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Welcome to The Modern Midlife Collective—where midlife isn’t a crisis, it’s a rebirth. Hosted by Dr. Ade Akindipe, DNP, and Dr. Jillian Woodruff, MD, this is the podcast for women ready to unapologetically own their power, thrive through the ups and downs of hormones, weight, and self-care, and show the world that thriving at 40 and beyond isn’t just possible—it’s your birthright.
Biweekly, we bring you science-backed insights on hormones, menopause, longevity, and sexual health—real tools to empower women in midlife and beyond. With a fearless blend of functional medicine, real-life wisdom, and no-nonsense empowerment, we’re here to challenge the norms, break through the barriers, and help you step into a life of vitality, confidence, and unstoppable strength.
Ready to rise? Let’s do this.
speaker-1 (00:00)
Okay, so back in episode 20, we told you about the estrogen lie, the FDA quietly walking back twenty years of black box warnings on hormone therapy products. That episode hit a nerve. But here's the thing about correcting one kind of misinformation.
speaker-0 (00:16)
And yes, sometimes you swing straight into a different kind of misinformation.
speaker-1 (00:20)
Exactly. So today, this is a quick one. We're doing an update. Not hormones are scary, not hormones are magic, but we're gonna walk through what's actually in the research, new research that's come out this month, what it does and doesn't show, and where the current hype train has gotten ahead of the data.
speaker-0 (00:38)
All right, let's go for it.
speaker-1 (01:36)
Fast recap for anyone new. In 2002, the Women's Health Initiative, a huge randomized trial.
speaker-1 (01:43)
Was stopped early because the hormone group had more breast cancer, strokes, blood clots. and the information that this was happening with people who took hormones was what hit every front page in the country. Hormone therapy prescriptions collapsed almost immediately and stayed low for like two decades.
speaker-0 (02:03)
Yeah, and that was based on that fear was based on real data. So we're not here to say that the WHI or the the Women's Health Initiative was fake news. It certainly wasn't. It was definitely real. It was a randomized control trial. So the problem is the problem there was how that data got translated and sent broadly to all women.
speaker-1 (02:25)
Yes, so let's do the thing we always do, relative risk versus absolute risk. When you hear hormone therapy increases breast cancer risk by so much percent, that's a relative risk. It sounds huge. What actually happened in the WHI's estrogen plus progesteron arm was about eight additional breast cancer cases per 10,000 women per year compared to placebo. Eight additional breast cancer cases.
speaker-1 (02:53)
per 10,000 women per year. So very different than the percentage that hit the headlines. For heart disease, there were about seven additional cases per 10,000 women years. For stroke, about eight more cases per 10,000 women years. So those are real. They're not nothing, but they are absolute numbers you can actually picture. Not a scary percentage floating in in space there.
speaker-1 (03:20)
And here's the part that almost never makes it into the popular retelling that was told at that time. The WHI also had an estrogen-alone arm. These people only took estrogen. They'd had a hysterectomy, so they weren't taking progestin to protect their uterus that they didn't have. That group did not show more breast cancer cases. It actually showed fewer cases, about eight fewer cases per 10,000 women over six years. Worth being precise on those statistics there.
speaker-1 (03:50)
And that reduction didn't reach statistical significance, which is how we say if a result is left to chance or not. It didn't reach it immediately during the active trial itself, but it did reach significance in the longer term follow-up, alongside a reduction in breast cancer mortality. Very important information to know.
speaker-0 (04:09)
Yeah, and that's the great thing about, you know, research, right? It's great that they could walk back, go to that data and actually look at it and extrapolate how that looks now, right? So it's great that we can say estrogen alone, lower breast cancer risk, estrogen plus that specific synthetic progestin higher. So that's a completely different story than hormones cause cancer. Everybody get off their hormones now.
speaker-0 (04:35)
And you know that unfortunately that's what's been happening over the last, you know, before after that study and was released and you know all the results came back. but here we are today and that there's one more variable that got lost in that too when WHI researchers went back and split the results by age at starting therapy. Women in their 50s who took estrogen alone actually had lower heart disease risk and lower.
speaker-0 (05:02)
mortality. And I've been actually fairly excited about that since I saw that. Women in their seventies starting more than a decade after menopause had higher heart disease risk. So same drug, opposite direction, depending entirely on when you start. So timing really matters. That's what researchers are now calling the timing hypothesis.
speaker-1 (05:21)
Right. And that matters because the average WHI participant was about sixty-three years old. And two-thirds of them were over sixty at enrollment, most more than ten years past menopause. And so that's not the typical patient asking about hormones for hot flashes at forty-eight, at fifty-two, at fifty-five years old.
speaker-0 (05:43)
So true, so true. Yeah. So fast forward November tenth, twenty twenty five, you know, the HHS, the Health Human Service and the FDA held a press conference and announced, and I remember this very clearly, they're removing the black box warning from hormone therapy labeling. And so that's the news we covered back in episode twenty.
speaker-1 (06:05)
Yeah, to be precise about what changed, the warnings being removed cover cardiovascular disease, breast cancer, and what was labeled probable dementia. However, it should be said that there is a real and well-established risk of uterine pathology if estrogen is given without something to protect the uterine lining. And we usually use some sort of progesterone when we're giving estrogen.
speaker-0 (06:28)
Exactly. And the FDA's reasoning was that the original warning language came out of the 2002 WHI data we just talked about in a population that skewed a decade or more older than typical patients on one specific oral formulation. And that two decades of follow-up and reanalysis plus a July 2025 FDA expert panel.
speaker-0 (06:52)
and a public comment period supporting updated the so that's what supported the label to reflect that age stratified, time dependent reality instead of that blanket statement for all women. It was the women that started later in life that probably were postmenopausal and maybe even had those risk factors already or who they who those were affected.
speaker-1 (07:14)
Yeah. They also approved a generic version of Primarin, the first one in like thirty years, and a second non hormonal option to treat menopause symptoms such as hot flashes. So that's pretty exciting.
speaker-0 (07:29)
Yes, absolutely. And we want to flag something here too, in the spirit of not sc you know, no scare tacting and also not cheerleading either, right? This was a regulatory and communications decision as much as a new discovery. The data didn't change overnight, right? In November 2025. What changed was how regulators weighed this 20-year-old evidence against newer, larger, you know, analysis. So
speaker-0 (07:55)
The good news is that evidence-based decisions in our view, but it's a policy shift building on existing research. So there's still a lot of transitioning happening. You may not necessarily get, you know, it it takes it takes a while for things to translate into practice. So you might see some things kind of taking some time. Maybe you might have some providers still kind of not wanting to prescribe it yet. But this is just telling you that the research is changing and you have more options. So
speaker-1 (08:22)
Yeah, well this that's a good bridge into why we're doing today's episode because the reaction to that polish policy shift has predictably overcorrected in the other direction. So, you know, let's talk formulation because this is the piece that gets flattened every time this topic goes viral. What did WHI actually test? They tested oral conjugated equine estrogen. So the brand name of that is permarin.
speaker-1 (08:48)
And it's derived from the urine of a pregnant horse. And so it not only has the estradiol that we, you know, have in our bodies, but it has some various other estrogen types that the human body does not have. And for the combined arm, they use that primerin plus oral madroxy progesterone acetate, which is a type of progesterone. The brand name for this would be Provera.
speaker-1 (09:13)
And so together, when they put those together, they call that primpro. And so both are synthetic derived and both taken as a pill orally.
speaker-0 (09:23)
Yeah, and so what do we typically reach for now in 2026? And for most patients it's the patch, the the transdermal estrodiol, a patch or a gel which is considered bioidentical, meaning it's molecularly identical to what your body normally produces. And it skips over that liver metabolism, what we call the liver's first pass, which is why of you know it carries a lower clotting risk.
speaker-0 (09:50)
than the oral estrogen. And on the progesterone side, oral micronized progesterone, the brand name you'll commonly see in the pharmacy is prometrium, which is also bioidentical and rather than the synthetic progestins that was used in that study, the WHI study.
speaker-1 (10:07)
You know, yes, not to get too much into it, but that's so interesting because the synthetic micro micro madroxy progesterone acetate is not interchangeable with micronis progesterone, our bioidentical progesterone type, right? The madroxy progesterone acetate has it's it's highly potent and it has an affinity for non-progesterone receptors as well.
speaker-1 (10:33)
So it does even more than what it's intended to do. It binds to glucocorticoid receptors and androgen receptors as well. And it has effects on your blood vessels, on your nervous system, on breast tissue that mycronized progesterone doesn't have. And like to put it in perspective, when you're giving the dose needed to protect your uterine lining.
speaker-1 (11:00)
Madroxy progesterone acetate, that dose is like 2.5 milligrams per day. Whereas to get the protection using micronized progesterone, you need like 100 to 200 milligrams per day. So the potency is different. What they attach to is different. Our bioidentical progesterone also attaches to those GABA receptors in our brain, leading to relaxation, which is identical to what our endogenous, the progesterone we make.
speaker-1 (11:27)
you know, attaches to.
speaker-0 (11:28)
Absolutely. Lock and key. I always think I always think of a lock and key when it comes to these things. So when someone says hormone therapy causes strokes and blood clots, look at the WHI. The honest answer is that specific oral synthetic combination in that age group did increase blood clots those risks altogether. It's not automatically true of a transdermal patch, with micronized progesterone in a fifty-two year old, you know.
speaker-0 (11:53)
Who just had her last period three years ago? So different drug, different route, and a completely different population.
speaker-1 (11:59)
Right. So we have to be careful not to overcorrect into bioidentical is just automatically safer. No. The strongest evidence we have specifically testing transdermal estradiol plus micronized progesterone in a randomized trial is the KEEPS trial, the Kronos early estrogen prevention study. That was a randomized placebo-controlled trial. women were within three years of menopause with no existing heart disease.
speaker-0 (12:26)
Yeah, that trial really found some, you know, real symptom relief and preserved bone density with both an oral estrogen arm and transdermal estrogial arm, each paired with micronized progesterone. So both of them had, you know, that endometrial progester protection with micronized progesterone. It did not find a benefit on a marker of early atherosclerosis or plaque in the walls of your arteries called
speaker-0 (12:53)
carotid intima media thickness and the oral and transdermal arms actually differ a bit from each other on mood and cognition measures too.
speaker-1 (13:03)
Yeah, so what you take and how you take it matters. Mm-hmm.
speaker-0 (13:05)
It definitely does.
speaker-1 (13:07)
There's another observational study from a French cohort called the E3N, and it suggests estrogen paired with micronized progesterone may carry a more favorable breast cancer risk profile over time than estrogen paired with older synthetic progestin. So we do want to flag that to cohort data, not a randomized trial. So it can show an association exists but can't be used to
speaker-1 (13:32)
Prove that the progesterone choice is what's causing the difference.
speaker-0 (13:36)
That's a good point. Okay, so here's where we get to why we're recording this episode right now. Since that FDA announcement, hormone therapy has had a real moment on social media, right? You'll see it everywhere. NPR ran a piece on August seventh basically asking, is this being sold as a cure all?
speaker-1 (13:57)
And the honest answer is in a lot of corners of the internet, yes, we're seeing claims that hormone therapy fights wrinkles. I think we did talk a little about that. We did. that it melts away the weight, that it cures your your brain fog, that it grows your hair back, prevents heart attacks outright. It's really just a longevity drug. So Stat News ran a piece back in January calling this the third time.
speaker-1 (14:22)
In about ninety years, that hormone therapy has gone through this exact like hype cycle. And they even flagged the language from the FDA, like an FDA official said something about hormone therapy saving their marriage and rescuing women from depression. So some of these are just really blanket overstatements and oversteps.
speaker-0 (14:41)
We're not gonna pretend that's responsible messaging, right? Even coming from an official source, hormone therapy is a well-studied treatment for specific things. and there very well could be a lot of the benefits. I mean, these are like subsequent things that are happening, like maybe women are improving their sexual health. So now they're having better relationships, maybe their mood is more stable. So there's a lot of significant benefits.
speaker-0 (15:05)
But of course there still needs to be that risk stratification, talking to your provider and making sure this is right for you. So it's not a blanket statement that hormones cure all is what we're trying to say.
speaker-1 (15:14)
Yes. Okay, so what's actually well supported, we of course have strong evidence, hot flashes, night sweats, which affect up to 80% of women in the menopause transition. vaginal dryness and irritation, bone loss prevention. Those are like three pillars with the best data behind them that are benefiting from hormones.
speaker-0 (15:33)
Yeah, not currently supported by strong evidence, meaning major medical organizations don't recommend hormone therapy for this specifically, using it purely for longevity or heart disease as a primary prevention goal, for skin appearance or just general just preventing chronic conditions. That doesn't mean none of these things are affected positive, aren't affected positively by hormones.
speaker-0 (15:57)
It just means we don't have trial evidence solid enough to prescribe it for those reasons alone. You know, we always go with the evidence. We don't just make these big claims. Just like the WHI, right? You don't wanna just do a blanket thing and say, Okay, this is what we're gonna do for everything. It just doesn't work that way.
speaker-1 (16:12)
Exactly. I mean that's a that's a great point. And the stat piece makes a fair point we want to own as well here today. A lot of the original enthusiasm for hormones back in the 90s came from observational studies where women who took hormones also happened to have fewer heart attacks. That's kind of what led to that study. But those women were also, on average, wealthier, more likely to exercise, less likely to smoke. So that's
speaker-1 (16:39)
Confounding. That's a confounding piece. So it's not causation. And it's a big part of why the WHI, an actual randomized trial with such an important with such an important like gut check, really.
speaker-0 (16:50)
Hmm. So where we land, the FTA's label change was a reasonable, evidence based correction. We're so grateful for that. Yes. Fountain of youth marketing that followed, not necessarily. but both things are true at the same time and you can hold both.
speaker-1 (17:06)
Yes, I think, you know, we obviously are pro hormone. We absolutely are. Absolutely. but we're also pro evidence-based medicine as well. And really pro women making the decision that's right for their bodies. So I don't want you to be led like this is the fountain of youth. Are there some benefits? Yes. Is this something that we should recommend for everyone to do? No. It's it's understanding what risks are to you.
speaker-1 (17:34)
And what benefits may be specifically to you. Personalized medicine, that's what we're always talking about.
speaker-0 (17:39)
Right?
speaker-1 (17:40)
So the last piece, and this is a big one, this month, a team of Stanford researchers published a study in the Journal of Neurology with three separate parts looking at hormone therapy and Alzheimer's risk. The first part looked at autopsied brains, about 2,900 women across two different databases.
speaker-1 (17:58)
Roughly 260 of them had used estrogen-only hormone therapy in their past, and found they found significantly less of the plaque and tangled buildup that's associated with Alzheimer's disease in those autopsied brains. That's a 35% lower likelihood of Alzheimer's. And that one reached statistical significance. So there was there was some causation there.
speaker-1 (18:24)
The study's other two parts, actual dementia diagnoses over time, and looking at their blood and spinal fluid biomarkers for Alzheimer's, both pointed in the same direction, including a roughly 40% lower odds of a dementia diagnosis, diagnosis in those people who were on estrogen, estrogen-only hormone therapy.
speaker-0 (18:44)
Hmm. A few things to slow down on here. First, this is an observational study, not a randomized trial, right? so in every part of it. So these are women whose records, brains or blood and spinal fluid were studied after the fact, not assigned to a hormone therapy or placebo by researchers, right? The aut the autopsy data in particular came from women whose brains were donated after death.
speaker-0 (19:09)
and researchers looked back at whether they'd used hormone therapy or not. researchers did adjust for age, you know, what their genetic Alzheimer's risk was, their race, education, and blood pressure history, which is really a good that's a really good practice. But an adjustment isn't a guarantee against every possible co founder. So women who chose to take estrogen therapy and stayed on it for years may differ from women who didn't in ways that are hard to find.
speaker-0 (19:37)
fully capture. So sometimes cause that's sometimes called a healthy user effect. So healthy user effect.
speaker-1 (19:43)
Yes. The researchers themselves were really careful to say it shows an association in their words doesn't cause or address causality, given that re retrospective design of the study. So yeah.
speaker-0 (19:55)
Yeah, right. And this is important for anyone listening who's on combined therapy, not estrogen alone. This study specifically tested estrogen only therapy. It did not draw a conclusion about estrogen plus progestine therapy in either direction because too few of women studied had used the combined regimen to analyze. that is not the same as the study find finding no benefit for combined therapy. So it it's
speaker-0 (20:22)
an absence of data, it's it's that doesn't mean that there's a negative result. We just don't have enough data for that. So if anyone's telling you the new Stanford study proves combined hormone therapy doesn't protect the brain, that's not what happened. The study simply didn't ask that question with the estrogen only sample it analyzed.
speaker-1 (20:41)
Yeah, and there's older data pointing a different direction for combined therapy, but we need to be precise about which combined therapy. And we talked about this earlier. So in 2003, the WHI memory study was an ancillary randomized trial to the original WHI, and it found a hazard ratio of about 2.05 for probable dementia in the combined arm. Roughly double the risk versus placebo. So
speaker-1 (21:08)
Relative risk. Again, relative risk, right? so and this was found in women who started their hormones, the combined hormones later in life. But the actual product tested was one specific drug, the oral conjugated equine estrogen, so primerin, with madroxy progesterone, acetate. That's that synthetic potent progesterone we talked about. So the same Primpro combination from the original WHI. That's not the micronized bioidentical progesterone most of us use today.
speaker-0 (21:34)
That's right.
speaker-1 (21:34)
Right.
speaker-1 (21:35)
And the biological reason people think that distinction of progesterone type matters is, you know, what we talked about earlier, but also that madroxy progesterone acetate kind of blunts some of estrogen's protective effects on the brain. things like how it supports growth factors and helps clear that amyloid product protein from the brain. And so that comes from lab and and animal data, not a human trial.
speaker-1 (22:01)
proving it. So it's a plausible mechanism of why the madroxy progesterone acetate may have caused or may have led to the higher risk in the combined patients, or why micronized progesterone may not have those same risks, but it's it's not a settled explanation.
speaker-0 (22:18)
So does that mean micronized progesterone is off the hook? Well, that's genuinely unresolved. On the randomized side, specifically for micronized progesterone, you know, it keeps again the same trial from earlier, right? It's it's cognitive arm that keeps cog put recently menopausal women on either oral estrogen or transdermal estradiol, but both paired with cyclic micronized progesterone.
speaker-0 (22:46)
against a placebo and they tracked their congri their cognition, you know, their brain health for four years. And the result was neutral. There was no cognitive benefits, no cognitive harm in either home hormone arm. the important caveat on that too is, you know, in fairness, four years is, you know, r you know, relatively a short time. It measured cognitive brain function performance in women in their forties and fifties.
speaker-0 (23:11)
not a dementia diagnosis decades decades later, which is what the WHIMS and those cohort studies actually tracked. So that study tells us micronized progesterone didn't hurt short-term cognition. It can tell us about the long-term dementia signal because that specific trial hasn't been run.
speaker-1 (23:31)
Yeah, so our honest bottom line on this piece, the clearest best documented dementia harm signals traced to one specific combination, oral estrogen, conjugated equine estrogen, plus madroxy progesterone acetate in women who started later in life. So more than 10 years past menopause. Whether the micronized progesterone most of us prescribe now carries that same risk is an open question. It's not resolved.
speaker-1 (23:58)
And so anyone who tells you bioidentical progesterone is proven safer for the brain is just overselling the data. But so is anyone who tells you that every progesterone carries the same risk, because we know that's not true either.
speaker-0 (24:12)
That's right. The honest summary for the whole segment, promising on estrogen alone, worth watching. Absolutely not settled on combined therapy of any kind, and not yet a reason to start or continue hormone therapy specifically to protect your brain.
speaker-1 (24:25)
Right, not starting specifically to protect your brain. Yeah. I hope that's clear. So if you're listening and trying to figure out what to actually do with all of this, here's where the two of us land. In our view, hormone therapy, and of course, you know, correct me if I'm misspeaking for you, okay? But in our view, you know, hormone therapy remains a genuinely good option for a lot of women.
speaker-1 (24:48)
They're navigating the menopause transition. And we're talking about ha those who have the classic symptoms of hot flashes or night sweats or vaginal dryness or even bone density loss. So needing bone protection. But also for those with the ripple effects from those symptoms that those symptoms kind of drag along with them. So they the broken sleeve, the daytime brain fog, the painful sex, the low libido.
speaker-1 (25:13)
mood swings, the whole constellation of things that can quietly erode your quality of life. Those are real. They are also treatable. And for many women, especially those who start within about 10 years of their last period, our honest read of the evidence is that the benefits in those situations for many people outweigh the risk.
speaker-0 (25:33)
Absolutely. And we want to be careful with the word benefits, right? Because that's the part the internet keeps inflating. You know, when we say the benefits outweigh the risk, we mean for treating the symptoms that are actually in front of you right now. Like Dr. Jill just mentioned, that's where the strong evidence lives, you know, the hot flashes, the night sweats, vaginal dryness, bone protection. What we're not saying and what the data does not support is starting hormones as a longevity drug.
speaker-0 (26:01)
Or to prevent heart disease. And this is the fresh one from today's episode. To protect your brain from Alzheimer's, you know. That's estrogen only that estrogen only signal is genuinely interesting. But it's an association in observational data. It does not translate into a prescription for brain protection. Not yet. Anyways, we hope maybe in the future.
speaker-0 (26:25)
Treat the symptoms, not the headline. So that's the important thing we want you to understand.
speaker-1 (26:28)
Well said. And the second thing we tell you formulation matters and it's worth being an informed consumer about this. Ask your provider exactly what you're being prescribed. Is the estrogen oral? Is it transdermal? Is it injection? Is it a pellet? Because the non-oral root genuinely carries a lower or maybe even negligible clotting risk. And is the progesterone a bioidentical or synthetic progestin? Those are not interchangeable when it comes to the risk profile.
speaker-1 (26:57)
for for many things, not just Alzheimer's, but for many other risks that they find in hormone therapy. so the formulation matters. Know what you're being prescribed and how you're being prescribed it. So that's our update. That's our update. we'll be tracking that one as more data comes out, especially anything about the combined therapy, and we'll bring that to you.
speaker-1 (27:19)
I think that's all we have. But before we go, if this quick update was useful, hit follow or subscribe wherever you're listening to this podcast so you don't miss the next one.
speaker-0 (27:29)
Absolutely. And if you've got 60 seconds, 30 seconds even, leave us a rating and a review. This allows other women like you to sh to just get some information, this update. It generally helps midlife women find this show.
speaker-1 (27:42)
Yes, if you have a question for us about your own hormone therapy or something you want us to cover here, then email us at connect at modern midlife collective.com. And for links to everything we've mentioned today, see our show notes or head to www.modernmidlife collective.com.
speaker-0 (28:01)
Thank you so much for listening.
speaker-1 (28:02)
We'll see you next time. Goodbye.