Welcome back to another episode of MedCity FemFwd, a podcast dedicated to exploring the breakthroughs and challenges in women’s health. In this episode, we’re joined by Janna Manjelievskaia, director of health economics and outcomes research at Veradigm.
We discuss Veradigm’s recent Women’s Health Insights Report, which highlights the complicated history around Hormone Replacement Therapy (HRT), a medication used to treat menopause. The report shows how rates of HRT fell after a study by the Women’s Health Initiative found that HRT is dangerous. However, this study has since been debunked, and HRT use is back on the rise.
Here is an AI-generated transcript of the episode:
Marissa Plescia: Welcome back to MedCity FemFwd. I’m Marissa Plescia, reporter for MedCity News. In this episode, we’re joined by Janna Manjelievskaia of Veradigm to discuss the company’s recent Women’s Health Report, which has some interesting findings on hormone replacement therapy. But first, we have a message from Veradigm
Marissa Plescia: Hi, Janna. Thanks so much for joining MedCity Fem Forward. Thanks for having me. Yeah, of course. Maybe just to start, can you just tell us a little bit about yourself and what brought you to Veradigm?
Janna Manjelievskaia: Yeah. Um, well, I, I’ve always been somebody that asks a lot of questions. Um, so it was, it was sort of a natural path for me to pursue, you know, research degrees that would allow me to ask questions for a living.
Uh, so I’ve, I’ve been a health services researcher for most of my career. My background is in health policy and epidemiology. But I would say that, you know, what drives a lot of my work is just a genuine curiosity in trying to answer difficult research questions. Um, at Veradigm, I lead a team of researchers where we use data from electronic health records to conduct, uh, studies across really a wide range of therapeutic areas.
Veradigm, um, at its core is a health technology company. Um, but my team in real world evidence uses the EHR data that are generated from providers and practices within the Veradigm network to conduct our studies. So these are all protocol-driven research studies that typically result in a peer-reviewed publication or a conference presentation.
Um, I’m obviously biased, but I think, you know, we have some of the best researchers in RWE space. It’s, it’s a super crowded market. You know, everybody wants to tell you about their latest AI-enabled capability. Um, to me, it always comes back to having a methodologically sound approach to answering a research question.
So in, in observational research, which represents kind of a significant portion of what we call real world evidence, there are, you know, tons of limitations. So you have to really carefully consider how you’re going to design your study to be able to meet your study objectives while accounting for those limitations.
At the same time, um, real world data play a really important role. So if you, if you can picture, like, the evidence-based research pyramid that, um, you know, ranks the quality of evidence, observational studies tend to be at the bottom. Um, and definitely below experimental studies like, you know, randomized or even non-randomized clinical trials.
However, um, we’ve seen a, a significant and a positive shift in how real world data are perceived by the FDA, um, where now they can, you know, they can help inform regulatory decisions. Additionally, real world data can help fill really crucial gaps in research where clinical trials simply fall short, or maybe it’s additional evidence following the completion of a trial.
So, you know, it may not always be ethical to do a traditional trial. Um, it’s often time consuming, really costly. It’s hard to achieve true representation in clinical trials, and that’s where I think that real world data really shine.
Marissa Plescia: Yeah, absolutely. Thank you so much for sharing that And going off of that, you recently, um, released the twenty twenty-six Women’s Health Report.
Why did you decide to conduct this report?
Janna Manjelievskaia: Yeah. So I mean, women’s health has long been a research interest for me. Um, I mean, I, I find it funny to even say women’s health like it’s some niche research topic and not, you know, over half the US population. But un-unfortunately, if, if we look at women’s health as a distinct research field, the amount of data available and the funding allocated would suggest that it is very much a niche field still to this day.
Um, you know, funding for women’s health has continued to decline over the past decade. Um, you know, less than eight percent of the overall NIH budget is dedicated to women’s health research, and I mean, this, this shows, you know, that the US has the highest maternal mortality rate of any other developed nation.
That’s quite frankly embarrassing. Um, and it’s been like this for decades, you know, since before I even started studying any of this, um, studying health policy in college. But I think the bigger point is that it’s, it’s only been thirty-three years since women were required to be included in federally funded clinical trials.
So that’s, that’s in my lifetime. You know, uh, up until that time, you know, women’s health was really confined to only existing inside an OBGYN clinic. So when a, a lot of the drugs that we commonly use today, they were being developed, they were tested primarily in men, and it’s really difficult to extrapolate those findings at a population level when over half of that population never even had a seat at the table.
Um, and there are t-tons of examples where, you know, women really suffered from this as a result. So anyway, as I, as I progressed through my career and I, I started studying the literature about, you know, female specific conditions and my own experience with the healthcare system, I, I was just met with, you know, a lack of data in one regard, and then met with criticism from the healthcare system for asking difficult questions about, about my own care.
Um, I mean, why, why did it take me nearly two decades of seeing different providers to get a correct PCOS diagnosis, one of the most common conditions among women of reproductive age? Um, and the standard of care is, you know, just now catching up to the literature and the fact that, you know, there’s different phenotypes of this condition that exist.
Um, you know, not every patient is going to look the same or, you know, exhibit sort of the classical symptoms that we think about. And then, you know, the treatment options for most women with PCOS in this country are still very much dependent on whether or not you’d like to get pregnant. Um, so that’s, that’s what the provider will ask you, and if your answer is no, you, you get put on an oral contraceptive, um, to regulate your cycle and kinda be sent on your way.
You know, zero regard to your fasting insulin, to your hormone levels, anything that concerns your metabolic health And we saw this in our own data in this report when we looked at the PCOS cohort. You know, the labs that were done when they were done, and that’s, that’s, you know, pretty rare. It’s, it was never a full workup.
Um, so there’s just, there’s a serious issue of delayed diagnosis and misdiagnosis, and I think we, we have a long way to go there. Um, but just to pivot from that to, you know, talk about hormone replacement therapy, because that’s an important topic we cover in this report. And I chose to focus on the peri- and post-menopausal years as a key component of this report because that’s a really important time in a woman’s life.
Um, not that adolescence or reproductive years aren’t, and they certainly bring their own complexities. But this point of midlife and later life is when a lot of women are really at their peak. They’re at their peak professionally, um, you know, usually financially. They’re, they’re often the primary decision-makers for healthcare, um, for their spouses, their kids, you know, even their parents.
And yet, their bodies are starting to undergo this profound change. And so this is a time when a lot of women will actually leave the workforce, either temporarily or permanently. Um, so it, it goes beyond just being a health issue and it turns into an economic one. And, you know, the interesting thing that I, I always say and I, I hear other people say also is that, like, no one medical specialty really owns menopause.
Um, and let’s get one other thing out there too, like, menopause is just a day, right? It’s, it’s usually determined retroactively, and then you go back in time and say, “Okay, maybe this is when I went into perimenopause,” and it, you know, aligned with the symptoms I had at the time that maybe I was confusing for something else.
So I, I’m just fascinated by the hormonal changes that happen during this period of a woman’s life. Um, it’s something that all of us will go through, you know, assuming we live long enough. So when you ask why we wrote this report, it’s, it’s really just our way of trying to fill, like, a tiny portion of the huge gap that exists in women’s health research.
Um, and just to end this question, you know, studying women’s health is by no means somehow minimizing the importance of men’s health issues. In fact, I think it can only benefit both sexes. Um, I mean, the leading cause of death in the US is the same for both men and women, which is heart disease. Um, we may not always look at it through that lens, but so, you know, our team at Veridigm, we have access to data on millions of patients.
And so I thought it was important to start our foray into women’s health by first painting the landscape of where things currently stand, and that’s, that’s what you’ll find in this report.
Marissa Plescia: Yeah, and going off of that, the report talks about the complicated history behind hormone replacement therapy. Can you talk a bit about why there’s a complicated history?
Janna Manjelievskaia: So it’s… Well, how much time do you have? But it’s, recently, you know, recently there’s been a lot of attention to the findings from this one study called the Women’s Health Initiative or the WHI.
Um, you know, this was a study, it was announced in the early ’90s, and I believe to date is still the largest women’s health clinical trial ever conducted, um, at least in this country for sure. But I guess let’s talk about why it was conducted in the first place, which was truly remarkable. It, it was backed by over $600 million in NIH funding, and it was meant to sort of make up for all the lost time in which women were excluded from research.
So they ended up enrolling over 160,000 women in the US, um, all post-menopausal. And they, they wanted to study areas where they had significant gaps in women’s health research, which was primarily chronic conditions like heart disease, uh, cancer, osteoporosis, dementia, um, but also things like blood clots, and this was all how it related to receipt of HRT.
Now, prior to the WHI, there were already a number of observational studies, uh, in the late ’80s, early ’90s, um, that showed that compared to women who were not treated with hormone therapy, those that were treated tended to have lower rates of heart disease, um, lower all-cause mortality, less cognitive decline, so, like, all great things.
Um, so H- HRT prescribing was not a new thing. Providers were already widely using it aside from just the typical menopausal symptoms that we think about, but they were using it to prevent heart disease and these other kinda long-term chronic conditions. So they needed a clinical trial to confirm these findings.
Um, so what they did was, you know, they randomized these women to either receive a combination of conjugated equine estrogens and MPA, it’s medroxyprogesterone acetate, which is essentially just an estrogen/progestin combo. This is for the group that had a uterus. If they didn’t have a, a uterus, they just received the estrogen, um, or a placebo.
And the reason I was, like, focusing on those names so much is because that’s, that’s not what’s used anymore. Um, this was a birth control style pill of synthetic estrogen and progestin, not the FDA-approved HRT products we use today. So, you know, they just examined one dose of one medication, and that’s, that’s really important to note because that’s, that’s a huge limitation of this study And so I’m, I’m kinda skipping a lot here, but they, they eventually had to stop the study early because they said that HRT, you know, that group, they– it was– they had an increased risk of breast cancer, risk of blood clots, and cardiovascular disease.
Um, now this was 2002, and they did something very bizarre, I thought. They, they held a press conference to announce that they were stopping the study, and the press conference actually preceded the publication from the study, which is also really wild to think about and it’s, like, not common practice. And it seemed like almost overnight prescribing for HRT just plummeted.
So there’s some estimates that say, you know, at that time around 40% of eligible women were on HRT, and after that press conference, it was reduced to, like, 5%. So this amount of attention may have been warranted if the data were interpreted correctly. Um, and that’s, that’s how we get to where we are today, where we have an entire generation of physicians who were never taught how to prescribe HRT, um, generations of women who were taught to be afraid of it.
And I mean, like, let’s just call it what it is, it’s fear-based medicine. Um, but I, I wanna go back and just focus on the actual findings and how they were inter- uh, interpreted versus what the data showed. So the main finding that got all of the attention was the women that were in the synthetic progestin/estrogen group, this is the group that had a uterus, they had an increase in the incidence of breast cancer, but there, there was no effect on mortality.
Now, they reported the relative risk for this group, which was a 24% increase in incidence of breast cancer. So that 24%, you know, that, that’s a number that sounds really scary when you say it out loud. Um, what was completely ignored was the absolute risk. Now, if you’re not a researcher or, you know, if you don’t read these types of studies, that, that probably doesn’t mean much to you.
But you see the NIH getting up there and doing a press conference to announce that they’re ending this massive trial that everyone was so excited about because of breast cancer risk, and that’s, that’s probably enough to scare away the average person from ever looking at HRT again, which that’s exactly what happened.
And the absolute risk increase was 0.1%. To me, that is such an egregious misinterpretation of the data. Um, so why is there a complicated history to HRT? Um, well, I, I just listened to a really great talk between two leading physicians in this field, um, Dr. Rachel Rubin and Dr. Kelly Casperson, and they said that, you know, the real danger to women isn’t HRT, it’s bad science
Marissa Plescia: Yeah, very interesting right there.
Thank you for sharing that. Um, and what did the report find about how HRT use is changing?
Janna Manjelievskaia: Yeah. So, um, before we published our report, there, there was a study published in JAMA in, um, 2024 that looked at trends in HRT using NHANES data from 1999 to 2020. So their study ended just pre-COVID. Um, and they found that by 2020, HRT use had declined to less than 5%, and the greatest decline came from women, um, aged fifty-two to sixty-four.
And they, they observed this decline across all racial and ethnic groups. Um, of course, not surprisingly, women in minority groups had even lower prevalence of HRT use. So in, in our report, we were able to use, um, newer data through the end of 2024 and account for the pre-COVID years, during and post-COVID.
Um, and we looked at all data from 2017, uh, through 2024. This is a really big sample size, um, nationally representative data, and I believe for each year of the analysis, we had anywhere from five and a half to eight million women. So we started just by looking at women over the age of 40, and we restricted it to those who, at least on paper, would be eligible for HRT.
So this excluded, um, women who had any contraindications, like history of breast cancer, ovarian cancer, stroke, um, coronary heart disease, deep vein thrombosis, a few other conditions. This was intentionally, like, a very conservative estimate of eligible women because we, we chose not to restrict the sample to those with a documented menopause or perimenopause ICD diagnosis code.
Um, those codes are notoriously underdocumented, so I think we would really be limiting ourselves there. Not to mention, there was a study that found that, you know, women with a menopause-related ICD code were more likely to report menopause treatment. So again, we don’t wanna bias our findings towards patients that are actively receiving HRT.
Um, we wanna show the good and the bad. And, you know, that’s sort of the nice thing about real-world data. They– It shows what actually happens at the point of care. So what did we find? The main takeaway is that HRT use among eligible women is increasing. Um, that’s good. In 2024, we saw that 11% of the women in our study had an HRT prescription.
So that’s, that’s more than double than, uh, what was reported in 2020 in that JAMA article that I mentioned That 11% was among women aged fifty and older. When we looked at women aged forty to forty-nine, the rate of HRT was about five percent in twenty twenty-four. And I should also note that the spike really started around twenty twenty-two.
That’s where we see sort of a notable upward trend. Um, our team is now finalizing the twenty twenty-five data, so we should have those numbers again, um, soon. We, we did not examine testosterone as part of this, even though we know it’s being used off-label for women. But for this analysis, we just stuck to the current FDA-approved options for women.
Now, I, I just mentioned that, you know, this analysis was limited to women without contraindications. We actually also did a sensitivity analysis where we placed no restrictions on these women, except being over the age of forty. Interestingly, the, the rates were pretty much the same among those with versus without contraindications.
Um, so that tells me that contraindications are not the primary driver of HRT underutilization. And so, you know, there may be women who are eligible but not receiving HRT, probably for different reasons. Um, and finally, one last thing to mention here is we looked at the distribution by age. Um, HRT use really peaked among women aged fifty-four to fifty-six.
Um, so the rate among them was actually seventeen percent versus eleven percent among kind of the overall cohort. So that peak aligns with the typical timing of menopause and kind of like what we think of, you know, the acute vasomotor symptom burden. However, we then see a sharp decline in older women.
So again, HRT seems to not– it’s not being driven by long-term maintenance, which is exactly what it was being used for prior to the WHI findings.
Marissa Plescia: Very interesting. And going off of that, you also conducted an analysis on physician notes about, um, HRT prescribing. What did you find here?
Janna Manjelievskaia: Yes. This was a really interesting component of the analysis.
Um, we took a sample of clinical notes, um, from women with HRT use in twenty twenty-four. We wanted to use the latest year available to us at the time. So again, this is a sample of women treated with HRT, and we’re looking at their physician notes from the point of care and trying to make sense of them.
So first, we looked at the notes around symptoms driving HRT initiation. Um, so why did these women start the medication in the first place? Um, vaginal dryness was the most commonly documented symptom. Um, it was followed by hot flashes, night sweats, and sleep disturbances. Um, other symptoms that were commonly mentioned were fatigue, joint pain, decreased libido, and urinary symptoms.
Um, that last one is important because we know that vaginal estrogen is extremely effective in preventing UTIs, which is one of the main causes of infections and hospitalizations in older adults. Now, earlier we talked about how HRT was widely used to prevent cardiovascular and other chronic diseases.
Our findings here when looking at the notes identified a gap in that. Um, a majority of clinician notes had zero mention of cardiovascular, uh, related benefits of HRT. There was no risk/benefit discussion as it relates to cardiovascular health. Um, outside of cardiovascular health, we looked, we looked at sort of the most common themes of just what was discussed between the provider and the patient, and the top theme was risk communication.
So to this day, you know, when providers are having conversations with their patients about HRT, they are leading those discussions with the risks associated with HRT. And what exactly is the risk that they are communicating? It’s breast cancer. So it’s, it’s really disheartening to see these data. You know, we are over two decades out from when the WHI was stopped early, um, you know, due to this alleged kind of risk of breast cancer.
Um, all of that has been disproven by modern science. We know the results were miscommunicated, and it’s, it’s amazing how much damage that has done. Um, I just wanna share a quick anecdote. When my colleague, um, Jordan Obercash and I, we, we presented some of these findings at the American College of Cardiology conference earlier this year.
And, you know, after our talk, um, we had multiple practicing cardiologists come up to us and say like, “This is exactly what we’re dealing with.” They, they’re telling us about, you know, patients in their practices who have been on HRT for decades. They’re not seeing breast cancer rates increase. They see women who are thriving.
They’re, um, not experiencing, you know, significant decline in age-related bone loss. And yet for years they’ve been told it’s too risky. So, you know, we can empower women all we want, but like I said earlier, um, the downstream effect of the WHI is there’s an entire generation of physicians that just does not know how to prescribe HRT.
Marissa Plescia: Yeah. Yeah. So well said there. Um, well, Jana, I just have one last question for you. What do you want healthcare stakeholders to take away from this report?
Janna Manjelievskaia: Hmm. Well, I think the takeaway is we have our work cut out for us. Um- Well, I, I would say, you know, this report gives us kind of a good overview of where things currently stand.
We’re able to take a large nationally representative sample of women, you know, from one of the largest ambulatory EHR databases in the US and examine these key trends. And we have to continue to build off this work. Um, it, it’s not gonna come as a surprise to anybody who reads the report that, you know, we have persistent gaps in diagnosis, in treatment, in aligning with evidence in women’s health.
Um, it’s also very clear across all life stages. So, you know, today we mainly discussed HRT ’cause it’s, you know, it’s a topic that’s gotten a lot of attention recently. But our report also highlights the fact that, you know, among adolescent girls, rates of mental health conditions, which were already not great pre-COVID, um, were amplified during that time and still haven’t returned to normal.
Um, in PCOS, which actually the name was officially changed yesterday to PMOS, um, polyendocrine metabolic ovarian syndrome, um, it’s supposed to sort of better reflect the actual nature of this condition. But in PMOS, we see delayed diagnosis, insufficient lab workups. They continue to be a huge issue. Um, and finally, you know, for the post-menopause crowd, we, like, we cannot continue to practice fear-based medicine.
Um, you know, so we need more data. We need those data quicker. And, you know, I, I’m just happy that our team got to contribute a really small piece to this massive puzzle.
Marissa Plescia: Yeah, absolutely. Well, Jana, this has been such an interesting conversation. Thank you so much for joining MedCity Fem Board. Really appreciate it.
Janna Manjelievskaia: Thanks so much for having me, Marissa. Yeah.
