from my presentation, you will develop a deeper feeling for what a woman experiences at the time of menopause estrogen deficiency and a greater appreciation for how important this particular molecule is in biological existence. Estradiol effects are seen in most of the body’s cells, including the brain where it has been referred to by one of our speakers later this morning,
later this afternoon, where it has been referred to as the master regulator in the brain.
Symptoms of estradiol depletion due to disturbed brain function include loss of temperature control, sleep disturbance, cognitive disturbance, mood disorders and angry outbursts.
These symptoms can affect a woman in profound ways.
Her sense of self, her daily functions, her relationships with her spouse.
The effects of these symptoms in working women, in working women is a subject of current interest.
In a six month placebo controlled study done at Yale, 68% of 78 women with severe hot flashes reported negative effects on work ability. At the top of this list were trouble remembering, 82%, and sleep disturbance, 80%.
Trouble remembering was reduced to 26% and sleep disturbance to 10% after six months of daily estrogen. Other symptoms affecting 50%
or more of the women included checking and double checking and doing tasks so slowly to ensure correctness. Both of these symptoms were reduced to 8% after estrogen therapy. Temper outbursts at work
were reduced from 34% to 6%. The women included a banker considering retirement because she could not remember the names of her board of directors and a waitress who broke dishes in angry outbursts during her workday. I’m glad to report that both were restored to their normal selves after the six months.
In another study having to do with work, we reviewed the insurance claims over the course of one year for working women with and without hot flashes.
The women all worked for Fortune 500 companies. There were 252,273 women in each group.
The women with untreated hot flashes had one and a half million,
million more visits for medical care. The costs for healthcare and work loss were $400 million more than for those without hot flashes. Now let’s turn to another issue, death.
That’s a pretty distinct issue. Death attributable to avoiding estrogen.
By age 50 half women in the United States have reached menopause. A third of the women in the United States have had a hysterectomy by age 50. In 2011, WHI reported, quote, women age 50 to 59 who received conjugated equine estrogen compared to women who received placebo had 12 fewer myocardial infarctions and 13 fewer deaths per 10,000 women. These WHI women who died were all under the age of 70.
This was a 10 year follow up. They’d been 50 to 59 when they started. They were 60 to 69 at the end when this was reported.
Our team at Yale used those numbers and the percent decline in use of estrogen therapy to calculate that almost 50,000 women in the United States had died between 2002 and 2012 because of avoidance of estrogen.
In the years since our original calculations, another 100,000 women have died in their fifties and sixties, died in their fifties and sixties because they didn’t use estradiol replacement after hysterectomy at the rates for women prior to 2002.
More recent WHI ( Note: Transcrpted Error. Should be WHI, correction from AI), reports of data for women age 50 to 59 receiving estrogen only show an all cause decrease in mortality of 32% with decrease in mortality due to cardiovascular disease, hip fracture,
breast and colon cancer. Yes, decrease in the women who took estrogen and a decrease in deaths from dementia. Yet as Dr. Manson has stated in her papers, only 4% used hormone replacement afterwards.
Now what I need to show is, how do I advance? Oh, this way.
Okay, so now let’s just take a look at the bottom of the slide ’cause I love the octopus. And the octopus is so interesting.
This is a organism that has lasted for 600 million years. 600 million years ago, the octopus discovered estradiol. It was the very first steroid to evolve in the course of history and it put the estradiol to work.
The octopus is made up mostly of brains and hearts, nine brains, three hearts, no breasts to worry about, no skeleton to worry about, no skin to worry about, the octopus just makes its way in the world with what it’s got. But what it’s got is something that oils the system, that connects the circulatory system and the nervous system and keeps them working together well through the course.
For example, by inducing nitric oxide in the octopus, estradiol enables it to have facial recognition.
It’ll memorize your face, and when you come back again, it will come to you because it knows you.
And that’s enabled by the nitric oxide induced by the estradiol.
That’s important. Skin color, melanocytes, one of our professors at Yale 50 years ago discovered that melanocytes, in order to tan need estrogen.
Without it, the skin burns. That’s an interesting difference at menopause.
So but the octopus uses skin color as a defense mechanism and that is dependent on estradiol.
So through the course of evolution, thousands of cellular actions
of estradiol have emerged, giving the hormone a major role in biological existence.
What I’ve presented are highlights from three different full lectures on each of the topics.
Hopefully we will have an opportunity to discuss them more fully in this session that follows.
Dr Roberto Diaz Brinton:
– (Thank you. – Wow, outstanding, thank you so much. All right, moving on.)
Dr. Roberta Diaz Brinton, please go ahead. – First, let me add my thanks to the FDA for the invitation to discuss our research on estrogen action in the brain.
These are my disclosures and I want to particularly point out the support from the NIH, National Institute on Aging, who’s supported this research for quite a long time that I will be presenting here.
2/3 of all women, Americans and worldwide, of Americans with Alzheimer’s disease, 2/3 of them are women. And it was really one woman with Alzheimer’s disease who transformed my scientific career. She could not remember me for 30 seconds and I’ve remembered her for over 30 years.
And why does that occur? It turns out that our research has shown
that it’s not because women live longer than men by 4.5 years.
It’s because the disease can start earlier in women during the menopausal transition when the brain undergoes a substantial loss in the ability to utilize glucose as its primary fuel.
This work, our basic science research, was supported by human FDG
PET and MRI imaging conducted with our collaborator Lisa Moscone at Weill Cornell, which shows that the brain undergoes, the female brain during the menopausal transition undergoes a decline in glucose metabolism and a coincident rise in the deposition of beta amyloid in the brain during the same timeframe.
There is a small but not specific loss of gray matter, not beyond the normal aging.
What there is, however, is a decline in white matter, those connections in the brain that enable communication across all neural circuits in the brain, giving rise to some of those symptoms that women can experience, the whatchamacallit syndrome, the inability I know to recall names, recall information. We have also focused on understanding the hot flash.
And the hot flash is actually induced by the generation of brain heat.
And that heat is generated by the change of mitochondria from highly efficient to inefficient.
And I think many of you’ll recognize the meme that is there of a woman who is experiencing a hot flash
at a football game. And you could see that the heat is emanating from her head.
And right below is the brain. What we have also conducted is medical informatic analysis to really address the question, is hormone therapy, menopausal hormone therapy associated with reduced risk of developing age associated neurodegenerative diseases? And here what you see is hormone therapy is associated with a reduced risk of Alzheimer’s disease, Parkinson’s disease, all cause dementia, multiple sclerosis and ALS. Now there’s, as you’ve heard, much controversy over the impact of hormone therapy. And what our research has shown is that the brain is indeed changing, that decline in glucose metabolism activates a starvation response that leads to utilization of auxiliary fuels.
And that auxiliary fuel is provided by the white matter. The brain will utilize its own white matter, catabolize its white matter lipids to generate ketone bodies.
And what we see is that depending upon when hormone therapy is introduced, whether as been spoken about previously, when introduced at the time of menopause and for menopausal symptoms, there is a significant reduction in risk of developing Alzheimer’s disease.
Whereas when the brain has undergone this decline in glucose metabolism, a rise in inflammation in the brain, there’s an increased risk of developing Alzheimer’s disease. And the gap that we still have
in the menopausal hormone field is really applying precision medicine approaches to precision to generate precision hormone therapy for all women where appropriate.
Thank you. –
( Very good, thank you. Our next presenter is Dr. Vonda Wright.)
Dr Vonda Wright:
Go ahead, click your mic. Yep, click your mic, there you go. – Thank you so much for having us today.
I have no relevant conflicts of interest. I’m a practicing fellowship
trained double board orthopedic surgeon and clinical researcher in musculoskeletal aging. And before that I served women at the bedside as a cancer nurse. So I’ve been taking care of women for nearly 30 years and in these 30 years I’ve probably taken care
of 100,000 people as a physician. And so looking 100,000 people in the eye gives me a deep sense of what they need in their suffering. And when I’m on call now, I frequently meet women in the ER such as Miriam. They have broken their hips.
This is the rod that I put in Miriam’s hip. This is only one of many kinds of metal screws, plates, implants that I use to treat their hips
because of a condition osteoporosis that is largely presentable.
There are approximately 80 million women in this country over 40 and up to 40% of them will develop osteoporosis.
This is a rate four times that seen in men and occurs 10 years earlier than in men.
And osteoporosis is not just the slow, steady state decline seen with aging.
This, according to the endocrine society is a sharp, precipitous drop in bone quality where we lose 15 to 20% of our bone density in the five to seven years surrounding our perimenopause.
The exact time when we’re losing our estrogen, one half of women with osteoporosis will sustain an osteoporotic fracture, one in two. So statistically that means it’s either gonna be me or it’s gonna be you. In fact, 70% of all hip fractures occur in women.
And for women like Miriam, the minute she breaks her hip, she has a 30% risk of dying in one year from the complications of hip fracture. And she has a 50% chance of never returning to pre-fall function. When I met Miriam in the emergency room, she had simply fallen in her kitchen. She was excruciatingly painful when I met her because fractures are painful. When we were working her up for surgery, we found that she had chronic recurrent UTI.
She had one when she presented and she had never been offered vaginal estrogen and surgery was delayed because her heart was so damaged that she had to be optimized for that.
And that is a very common story. Miriam had a 30% chance of dying for conditions that we know, urinary syndrome of menopause, musculoskeletal syndrome of menopause.
We know they can be prevented with estrogen. Estrogen plays a key role in the remodeling of bone, meaning the balance. There’s a constant balance between breakdown and building of bone.
And when we do not have estrogen, we break down bone at a much higher rate. According to the NIH consensus statement and the European Foundation for osteoporosis and bone disease, estrogen is the only well-established intervention to reduce the frequency of osteoporosis fracture in postmenopausal women to the tune of 30 to 50%. And the WHI itself found a 33% decline in fracture. In fact, the FDA has approved estrogen for the prevention of postmenopausal osteoporosis and yet only 4% of women it is estimated in this country are currently enjoying its benefits. Estrogen is not just a bandaid that we put over the osteoporosis problem when women are very old. In fact, estrogen is critical for the prevention of osteoporosis when women are younger in their perimenopause, in their early menopause,
before we lose 20% of our bone, it’s estimated that estrogen must be used 10 years to change the outcome of fracture. And that once you stop estrogen, according to the least dosed shortest time mantra,
within six years, your bone will rapidly decline as if you’d never had it at all.
From the point of view of this bone surgeon, the data on the benefits of estrogen for prevention and treatment of osteoporosis is undeniable. And I have to admit to you, I am tired of women’s suffering and I am tired of having to put big metal objects for a condition that we could have prevented.
(Thank you so much. – Very good, thank you very much.)
Dr Kelly Casperson:
(Our next presenter is Dr. Kelly Casperson. All right, go ahead.)
If you could click yours off and yours on, there you go. I’m Dr. Kelly Casperson, I have no disclosures.
Your high functioning older sister breaks a hip, as one in six American women will, 30% will die and only half fully recover. But in 2025, a study showed women given a female dose of a safe, inexpensive drug, were 50% less likely to need a cane or a walker six months after a hip fracture.
Wouldn’t you want her to have access to that amazing medication? That medication, testosterone, was first developed in 1935. 90 years later, your sister still can’t get it.
Thank you to the FDA Dr. Marty Makary and Dr. Sara Brenner for allowing me to speak
n behalf of the 108 million American women. I’m a urologist and I care for all genders.
In my clinic, I prescribe testosterone, an FDA approved naturally occurring hormone covered by insurance. But all of those prescriptions, they’re for men.
In fact, one in five men are diagnosed with hypogonadism, a condition where their bodies stop making enough testosterone.
Nearly all women experience the same hormone decline when they live long enough. Men have more than a dozen FDA approved formulations.
But when a woman asks for the same hormone, I have to tell her, there’s no FDA approved dose for you.
The FDA is failing women by denying access to a hormone their bodies naturally produce.
The ovaries and the adrenals make testosterone. Testosterone’s stereotype is that it’s just for libido.
It’s a half truth. It’s a neuro hormone critical for mitochondria,
nerve function, muscle, bone and brain function. Libido improves because dopamine and blood flow in the brain improve. There’s pictures of the brain lighting up some of your work.
Thank you. The FDA has rejected two attempts at female dose testosterone. Not because the products didn’t work, but because they cited insufficient safety data, a legacy of the WHI backlash. But testosterone has been used in women since the 1940s and trans men received 10 times the dose. What other drug do we have where we give people 10 times the dose for 50 years and publish it and then we’re still asking if it’s safe?
Meanwhile, male testosterone products were approved with just six months of safety data.
That is not a lack of evidence. It’s a regulatory and equity failure. With no FDA approved product insurance won’t cover it.
Women are forced to microdose mail products, justify their prescriptions at the pharmacy or pay cash for higher dose, less regulated pellets. Despite these barriers, as many women as men in America take testosterone and I’ve seen what happens when they do,
they start businesses. One said, my math is back. Another, the German I learned as a kid has come back and my favorite, you know that scene from the Wizard of Oz where it goes from black and white to technicolor?
That’s my brain on testosterone. We can’t dismiss this as a lifestyle drug for women who know the secret handshake. Dementia is the fifth leading cause of death in women.
An autopsy study showed that higher brain testosterone correlated with less dementia.
One in four midlife women in America are on antidepressants despite the risk of bone loss and reduced libido.
New data shows more women can come off their SSRIs by adding testosterone then by just using estrogen alone.
Four countries, Australia, New Zealand, South Africa and the UK have government approved female dose testosterone, but only for low sexual desire. That forces women to justify treatment based upon sexual function, an already stigmatized issue that insurance often doesn’t cover.
With this current FDA, America will do better. So here’s what I’m asking.
Fast track female dose testosterone under the new FDA commissioners national priority voucher, it meets all four criteria.
Clarify and simplify regulatory guidance so companies can make cost conscious medications based upon strong established safety data. Approve it for hypogonadism, not low desire.
Work with the DEA to declassify low dose testosterone for women.
The Olympic doping scandals of the 1980s shouldn’t dictate hormone access 2025.
Testosterone is the most abundant gonadal hormone in the body and women deserve access.
The science is solid and the need is undeniable. Picture 108 million women energized, focused and ambitious, not in spite of their age, but because they are supported through it.
That’s the country that we want our children to grow up in. And it’s time for the FDA to act, thank you.
Dr. Makary, FDA commissioner:
– Thank you. Yeah, go ahead. – First of all, thank you for all of these incredible insights, all unique, all different, all talking about a common theme. And that is for too long, women’s health issues
have been sidelined and downplayed and underfunded and underappreciated.
And so that’s why we were passionate about having all of you come and share whatever you think are the important issues related to this topic. Thank you Kelly for pointing out the low dose testosterone. I’m actually gonna be leaving in a few minutes a bit early to meet with the DEA about another matter.
So I will bring that up. I think it’s an incredible perspective Vonda that you bring as a surgeon.
I am amused at the creative ways people are using our one slide rule
to include a lot of information, but I’m learning.
But I did like the octopus Phil, so thank you, very much at my understanding level.
So thank you Sara. Keep going here and I’m gonna be slipping out in a little bit, thank you. – Thank you.
Dr. Mary Jane Minkin:
(Very good, all right, next we’ll go to Dr. Mary Jane Minkin, go ahead please.)
– I’ll put my slide up, first slide. Thank you all very much for inviting us here and this is a great talks.
I’m listening from my colleagues and thank you all for, you know, getting us all together. It’s terrific, I’m Mary Jane Minkin.
I’m an OBGYN, and I hang out in New Haven where I’ve had for many, many years.
I consult for a lot of people. You see them up there. Bear Astellas, Maine, Pfizer, bonafide chaperone brewer.
And my standard line is I consult for them, but they don’t listen to me anyway, so it doesn’t make any difference. So anyway, and I’m gonna put up a slide that is even crazier than everybody else’s, but don’t pay attention to it. Anybody who wants to talk about any of those matters,
grab me after the meeting or send me an email and I’m delighted to talk about them. But I’m gonna focus on two of the issues, which are really my real, I mean, I’m passionate about menopause obviously, but I’m really passionate about a couple of issues within it.
And the first one that I’d like to talk about is education. Because we have a lot of women, we have millions and millions of women out there, and we don’t have enough practitioners to take care of them. And unfortunately we don’t have practitioners who know anything about menopause. And so I’m gonna start talking about the lovely day, July 9th, 2002, that none of us remember, the day that everything, the music died and that all of our patients through their estrogen, as Dr. says, into the toilet, which is why I use regularly. And what happened is not only did our patients stop using estrogen, but the other thing that happened is they stopped learning about estrogen.
Menopause education stopped on July 9th, 2002. And I have proof of this. Okay, the other thing that was going on besides the fact that women were told they were all gonna get breast cancer and die if they continued to use their estrogen therapy, was the fact that they were also, we were in residency programs faced with a dilemma. We were telling our residents they were working too hard.
Now I may debate that, but anyway, but the key thing is that residency hours were being cut.
So they were being cut from 120 hours a week down to 80. So you can’t not train an OBGYN to do a delivery, to do some prenatal care, to do a hysterectomy. Hey, if women are gonna think that estrogen’s gonna make them die, why bother teaching them about menopause? So menopause education got cut too. That died that day also.
And we have proof of that, do I have proof? Yes, I do. And one of the first excellent pieces of proof was published about 10 years after the WHI 2013 when Dr. Wenchen of Johns Hopkins did a nice survey of all the residency programs in the United States and Canada and showed that 20% of them were teaching menopause education. 80% were not, well, we made great strides since then.
And 10 years later, Dr. Peter Schatz and his group, former president of the Menopause Society did a follow-up survey and basically found that now we were up to 30%. Now this is just two years ago, that 30% of the residency programs in the US and Canada were teaching menopause education. So where are these kids gonna learn anything? It’s really tough.
And then what happened is now we’re having an onslaught of women who are now turning menopausal, perimenopausal and menopausal. And when the WHI came out, they weren’t paying attention to the WHI.
They were paying attention to maybe contraception or something else from women’s health, but they weren’t talking about this menopause business.
Well guess what? Now they’re getting hot flashes and now they’re not feeling so good and their brains aren’t working so good and their vaginas aren’t working so good. And they go to their young doctor who doesn’t know anything about this. Uhoh, we got problems.
Now, fortunately there is some good news, okay? And Dr. Surrel and I have participated in running a bunch of courses for these young folks and we’ve had seen marked improvement in people attending these courses wanting to learn something.
But they gotta learn all this stuff. And we also have some good news and that people are turning towards menopause.
And so far as the Menopause Society, which used to run about 2,500 women, 2,500 members per year, actually 2,500 members at all in society, now is up to about 10,000.
Okay, and this dramatic increase has been over the last four years. So there is some hope folks, but we need to start training people and we need to do what we can, whether we need to reach out with the videos or whatever. The other thing that’s crucial is we need to train other practitioners, that we need to train our nurse practitioners. We need to train our PAs and many of them who are tremendously interested in menopause care. And we need to go to them, train them, have them participate in these courses.
Many of our participants in these courses have been PAs, APRNs, who really wanna get involved in the practice.
We need our pharmacist. Everybody needs to get on board and learn. So I think that’s really good that we’re seeing this, but it’s a real dearth of education out there and anything you can do to train these kids, that’s terrific, so keep up that.
Now the next thing I’d like to talk about though is cancer. And that’s my other passion. At about 17 years ago at Yale, we started one of the first sexuality, intimacy and menopause programs for cancer survivors. A very important group out there.
There are over four million breast cancer survivors alone in this country. And we have women who have all sorts of other cancers.
And many of them have gone through menopause from some of the therapies they’re going through, radiation therapy, chemotherapy, surgical therapy.
And many of these women are dealing with menopausal issues. Now, many of these programs do deal with sexuality out there, which is extremely important.
Don’t get me wrong, I’m pro-sex, that’s great. But the key thing is that we need to take care of these women for menopausal issues.
And many of these programs don’t feature that, okay? And so we need to do that. And one of the other important groups out there
are what we call previvers. We are diagnosing many women out there with what we call the genetic abnormalities.
Things like BRCA, BRCA one, BRCA two, and many other abnormalities that basically affect women’s ovarian function.
Okay, by either taking it out, giving them therapies, things like that. And many of the women who know they should have their ovaries out because they’re potentially very dangerous for them to keep in there, are terrified about taking them out because they don’t wanna go through menopause. And unfortunately, many people have been denying them estrogen, not only systemic estrogen, but also vaginal estrogen. And they’re terrified about what’s going on for them. And we know if they keep their ovaries in longer,
they have a higher risk of getting cancer. We have to take care of all these women, all these young women, all these older women.
So I would put a plea up there. And I just wanna end by telling you what happens to my patients. I basically tell every patient whether she has malignancy or question along those lines, or just a Jane Doe average patient when I prescribe her vaginal estrogen, I say, let me tell you what’s in the package insert. Let me tell you about it, et cetera, which is great. They understand it, they go home, and I’ve had this happen to me on many occasions. They put it on the kitchen table, their partner picks it up.
He or she reads the package insert and says, I know what, you know, this is not good.
It says you’re gonna get cancer. It is not worth us having sex for you to get cancer again. So let’s just throw this stuff out.
And they don’t use their vaginal estrogens, and this is tragic. So that’s what I’d like you all to think about, and I’m happy to talk about the rest of the stuff too, thank you all. –
Dr. Sara Brenner:
(Very good, thank you, excellent, all right.
Our next presenter is Dr. Rachel Rubin, go ahead. -)
Dr. Rachel Rubin
Thank you, I have no disclosures.
Good afternoon, and thank you for this life’s honor to advocate for change. Science evolves and must our warning labels.
I’m Dr. Rachel Rubin, I’m a urologist and one of the few fellowship trained in sexual medicine.
It was the persistence of one person during an expert round table that I think changed the world.
In 2014, experts gathered to change an outdated term, vulvovaginal atrophy, used to describe vaginal dryness and painful sex. It was my mentor, Dr. Irwin Goldstein, who helped pioneer Viagra, was the only urologist there. He insisted on adding the word urinary, shifting the focus to the genital urinary system, and making it clear that this was not just a gynecological issue, but a full body health issue. The new term became GSM, Genital Urinary Syndrome of Menopause.
The truth is menopause is a castration event which drastically worsens the health of the genital urinary tissue. And without hormonal support, it never fixes itself.
The genital and urinary tissues are full of estrogen and androgen receptors, like a plant eating water without hormones, we see changes in the microbiome, a loss of acidity and a decimation of the healthy bacteria which translates into symptoms like urinary frequency, urgency, recurrent urinary tract infections, vaginal dryness and pain with sex.
Every day I climb on my soapbox and educate nonstop to patients, clinicians and my social media followers about the genital urinary syndrome of menopause and the magic of local vaginal hormones to cure it.
And holy moly, are vaginal hormones magical. Here’s the secret, local vaginal hormones, estrogen and DHEA are not only similar to, but actually way better than Viagra, because not only do they help with sex and urinary symptoms, they prevent urinary tract infections big time.
This guideline supported fact says that we can prevent more than 50% of people’s urinary tract infections with local vaginal hormones. And we have known this for decades. So why haven’t you heard of this before?
Because your doctor doesn’t know this either. And because my friends, women’s health has a marketing problem.
UTIs, by the way, don’t just mess with the quality of your life. They kill the people you love, a lot of people, and it costs us taxpayers a lot of money. UTIs cost seven million hospital visits a year and make up 25% of infections in older adults. Mortality from UTIs is rising, and we all know that chronic antibiotic use is extremely dangerous.
A 2024 publication by our sexual medicine research team showed that if women in Medicare used vaginal estrogen, which the cash price can be as low as $13 a tube, we could save our government billions of dollars per year in reduced UTI costs. This is why my colleagues and I have spent the last seven years advocating for the American Neurological Association clinical guidelines on GSM, endorsed across multiple specialties, these guidelines clearly state that local vaginal hormones are safe, effective and essential. And yet, FDA, your box label that was blanketly placed on all products in 2003, has no data to support its existence when it comes to these local vaginal hormones. And it scares patients and clinicians daily.
Surely 22 years later, and consensus guidelines later, this deserves another look.
There is not a single study in the literature that says local vaginal estrogen causes stroke, blood clots, heart attacks, breast cancer or probable dementia, which is what your box says.
Not a single study, but FDA, I’m actually here for a personal reason.
Honestly, your label tried to kill my mother. She was in the ICU for six months while in a coma, immunocompromised, and with a catheter. The team refused to start her home dose of local vaginal estrogen. They had never heard of it before, let alone in the ICU setting.
They justified their answer, their no by saying the box says stroke, heart attacks and blood clots.
I rolled up my sleeves and I showed them the data and insisted urosepsis could quickly kill her.
Once they realized I wasn’t backing down, I had the data behind me
and I helped them write the prescription myself. But of course, the pharmacy wouldn’t dispense it because their computer had a big warning alert that came up that said, warning, stroke, blood clots, and heart attacks.
My family and I had to get even louder. When the tube of estrogen finally got to her room, we encountered another hurdle. The nurses had never heard of it and had no idea how to give it.
My family figured it out, but what does everybody else do?
UTIs kill our patients every day. So I’m here to beg you FDA, use the appropriate channels and processes in place to remove that box label. My mom and family deserve better.
All families deserve better, thank you. –
Dr. Makary, FDA commissioner:
Thank you, Dr. Rubin. We’re gonna take a hard look at that.
( Dr. Sara Brenner: Thank you. – Excellent, thank you so much.
All right, our final presenter is Dr. Howard Hodis. Okay, go ahead.)
Dr. Howard Hodis:
– Here’s my disclosures, Dr. Makary, Dr. Brenner, thank you so much for this opportunity to speak to you and our audience. My goal is to present a snapshot delving deeper into the data that support removal of barriers harming women’s health.
Please focus on my slides, the graph in panel one.
Of course, if I show them, it would help. In panel one shows the major outcome data from the WHI E Alone trial. That’s the upper panel and the E plus P trial in the lower panel in these women who were started on HT prior to age 60, as you can see, DVT and the E plus P trial was the only adverse outcome to reach the rare threshold of one event per 1000 women treated per year. That’s the red dashed line.
Other adverse events are below this line are rare and statistically non-significant relative to placebo, including importantly, breast cancer. All cause mortality, all cancer deaths and other mortalities are significantly reduced across both trials.
Colorectal cancer and all cancer types are reduced and contrary to claims, lung cancer is not increased by other either hormone therapy. All fractures and diabetes are reduced in both trials and ovarian cancer is not increased with E plus P as claimed, Alzheimer’s disease
and dementia mortality across all women was significantly reduced with E Alone after 18 year follow up. And with both trials combined, the reduction was significant across both trials.
Panel two shows the WHI breast cancer data. The upper table shows E alone reduced breast cancer and significantly did so in women who were more than 80% adherent.
Breast cancer mortality was importantly significantly reduced by E alone after 20 year follow up.
The lower table shows that in the first E plus P manuscript it led to the media frenzy in 2002, the author stated that breast cancer almost reached nominal statistical significance, meaning it was not statistically significant. Since WHI was not a simple single outcome trial, adjustments were conducted for breast cancer, which was apriori defined as a monitoring and secondary outcome. Included were adjustments for multiple statistical testing, sequential monitoring and confounding bias. Each adjustment also showed a non-significant effect of E plus P on breast cancer. Again, breast cancer mortality was importantly unaffected
by E plus P after 20 years. Note in the last row of the bottom table,
women without prior hormone therapy use before entering the E plus P trial.
That is hormone naive women. That is the women we treat showed a non-significant hazard ratio close to one.
In panel three, the first graph showing hormone naive women breast cancer incidents in the E plus P treatment arm shown by the blue arm, or I’m sorry by the blue line, was not significantly different than breast cancer incidents in the placebo arm shown by the red line.
In the second graph of women with prior hormone use breast cancer incidents, E plus P arm shows a similar incidence as the women in the hormone naive group compared the blue lines. The elevation in the hazard ratio results from the anomalous reduction in the incidents
of breast cancer in the placebo arm of 0.25%.
Compare this with the breast cancer incidents in the placebo arm in the hormone naive women of 0.38%.
This anomaly in the data was further amplified in women who were more than 80% adherent with treatment with placebo rate reduced to 0.15%.
The WHI observational study from 32,000 women, given his degree numbers in the graphs, externally confirmed that the very low breast cancer incidents in the placebo arm anomalously raised the hazard ratio falsely giving the impression that E plus P in the women with prior hormone use was associated with breast cancer. On scientific grounds,
The claim that WHI demonstrates an increased risk of breast cancer is not justified by the published data.
Meta-analyses of other HT randomized controlled trials confirm this conclusion as shown in the green box.
For comparison, table in panel four shows examples of three commonly used medication classes associated with breast cancer with relatives risks two to four times greater than not seen in WHI and are statistically significant.
All medications we use in the practice of medicine have side effects.
Graph in panel four is the Cochrane meta-analysis, which represents data that consistently show HT reduces coronary heart disease 50%
and all cause mortality 30% in women starting HT when less than age 60 or within 10 years of menopause, shown by the green bars. Women greater than age 60 or 10 years beyond menopause when starting HT showed no benefit. This is represented by the red bars.
The Cochrane meta-analysis also showed no effect on stroke in younger postmenopausal women started on hormone therapy.
In summary, the risk benefit profile for HT is excellent, including reduction in all cause mortality and cardiovascular disease, the number one cause of death in women with rare, statistically non-significant risks, including that of breast cancer in the very women started on hormone therapy.
It is past time to stop overstating risks and promoting fear and confusion about hormone therapy, which has been shown to safely offer life enhancing
and life-saving benefits for countless menopausal women, thank you.
–
Dr.Makary, FDA commissioner:
Thank you Dr. Hodis and thank you everybody. We have been here about three months, three, four months. And so we are very eager to take this input and put our heads together
and think about what can we do for women. So you’ve shared what the FDA needs to know, which is what it was the goal of this. I wonder if you would all take a moment to say what you think women in America should know and we can go around briefly. But first I wanna just recognize Dr. Dorothy Fink here.
She is the Deputy Assistant Secretary of Health, and been leading the women’s health office at the Department of Health and Human Services. And if you just stand up real quickly and say hello, Dorothy.
You’re welcome to take my seat when I leave, if you like. Thank you, Dr. Hirsch and Dr. Levy and Dr. Pinkerton and Dr. Manson in absentia.
We were hoping she was gonna be here, but thank you for sharing some of her comments. And thank you Dr. Simon, Dr Surrel, thank you Dr. Diaz Brenton. I want to thank you Dr. Wright as a fellow surgeon.
Thank you, Dr. Casperson, thank you, Dr, it’s Minkin, is that right? Thank you, Dr. Rubin and Dr. Hodis.
You are all giants in this field and we are learners and trying to listen.
So thank you for being here and I will sign off here, but appreciate your input.
Dr. Fink will take my seat here, thank you. –
Thank you, –
(Question from one panelist
Dr. Makary, before you leave,
will you commit to having an open public meeting? )–
Dr. Markary, FDA commissioner:
So we would love to do this all day long, and we would love to go through and have every member of the audience make a comment.
We have a cancer advisory committee meeting. We had lots of stuff this morning, health folks.
So we want input. We want input. And so we are looking to get input on this topic.
The advisory committees are long, expensive, bureaucratic, and they have a long lead time.
But we can, I think, get good public feedback and public comment in other ways.
We’re trying to move faster than the typical government process. And so thank you for being here.
I’m gonna slip out here, but I enjoyed the conversation. Thank you.
Dr. Sara Brenner:
– Thank you so much, Dr. Makary, and a shout out to him for organizing this round table and organizing a whole series of round tables.
Some have already happened, some are yet to come. And his commitment to women’s health as we’ve heard about, and also transparency, which was asked from the audience. So inclusion of ideas, opinions, perspectives, a good hard look at all of the data that exists and a debate around what should be done with those things is really what we’re going for here at the current FDA. So thank you all for that.
We have a few minutes left, 20, or actually, we have a little bit of time before we move to the close, so now it gets fun.
Now we get to ask each other questions. Dr. Fink, do you wanna come up? Yeah, please do.
We coordinate a little pink and purple here on the front panel? Fantastic, welcome.
Do you wanna say a few words about your background and yourself before we open it up for questions amongst the panelists?
Dr. Fink:
– I would love to. So my background is in endocrinology. I did med peds in my training and then during my endocrine fellowship, fell in love with women’s health. And I couldn’t believe the stories of patients that I learned during that time. And I really appreciate the stories that you all shared with us today.
And the women from so many different perspectives, at so many different times of life who experience menopause, who go back to the Women’s Health Initiative and think that they can’t take hormones can be understated. And I also want to mention some things
that haven’t come up today are women that have early menopause. And so women with primary ovarian insufficiency.
And I think some of those stories are the ones that are the ones that really break my heart the most because they’re not just dealing with, you know, the infertility and all the other mental health aspects
of going through menopause in their teenage years, twenties, thirties, forties.
But they’re faced with, do I take hormones, do I not? And seeing the struggles that those women go through and thinking that if they take these hormones, they’re going to get heart disease, breast cancer,
yet I tell them, no, no, if you don’t take these hormones, you will get all of that.
I also appreciated the discussion around testosterone. The number of women who go through early menopause, who have very low testosterone levels is just incredible. And trying to get testosterone for them is impossible.
So thank you for sharing all of this today, and this is such a lifetime opportunity.
And so really thanks to the FDA for bringing all of you together and really giving the chance to change women’s lives.
Dr. Sara Brenner:
– And thank you for letting us put you on the spot. And we didn’t intend to pull you right outta the audience.
–
Dr. Fink:
I love to talk about this. And I’ll just say, so during my endocrine, I’ll finish up by saying, and I became a nationally certified menopause practitioner and my life has never been the same sentence. So yes, but so happy to work with you all.
Dr. Sara Brenner
– Awesome, so I have a whole load, you know, pages of questions, but I’ll only ask one and then see if you wanna ask questions of each other.
This is how you get around your five minute limit for all the things that you didn’t get a cram into the first five minutes, you get another bite at the apple.
But you know, outta all the list of questions. This one that I keep thinking as you’re speaking is I’m a preventive medicine and public health physician, briefly in internal medicine before that. So I love the focus on prevention and upstream thinking.
If you’re a patient out there today, if you’re a woman, okay, what do you ask your physician when you go in?
And which physician do you ask? Is it the primary care physician? Your gynecologist, you might or might not have your urologist based on how you’ve been routed if you ever saw an internist. So for all of the women that are watching today and the men who love the women, who do you ask and what questions do you ask on these topics in a way that they can understand if they’re taking notes? Yeah, let’s help them ask the right questions.
Anyone who wants to jump in, go ahead. –
Dr. Heather Hirsch:
You know, I think that truthfully, all clinicians who take care of women should know about the impacts of menopause, as well as learn about the safety and efficacy of hormone replacement therapy. So I am an internist, there’s lots of gynecologists here, there’s urologists here. But one thing about menopause is true. When you consider perimenopause and you consider the postmenopausal stage, this can be something that lasts for nearly 10, 20 or 30 years.
And so in many ways, internal medicine clinicians, family medicine clinicians are used to looking at chronic health.
And so I do think that while most women maybe start with their gynecologist, we know that studies show that on average, women will go to five to seven clinicians before they get help or support for their symptoms. I do think that the American College
of Graduate Medical Education must place more emphasis on teaching all clinicians and healthcare professionals starting in medical school through their residency training. Because even if a clinician
maybe not going to be the prescriber per se, if there is a clear consensus about who should or could have a consultation for hormone therapy, I do think that that is really, really important. So, so many clinicians should be aware of this.
Internal medicine and family medicine clinicians are acutely aware of chronic diseases, gynecologists and internists can partner together
to help with side effects as well as urologists and even orthopedic surgeons, right?
This spans every single specialty in my mind, except for pediatrics, except for the patients that have premature ovarian insufficiency, right?
So really, everybody needs to know this. And I do wanna make one more point. You know, I do believe that none of us here believe
that hormone therapy is absolutely appropriate for every woman. But we do believe that the unnecessary fears mean that there’s lack of clinicians who understand it. And it’s scaring women to consider taking it.
But women should know all of their options.
–
Dr. Barbara Levy:
And I will say though, that the reality is, most of the time when women go in with a list of questions and all the right things, they’re dismissed. Or a blood test is done and we haven’t even addressed the issue of trying to draw a blood test to make a diagnosis. The hormone levels vary every 90 minutes or so.
So you get a single moment in time. But the reality is that women have to be self-sufficient.
They have to understand things. Looking for a menopause society certified practitioner is a help if you can find one. But it’s a challenge.
It is a challenge right now to find a physician or a practitioner who has the expertise and who will listen, who will understand that you know more about your body than I do.
And that if you’re suffering symptoms, even though you’re still having periods, that’s the perimenopause that we didn’t even get into today.
But those women are dismissed and they’re told, oh, your hormone level’s normal, so you can’t be having symptoms, that’s just not true. –
Dr. Roberto Diaz Brinton:
I’d like to jump in here from the brain side
and talk about the symptom that women approach physicians
for most frequently, and that’s the menopausal hot flash. And I mentioned in my talk
that the hot flash is actually being, the heat is actually being generated in the brain, right?
And that’s why the hot flash, I know the vasodilation, occurs from here to here.
It’s releasing brain heat and where’s that heat coming from? It largely is coming from an neuro immune response that’s happening in the brain where the white matter is actually being recognized
as a foreign invader and being engulfed by the neuro immune cells.
And that strategy of, you know, kind of destroying this foreign invader
is actually to free radical it to death, just like the neutrophils do in the periphery. And that is a major heat generator.
And so that’s in part why these episodes of hot flashes are episodic.
What I will also say is that having conducted clinical trials in women specifically for hot flashes and addressing their concerns around the hot flash is I am absolutely shocked and both amazed at what women will endure. That the hot flash appears to be somewhat benign
unless you’re experiencing it at work, unless you’re experiencing it multiple times at night.
It’s called, you know, night sweats where you’re literally feel like you’re burning in the heat.
So this is, you know, a common symptom of the hot, or of the menopausal transition.
It is not an innocuous, it is not, you know, without a consequence, so.
Dr. Sara Brenner:
– Okay, very good. We had one comment over here, and then we can go over here. –
Dr. JoAnn Pinkerton:
I direct a very large menopause clinic.
And so I see women who come in every day who say, I wasn’t listened to, nobody talked to me about hormones, I had hot flushes, I had sweats, I had brain fog, or I’ve got osteoporosis.
Why didn’t somebody talk to me about hormones 10 years ago? So many women suffering and now it’s menopause is being commercialized and now there’s so much information out that isn’t evidence-based. And so what I tell women is you want to follow the science, you want to find somebody who is a credentialed practitioner who is going to give you the dose that works for you, that’s gonna listen to your issues and your health issues and then work with you. And so often people are finding people who are putting in super high doses pellets, things that are not FDA approved when we have FDA approved safe therapies.
And so I just tell women, if you’re not getting the care, if you’re being just told that it’s in your head or just something to tough out, find a menopause credentialed practitioner. You can find them on the zip code for the Menopause Society.
There are a lot of women doctors, men doctors who care about you as you go through menopause.
And there is nothing more gratifying than helping somebody’s hot flushes get better, but also preventing their fractures and helping them navigate their work issues when they get brain fog. So if you’re suffering, ask for help and stop this fear.
Dr. Kelly Casperson:
– Okay, I wanna give some take home tips for people at home who, to answer your question of how do you navigate this?
People wrongly assume that gynecologists should take care of 50% of the American people. The numbers don’t make sense.
There’s 80 million women over the age of 40 and we’ve got about 48,000 gynecologists. We need all hands on board, which is why we’re so diversely represented here with internal medicine and surgeons and urologists who have to do their own study ’cause you can’t just go to a urologist and get this, so ask the clinic before you make the appointment.
Don’t pay for parking, don’t take a day off of work. Say, do they deal with women in menopause and specifically treat hormones if that’s what you want.
So don’t find out once you’re already in the clinic. That’s my first tip, my second tip is once you’re in the clinic, say,
I know there’s a lot of new science and data coming around about hormones, I’m wondering if we can try X,
whether that’s vaginal estrogen, whether that’s a low dose patch. You say, I wonder if we can try X, I promise to follow up in three months
and we will change the dose and adjust as needed. Doctors love follow up. So you feed them that line and they were like, that’s how you partner, right? We’re gonna try something but we’re gonna see how it goes and we’re gonna adjust as needed. And I found that to be very helpful. Take home tips for people to say, how do you talk to doctors to try some of this?
Dr. Mary Jane Minkin:
– Excellent, one of the problems unfortunately is all of this takes time and menopause is an extremely time consuming, it’s extraordinarily fulfilling. And JoAnn’s right, there’s absolutely nothing better when you can take care of somebody’s hot flashes and get her back to a normal life. I mean it’s thrilling and it’s great and you’re doing,
and I think it was Wonder Bread, good and good for you was the advertisement, I think. And that’s sort of what I view with estrogen, good and good for you.
But the key thing is it takes time. And unfortunately people need to have, you know, they need to get reimbursement for the care.
And we also, and I’ll just put another plug in here for one of my favorite topics or prior authorizations, that medications, many of these things that we prescribe do require prior authorizations. So if you all in the FDA can do anything about taking care of that, that’d be just fabulous. But these are the kind of problems we encounter
as practitioners. – Okay, thank you, go ahead.
–
Dr. James Simon:
[Speaker 2] Oh, I had a question for Dr. Levy. – Oh, go ahead. – [Speaker 2] Is that okay? – Fire away. – You mentioned in your discussion,
[Speaker 3] Dr. Barbara Levy
Sure.
– From the box warning to. – Yeah, so the beers criteria is the list of medications that the American Geriatric Society creates every couple of years.
The National Center for Quality Assurance and CQA that certifies health plans creates a set of quality measures against which they measure health plans.
The Beers criteria, that list of potentially hazardous drugs in the elderly is one of the criteria that’s used. So because health plans get dinged if they have a lot of older women on hormone therapy, they create barriers and the barriers might be tiered pricing so that it’s so expensive to, even though it’s covered, it’s covered at a level that makes it almost impossible for people to be able to pay for it.
And that’s my point about initiating hormone therapy is different than continuation of hormone therapy.
And that is a barrier that is just really difficult because that financial barrier for people is very challenging. –
Dr. JoAnn Pinkerson:
I also just have to say, I just love it
when you have somebody with vaginal atrophy or recurrent UTIs and you wanna give them a low dose local therapy and it’s, you know, maybe an estrogen cream and you get back, must try an oral systemic hormone therapy or a vaginal ring dose for a vasomotor symptoms, which is systemic. I’m like, where is the science?
Why can’t we clarify that local vaginal estrogen is local?
Dr. Sara Brenner:
– That’s an excellent point. And I was thinking as folks were talking, what are the major data gaps that you see?
You’re very well versed in the literature. Most of you are practicing, what studies have yet to be done, what evidence are we lacking and how could that information help inform both physicians and patients, but also FDA and other federal colleagues?
Dr. James Simon
– So I’d like to pose the exact same question in a different way. –
(Please do, go ahead.)
– I think there’s lots of literature and lots of data and each of us could go around and find the study that we’d like to have done.
Yeah, I’d like to see the FDA follow the data.
Dr. Barbara Levy:
– So I would like to say that nobody’s gonna fund another large randomized clinical trial.
And so what we have to do is get bigger thinking and combine data from RCTs, from Cochrane, with real world data. There’s a lot of real world data out there.
And I think the hugest gap in my experience is perimenopause. It really is, we understand quite a bit about menopausal hormone therapy, about the trajectory of what happens beyond 12 months without a period.
We don’t understand a lot. We have this study of women’s health across the nation that kind of gives us a population level, but how should we treat a 43-year-old with vasomotor symptoms who’s got morbid obesity, she’s got risk factors for endometrial cancer, she’s got risk factors for heart disease.
As a clinician, it’s very difficult to have any data really to support that.
There’s a lot of clinical input that, you know, my 42 years of experience can help.
But it’s very challenging because that perimenopausal seven to 10 years is a long time and there’s a lot of change happening over that time.
Dr. JoAnn Pinkerton:
– I just wanted before you jump in, what we don’t have is what we are doing clinically, we believe that if we take women who are initiating at the right time between 50 and 60, you know, within 10 years of menopause onset, and we give them transdermal estrogen and micronized progesterone, we believe that there is no increased risk of heart events and no increased risk of breast cancer.
And we may actually be preventing heart disease, but we don’t have that data because the WHI was with conjugated equine estrogen
and oral product and a synthetic progestin. So we would love data to tell us that what we’re actually doing is safe because we believe it based on all of the data that’s out there. We just don’t have good randomized clinical trial data for that. –
Dr. Kelly Casperson:
Okay, yeah. So what I would kind of dovetail on what you were speaking about earlier and why I focused on hot flashes is that the principal reason why women seek intervention is for the menopausal hot flash. And what our data show is that even before there are these hot flashes, the brain is changing. And it’s this silent dismantling of this estrogenic system that is being driven by the immune system.
And that so oftentimes women will experience, you know, multiple immune abnormalities as they transition.
And that it’s really body wide. We’ve been studying from the neck up, but you know, for many women they will develop, beginning to develop multiple autoimmune conditions. The second point that I think is critical is I know, what do women do when they have elected not to receive hormone therapy for the fear of breast cancer. And that’s the principle reason. And to what extent we can change that perspective, we are developing a strategy that, you know, targets brain health while also protecting breast health because 80% of women elect not to receive hormone therapy for the fear of breast cancer. And that they’re really sacrificing up their brain as well as other organs. They think breast cancer is going to kill me, I’ll take my chances on Alzheimer’s,
Parkinson’s, MS and ALS.
Dr. Sara Brenner:
– Did we have other other comments? –
[Speaker] That’s an interesting feature.
–
–
Dr. Sara Brenner:
I’d like to make a comment. –
[Speaker] I’ve never known that you could double tap and then after all of these, well maybe there’s an actual glitch. In any event, if your mic is on, go ahead.
Dr. Vonda Wright:
– Could I go ahead? –
(Go ahead and then go too down, go ahead.) –
Although I am a whole person doctor, I wanna stay in my lane and I don’t want to fail to recognize that as we talk about all these other things, there are estrogen bean receptors on every tissue of the musculoskeletal system bone we talked about today.
Muscle, tendon, ligament, annulus in the spine, adipose tissue, cartilage, the cost of musculoskeletal this country that could be prevented by addressing estrogen early in the perimenopause
to prevent something that’s known for 30 years we’ve known about the arthritis of menopause.
It’s been published and yet for many, many reasons and we’re talking about what research needs to be done, for many, many reasons, it’s completely under-researched and under-addressed and under prescribed.
And orthopedic surgeons don’t know about it to notice that when their bone is like butter, that’s because they haven’t had their estrogen. When your implants will not stay in, it’s because they have not had their estrogen.
So if we’re talking about where can we do more research, I love the conversation to remove the hesitancy from the labels or whatever has to be, because we will get studies through the IRB more easily.
So simple surgeons like orthopedic surgeons can do the studies that will take care of women with the musculoskeletal syndrome of menopause, which affects more than 80% of all women at the rate
of night sweats, brain fog and hot flashes.
Dr. Sara Brenner:
– Very good, I think an issue might be when multiple mics are on. So if you’re not speaking, mics off.
Okay, and then. –
Dr. Mary Jane Minkin:
One issue that might be more, even cheaper, It into cheap is, if we can get some consistency from certain governmental agencies to be consistent. And I’m gonna dump on the USPFTF whatever task force stuff because we have spent a lot of time because what comes across is, you know, I mean I say to my patients, and I’m a bad girl, you know, I come across and I say, well I can tell you estrogen officially prevents osteoporosis.
That’s cool. I can talk to you about that, but I’m not allowed to tell you that estrogen protects against the hearts. ’cause the USPF, whatever task force says,it doesn’t prevent heart disease. And if we could get some consistency with some of the governmental organizations, that might be something good that we wouldn’t have to try to, you know, convince our patients. And then what happens is some of the internal medicine people, no offense to the internists, but what happens is that they’ll come out and say, well, the USPF task force says it doesn’t prevent heart disease. So trying to kill you by giving estrogen therapy, which happens regularly in our town. So if we could get some consistency, I think that would be helpful.
–
Dr. Barbara Levy:
So I think that is such a great point. The US Preventative Services task force is made up of methodologists and this is a panel of clinicians and there’s a distinct difference.
So when they publish their guidelines, the gold standard is the randomized clinical trial.
So when you look at the reference list, everything hearkens back to the Women’s Health Initiativeto conjugated equine estrogen and medroxyprogesterone acetate in women over 63 years old.
And that’s a real problem because that is not the therapy we’re talking about here today.
It’s not clinically relevant. But when you’re a methodologist
and you do evidence-based medicine, that’s what you use.
And so the makeup of the US Preventative Services task force is an issue.
Dr. James Simon:
– So I’d like to follow up on Dr. Wright’s comment about musculoskeletal system and our task here today about hormones
by suggesting that avenue of investigation, which was your initial question, include a greater understanding of skeletal and musculoskeletal loss with aging. What we commonly refer to incorrectly, in my opinion, is sarcopenia and frailty. This is a huge cost to all of us and very poorly understood.
And I would like to see some emphasis maybe from FDA, NIH et cetera in putting some money behind investigating ways, including possible hormone treatments, maybe androgens, to reduce and prevent sarcopenia and frailty in both aging women and aging men.
Dr. Kelly Casperson:
– Thank you for that. – [Speaker 3] Can I do one more? – Yeah, go ahead. – Okay, thank you, give us an FDA approved female dose testosterone so we can actually do research on a standardized product. And when we have that, the beginning story I did about that woman who was able to walk without a cane or a walker at six months while taking testosterone, why is that, increased trunk muscle strength, increased core strength is why she did it in that study published in JAMA 2025.
And I agree and I would tie in, studies on our frail individuals, it is costly, they’re going into nursing homes.
How can we keep them from losing their freedom, by keeping them vital, by supporting all of their body parts that hormones help. And that would include testosterone, especially in the frail at depopulation.
Dr. Sara Brenner:
– Okay, excellent. – [Speaker 4] Can I pose a question? – Go ahead. –
Dr. Heather Hersh:
I would like to ask this to either Dr. Hodis or Dr. Simon or Dr. Pinkerton. You know, in my opening statement, I said that history got it wrong and I saw your pin.
I love the WHI and I do too. The WHI is a fantastic study.
It actually is the study that has the most safety data about hormone therapy.
And so my question for some of the experts on the panel here is what is this discrepancy between the WHI and some of the fears that we still have around menopausal hormone therapy? If it is indeed the box label warning, but can we talk a little bit about that? –
Dr. Howard Hodis:
Well, let me say a few words.
There’s a lot to say about that. Some of it not appropriate for this audience.
I showed you some of the data as I delve deeper into it, it’s not as simple. You give the drug and you get cancer, which appears not to be even the case with WHI.
And as you look at the data carefully, we see no matter how large a trial, there’s always issues.
And we see that in the data, IE the graphs I showed, there is no evidence within those graphs that there’s any increased risk of breast cancer. Further, there’s issues that have been published in the literature. And I think this is why Dr. Simon is correct, we have 50 years of data. These data should be followed and not just the data that that we see that give us these, you know, particular outcomes that we wanna believe, but look at all the data. So there’s been publications that have said that in WHI lung cancer has increased, it’s false, ovarian cancer has increased statistically now it’s false.
And this gets into the press and it’s not the press’s fault. This gets into the press and this gets fed into our society, gets fed into people’s minds, women’s minds and their husbands or whoever. And this hurts the true data behind hormone therapy.
It feeds negative data. Another example I’ll give, which really hit the press big time, was the claim that when WHI was published and we know that hormone therapy dropped by about 80% in this country, that the incidence of breast cancer in this country dropped.
Now that was a statistical change in how the data was being analyzed
by the group from the CDC who determines the epidemiology of cancer in this country.
So we see a minimal decrease from 2002 to 2003, but every year after that, breast cancer has risen in number and incidents in this country year after year.
So it did not decrease. But that publication in New England Journal still sitting out there and authors are still making the claim that it reduces breast cancer.
And we just saw something, I don’t know a few months ago that was told to me in the New York Times, claiming how many women’s breasts have been saved and how many lives have been saved.
But the data are opposite to that. But that’s what women are seeing and reading further, I just wanna say this, after 50 years of looking at breast cancer and as hormones being a cause of breast cancer,
we still do not have an answer. I just need you to think about that 50 years at least 40 observational case control studies, randomized control studies, billions of dollars spent.
And we still don’t know whether hormones cause breast cancer.
My thought is if the signal is there, we certainly would’ve seen it by now and it would’ve been a consistent data showing a breast cancer. So I think we just need to think about all this logically. We need to look at the data, both the true data as well as the false data.
–
Dr, JoAnn Pinkerton:
I just wanna interject just a little bit of caution that when we are thinking about all of these therapies, that there are some things that are individual based so that people at higher risk need to be thinking about this, longer dose, higher dosages, people who are using it in their 70s and 80s, that we don’t really know exactly what happens with estrogen in the breast.
And what we do know is that in older women, when we started in the WHI conjugated estrogen and MPA, we did see more heart events and more strokes. So we have to be very thoughtful about how we give this data so that we can help women take hormones safely when they need them and feel comfortable that we’re doing it without scaring them that they’re automatically gonna get breast cancer. So I would say it’s not proven, but I do have to say, you have to put a little caution out there. –
Dr. Howard Hodis:
[Speaker 4] I have no problem with caution. – Okay.
– But you gotta discern in prevention-ology between initiation and continuation.
We don’t start, I hope, people on blood pressure medication
and five years later, 10 years later, 20 years later say, oh, your pressure’s great. I’m gonna take you off that medication, ’cause the first thing that’s gonna happen is they’re probably gonna stroke. And we know in fact there are data, good data to finish
epidemiological the nationwide study that women who stopped their hormone therapy, now this is a country that has probably the best database for mortality in the world.
And what they reported was in the first year of removing hormone therapy, the women stopped because of fear. ‘Cause remember, WHI went internationally, 150% increased in acute myocardial infarction,
130% increase in stroke. And Dr. Makary noted about a 25% increase
over the entire following years. And we know bone does the same thing.
You stop hormone therapy, you lose bone and you will fracture. So there’s a complete difference between initiation and continuation. And I think as we think about therapies and every therapy we use statins, has your doctor taken off a statin when you’re healthy and said, oh, you’re fine now ’cause your cholesterol’s below 100, I would hope not ’cause you better start looking for a lawyer. So the bottom line is we gotta be cognizant of this and the language we use. I agree with you JoAnn, caution always because we don’t have firm answers
to some of these vital questions. Now, do they deserve a box warning?
That’s not for me to decide. That’s the FDA and all I’m doing is presenting the data in the best way I can.
But clearly when this misinformation and this confusion and this idea of somehow making the lines fuzzy around starting and continuation, which several people do in this field, is not helping women.
We need clarity and we need guidance and we need to continue the safety obviously.
But in addition, I just showed one slide of three classes of drugs that increase breast cancer.
If you don’t take hormone therapy and you end up on SSRI because you’re depressed or you wanna get rid of brain fog or deal with your menopausal symptoms and you end up on a bisphosphate and you end up on all these drugs that one drug can do, these drugs are gonna cause atrial fibrillation.
They’re gonna cause bone fracture, a potential stroke risk with some of these drugs.
You’re adding on one potential risk to another from three, four, five drugs that these women require to feel good, which they never feel as good when they’re on hormone therapy that have all really similar risk than just hormone therapy alone. And that’s my point of saying this one drug has an excellent risk benefit profile. And I can and you can challenge me on this and I can present you with the literature to show all these risks undoubtedly.
Dr. Sara Brenner:
– This is so fantastic. I know we have so much more to cover. We have one minute left. I’d like the full semester course from each of you, can we offer that? So this has just been great. I’d like to turn it to Dr. Fink
to say a few words and then we’ll close out for today. –
Dr. Fink:
Well, thank you all. There’s just an incredible energy emanating from this discussion. And you know, when you think about for all the women out there listening, whether you’re presenting to your primary care doctor, your OBGYN, your urologist, your orthopedic surgeon, I mean, what an incredible group of people here today to really be thinking. You know, like if you have a symptom and you’re not getting answers, there’s so much hope out there. And keep trying to connect those dots and help to connect those dots for friends and family.
And we really look forward to continuing to engage with all of you and taking next steps to really change women’s health. –
Dr. Sara Brenner:
Thank you so much Dr. Fink. I know there’s so much more to say.
I’d like to let folks know that we do plan to open a public comment period on this topic through the federal registrar and we’ll do that as quickly as we can, hopefully as early as next week.
So I’d like to thank all of our panelists for taking time outta very busy schedules, including seeing if patients to join us here today in White Oak. And for the audience who joined us in person and for everyone who’s listening online, both now and later, we are very grateful for the expertise, insights and also anecdotes from your treating patients that we saw today as well as your personal reflections.
Your thoughtful contributions help shed light on our current state of scientific knowledge about the benefit and risks of hormone replacement therapy and other medications. Thank you for your engagement and interest. As we know, this topic affects and impacts millions of women now and into the future. And your participation is a reminder that transparency and collaboration are essential to building trust and making progress. We look forward to continuing the conversation in the days ahead, and including the opportunity that I just mentioned. And I’d also like to just throw in that I love
thinking broadly about all of these topics, but also hearing, and several folks mentioned about a personalized medicine approach
where individual patients can consult with their physicians about how to interpret broad recommendations, including those that may have benefits and risks and tailor them down to the individual person at that point in their life.
So thank you again very much, and also to our crew for making this possible. Have a good day.
– Thank you.
******Note from this Website Editor :
Attempt to understand this sentence from Dr. Phillip Sarrel, asked AI assistance with WHI findings.
Copilot said:
…“So if Dr. Sarrel’s statement was specifically:– There was a decrease in estrogen use and a decrease in deaths from dementia according to WHI—,
that would not fit with my understanding of the WHI findings.”…
….”Personally, if I were reviewing this as a scientific statement, I would be cautious. The parts about lower all-cause mortality, cardiovascular disease, breast cancer, and hip fracture in the younger estrogen-only subgroup are consistent with published WHI follow-up analyses.
The specific claim about a decrease in deaths from dementia is the part that immediately raises a question for me, because it is not one of the commonly cited WHI findings, and the better-known WHI dementia results in older women pointed in the opposite direction.”….
PurenHealthInfo.com 