“Perimenopause is the last black box in women's healthcare”
If science+medicine know nearly nothing about the human body during this stage, are the “experts” lying to us?
“How do we validate women’s experience without reinforcing a cultural script that says midlife automatically equals decline?” – Dr. Sarah McKay
Last fall, humor writer, Casey Rand, wrote a piece for McSweeney’s titled “Is it perimenopause or the fascist death knell of late stage capitalism?” perfectly capturing the perimenopause vibe of the moment — is this a perimenopause symptom or a psychosomatic response to an unjust world on fire? It’s hard to pick a favorite from her list, but here’s a good one: “Are my migraines hormonal, or am I thinking too hard about how Peter Thiel has more money than all nurses on Earth combined?”1
Super fun to hit a certain age and ride towards this hazy stage of body changes alongside daily snippet of news that seem hell bent on crushing any glimmer of hope for the future. Symptom or stress2? Chicken or egg? Eggless chicken? Both? Neither? All of the above?
Either way, the algorithms decided I’m ripe for targeting and up popped a promoted post for this steaming pile of crap – the Perimenopause Score (“with expert-backed insights!”) by Flo3:
Here is a company that launched in the pregnancy space squeezing its way into the menopause category with…. what the hell is this? A “Perimenopause Score” to show “impacts of symptoms”? That doesn’t even make biological sense. Symptoms are symptoms. They don’t impact things. They ARE the impact. Also, why would I find the “hidden impact” shocking? Are you going to tell me that the impact of hot flashes is that I might have sleep disturbances related to waking up in the middle of the night because I feel hot? SHOCKING!
I refuse to click and download the app to find out exactly what they are selling but, here’s my point — apparently, everyone wants in on this menopause gold rush.
Here is the part where I admit that I am conflicted.
While I do not think we need a company like Flo clamoring for a piece of the menopause pie with nonsensical clickbait (more on this below), part of me loves that there is a menopause gold rush. I keep thinking about a conversation I had in 2017, talking with a founder of a menopause company about all the ways she had to pretzel her pitch to emphasize the extent of the market opportunity. Less than ten years ago and she had to prove out the category because up until very very recently, innovation and entrepreneurship around menopause was a hard sell4.
Fast forward to today and we have beautiful celebrities making big pronouncements of “I will not stand for this taboo anymore!” alongside this Gen X meets Millennial perimenopause + menopause glow up, and it’s a hot topic. Great. Right?
Maybe.
Again, I’m conflicted.
On one hand, validation can have such a positive effect on how we perceive something as stressful – I feel this, this is what it is, this is what I can (or can’t) do about it. This is especially true when you have a medical professional validating how you feel and acknowledging your symptoms and concerns (vs dismissing them). For example, this conversation about pelvic health and symptom dismissal:
On the other hand, how close to the line are we getting between education+awareness and symptom searching in a way that negatively affects our response to the information shoved in our faces on a daily basis? The psychological can become the physical. The physical can become its own flavor of psychological stressor. There is a light side and a dark side to the mind-body-mind connection.
Brain fog is a perfect example of this. A real symptom that deserves acknowledgment. And a phantom symptom that we search for when seeking signs of perimenopause.
In this quick and clear IG reel, Dr. Sarah McKay, author of The Women’s Brain Book highlighted a 2021 longitudinal study that looked at cognitive issues across perimenopause. In the study, a majority of women did not experience any cognitive weakness (verbal learning and memory) and just as many women experienced weaknesses in those areas as the group that experienced strengths (25% for each group).
Building on these findings, Dr. McKay explained how our brains look to “match what it expects to experience or feel”, constantly scanning and making predictions in order to align with culturally perpetuated expectations:
“If you’ve been told brain fog is coming at 48, you’re probably going to start to notice every lost word or wobbly memory moment. That doesn’t mean it isn’t real, it just means that the story we are telling ourselves might shape the way we are experiencing it.
How do we validate women’s experience without reinforcing a cultural script that says midlife automatically equals decline?” – Dr. Sarah McKay.
Do we feel at ease having an excuse for the “wobbly memory moment”? Or is it making us worry about the inevitability of aging and everything that comes with it? Essentially – I’m in a body going through changes → here are the changes I might experience → that must be what this is… (even when it isn’t. ) Are we stressed by this? Or relieved?
The way our brain interprets stressors in our daily life relates to how we perceive control and predictability. Lack of control and unpredictability are fundamental elements that guide our brain in defining “stressor” vs “not stressor”. Perimenopause hits the stressor sweet spot in its unpredictability and lack of control. Plenty of body changes that we can’t control and can’t predict (and often don’t like because they are terribly inconvenient, exhausting, distracting, offputting, frustrating). Everyone’s experience is slightly different – e.g. I am dealing with acne and sleep disruption, a friend had frozen shoulder, another is having temperature issues, we all have different degrees of “moody”... and maybe some brain fog? But it helps to have a universal name for this thing that we can all gripe about together. How many group chats do you have that include the word “perimenopause”? I think I have five going right now.
Griping is helpful. Griping is validation. But griping is not solving.
But, even with that thought – what are we looking to solve for? Or what do we want to solve for? Expect to solve for? Is it relief from symptoms or fixing a problem? What are we told we can fix? Is “fixing” even a thing?
We do deserve solutions and relief and knowledge, but are we circling back up to look for problems? Are we feeling phantom symptoms because they popped up in an app served up by an IG marketing tool? Or are they real? Are we looking for problems to fix?
Questions aside, I do think the “fixing” is where I draw the line. When the education+awareness content focuses too much on the solution side, the “fixing” bit, without acknowledging that we don’t actually know all that much about the human body in perimenopause to “fix” any damn thing. For me, the line is unforgivably crossed when the “fix” is wrapped into educational content hiding a subtle menopause money grab5.
I worry that the menopause gold rush is muddying the water and hiding the real people, doctors, and companies that walk the right line of education and support6.
Rant (mostly) over.
If you’ve made it this far and are still curious about the true state of perimenopause research and healthcare, read on.
What do we actually know when research is undervalued, underfunded, and basic science is damn near IMPOSSIBLE
Women’s health is not well funded to begin with. Research on cycling female animals is historically lacking (and not getting any better):
At least with cycling animals and pregnancy/postpartum we have some animal models. Not with menopause. Certainly not with perimenopause. Very few species go through anything that resembles menopause so we do not have an animal model to run controlled laboratory studies (and I don’t think we’ll be studying whales as a model system anytime soon). Are there any other fields of medicine confined in this way? To understand the complexity of physiological connections, the interplay of hormones, the way environmental input affects biological output, researchers rely on model systems in a lab setting. We can take blood and tissue, dissect and examine, test and isolate. For obvious reasons, you cannot get to these levels of scientific discovery in humans.
What we do have for perimenopause is five longitudinal studies. FIVE. Most rely on annual check-ins with participants. Each are constrained in their own way7.
These studies are critical for the road ahead and I only highlight the constraints as a reminder, again, that we are decades, generations, away from understanding the human body during this phase of life. We should have an outcry about this. And we do to some degree, but it seems like there is far more skipping over this fact and jumping right to the outcry over symptom dismissal and medical gaslighting within the social media echo chamber of “we deserve answers NOW”.
I do support this outcry too. We absolutely do deserve answers now. But we need to hold the demands alongside the reality of the current state of science.
We’re far behind having the basic science for the answers and solutions8. But the social momentum has handed the microphone to those who skip the research gap outcry and, instead, fill in those gaps by reaching into the messy zone of extrapolation. This zone of extrapolation is a favorite play space of what I like to call “surface level experts” – anyone on the spectrum from the “person who read a thing and now knows a thing” (looking at you, wellness influencers who somehow manage to bend even real science into pseudoscience) but also includes those who hide behind extra initials (looking at you, MD / PhD / etc folks jumping into territory you never actually trained in or studied one bit9)
There is a wide spectrum from menopause grifter to surface-level-expert to actual expert. The lines between each can blur quite a bit. A tell tale sign of grift creep – do they admit the limitations of menopause research/knowledge (in a productive way) and are they trying to sell you something by speaking with definitive statements?
This came up in a recent conversation with Dr. Cynthia Stuenkel, a clinical professor at UCSD with over 80 publications on menopause including a paper titled “What is Menopause?” for the Menopause Society’s journal (she was a Founding Member and Past President of the North American Menopause Society):
“It's really important to know when to say ‘I don't know exactly.’ Even if you're an expert, there's stuff we don't know. [When I’m speaking, I’ll say] ‘anybody in the audience crack the code on this? Want to share with the group? Because I don't know the answer.’ Some people are not comfortable with that. The same people, I like the way you call it – the “surface level experts” – because they not only know everything, but they're ready to sell you something.” — Dr. Cynthia Stuenkel
Dr. Stuenkel has been in the menopause game long before it was cool. She opened the country’s first menopause program at UCSD in 1988 and the fact that she still asks “anybody crack the code on this?” says a lot about the state of the science here and how real experts could/should express humility.
“If it walks like a duck, and talks like a duck, it’s probably a duck”
I’m a hormone person. I wish we knew more about what hormones are actually doing during perimenopause. But we don’t. I’m coming to peace with that.
Most of what we know about the human body during perimenopause comes from the SWAN study, a longitudinal study that annually surveyed and sampled over 3000 women from 1996/1997 to 2022 (they started with an age range of 40-50). Hormones were annually sampled and with such a large sample size, that is generally sufficient to give a gist of average hormone changes across this transition period for the overall population (with some demographic breakout).
SWAN produced averages. Individual hormone levels are point samples. Even if you had LOTS of point samples from one individual, it still wouldn’t be a complete picture because we know so little about all the behind the scenes changes at a cellular or molecular level that would require sussing out with basic science research. All this to say, I think one of the biggest scams (and biggest red flags) is when a clinic offers hormone testing for perimenopause:
“The standard line is “don't measure hormones in women.” It is a moving target. We really try to go based on symptoms, age, walks like a duck, talks like a duck, it's probably a duck.
In a way, it doesn't matter what your hormone profile is if you're not symptomatic. I guess that's a bigger question: does your hormone profile matter? We've thought that through and, no, your symptoms matter.” — Dr. Cynthia Stuenkel
There is no (pharmaceutical) silver bullet
Treat the symptoms can come in the form of hormone therapy since hormone fluctuations and eventual drops are often the underlying factor (see below). But I worry that they might be offered as a bit of a short cut? I do love a good short cut and this is where we started for my sleep disruption issues when my doctor prescribed progesterone. But after taking it, we realized that progesterone was not exactly solving anything for me. Which means, I probably need to revisit other (more effective) tools.
But often the more effective tools require a bit of work (and privilege). And, really, most of the what we could be doing for our bodies and our brains during this stage might all come back to healthy aging and lifestyle:
“We have “treat the symptoms” and then we have – you're a middle aged person and there are things you can do to promote your heart health, your bone health, your mental health, your cognitive health, reduce cancer… They really all whittle down to lifestyle stuff. But no one wants to hear that.
I think it really is true that lifestyle is the silver bullet. But it’s hard. Some people don't have a safe place to exercise. Or they live in a food desert. All kinds of socio economic issues affect this.” — Dr. Cynthia Stuenkel
Also — turns out that addressing hormone loss is not the perfect solution for preventive care either:
“[Hormone therapy] never did turn out to be the preventive panacea that was hoped.
WHI was a randomized, placebo, controlled trial [looking at hormone therapy]. It was asking the question – if you take, “healthy” women who were ages 50 to 79 (at the start) and you give them hormone therapy, what happens? Will we reduce heart disease? That was the expectation. And then they looked at other outcomes like bone loss.
A lot of what's going on is aging. The fact that these estrogen studies just aren't quite turning things around shows that there is just no magic. The only group that we think makes sense for prevention are the women who have premature menopause because their body is being shortchanged.” — Dr. Cynthia Stuenkel
“It's such a messy time, physiologically, to define women.”
On that note, the one area that I have heard a certain menopause expert speak boldly about from a preventive care model has focused on the benefits of hormone therapy for cardiovascular health. Without even prompting a question, Dr. Stuenkel explained the issue this way:
“I think it makes sense to focus on cardiovascular health, but the data just isn't consistent. So within the medical field, people are doing this tug of war and it really confuses practitioners and women. I wish I could say ‘the experts agree’ and we could give a unifying story so you could think if I take it, it will reduce my risk of heart attack by 25%.’ You can’t say that now.
But the stuff keeps pouring out. We're getting this big flux of more observational studies with responses like: ‘wow, this is such an important report. I think we should act on this, and this should change practice.’ And I’m trying to remind everyone: ‘it's an observational study. It's subject to all the same biases. We had phenomenal observational studies 30 years ago. This is not a new concept.’
People are swayed by observational studies because the studies say what they want them to say. It really is tempting. But you have to stick with your hierarchy of evidence. It's such a messy time, physiologically, to define women. How would you say these are apples and apples when they're really probably all mixed up? You would need a huge number to really be able to look and separate – are they early? Are they mid? Are they late? Are they past?
Sadly, I don't know that we'll have trials with different kinds of estrogen. I don't know if we will have trials with perimenopausal women. We're under the spotlight, we need to know what to do, but even if the NIH wanted to launch research on perimenopause, they might not have money for that bucket anymore.” — Dr. Cynthia Stuenkel
Ah, women’s health research in 2025.
Treat the symptoms and embrace the placebo effect
I strongly believe in the physiological underpinnings of the placebo effect. I think it likely operates through the stress pathways by affecting our sense of control. A real physiological reason to explain how taking something with little to no effectiveness, seems to treat the thing that ails you. Just a theory, of course.
With perimenopause, we don’t have solid preventive care treatments but we do have treat the symptoms for relief… AND placebo effect.
“We do have things that we can do with hormone treatments. We have options. There is also the brand new sexy KNDy neuron-targeting Fesolinetant out there for hot flashes.
The other thing for people who are taking all this stuff and it's working is to consider how powerful the placebo effect is. For hot flashes, it is super powerful. Tell a patient, ‘take this, you'll feel better’ and they come back and go, ‘I do feel better.’ We see this in clinical trials, placebo could knock down hot flashes like 30% in some of these studies10. That’s huge. So you can give people all kinds of concoctions, and, I guess it’s our human nature that if they believe it's gonna work, it might work pretty well.” — Dr. Cynthia Stuenkel
Love a good placebo effect but what happens when a pharmaceutical (or supplement) has contraindications? Known or (worse) unknown.
“What else are we mucking with?”
We do not have basic science to effectively map the physiological changes of perimenopause. We don’t know how things connect in the body. We especially do not know how things connect in the brain.
Dr. Stuenkel brought up the issues with these gaps in the context of the new hot flash medication.
“I have a concern – because I’m a safety person – about what else we are mucking with when we start altering brain physiology for temperature control, reproduction, all kinds of stuff. I read some of the early papers about the effects of these things but I don't know if people are looking at these in the clinical trials. The FDA will say: show us that you reduce the number of hot flashes, show us you reduce severity, and show us you're not stimulating the lining of the uterus. The company that's going to market doesn't want to tease all [the other risks out]. They have to prove certain safety things, but they're not going to say, ‘oh, gosh, we didn't know we affected vasopressin.’ So then you see these [additional] risks in post-marketing. The package labeling will change.” — Dr. Cynthia Stuenkel
In addition, WHI — the longest running, longitudinal clinical study looking at hormone therapy — started with post-menopausal women at age 50. Only 30% of participants started under 60. There are no women younger than 50 in that study. I’m not going deep on this because there is no research to show if this is perfectly ok or less than ideal.
The biggest issue I see is that, as Dr. Stuenkel points out, we don’t know what we’re mucking with. We don’t know what mucks with what. And we certainly don’t know what happens when we start giving younger people hormone therapy because they feel like it is something they should get:
“My daughter is in her early 30s, and she said, ‘Mom, why haven't you told me what I should be doing for perimenopause?’ And I told her “I don't think you need to worry about perimenopause right now, you're like, 34 years old.” But when I told this story while giving a talk in Colorado, this young endocrinologist in the audience said, ‘Well, I'm so worried about this that any woman who comes in to see me, and who's 35 and older, I'm starting her on estrogen now.’
I just thought, ‘oh my gosh, this is kind of dangerous.’ I think we could see repercussions of these things depending how she gives it. We know there can be some other risks. It just blew me away.
I asked my colleagues, ‘Is this something new?’ Because I hadn’t heard about giving 35 year olds hormones, and yet, the more I talk and listen, the more I think it’s becoming more common. But it is totally unfounded!
I tell people that I think perimenopause is the last black box in women's healthcare. Other than the studies that looks longitudinally at what happens [e.g. SWAN study], we have almost no treatment data. And that's terrifying.” — Dr. Cynthia Stuenkel
Stop freaking us out, please and thank you.
All of this comes back around the primary issue at hand – education and awareness for validation and some semblance of control… NOT to make us feel like we need to buy your shit.
“The tail is wagging the dog. There's no way that science is going to catch up with the demand. Shame on people for making 30 year olds so paranoid. Perimenopause could be 20 years off. Go live a healthy life. Why make women so anxious that they're turning to these things out of fear or thinking someone must know the secret.” — Dr. Cynthia Stuenkel
It's great to normalize it, and it's great to not feel alone, and it's great to name it. It’s great to gripe. It's great to have the education and open conversation.
But let’s keep stay level headed here and not buy into the fear hype11
Last question (courtesy of Casey Rand):
“Am I irritable because my progesterone is low, or because social media has turned my prefrontal cortex into a 24-7 whack-a-mole game to sell me Norwegian wrinkle cream?”
Asking for a friend.
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I walk around saying this one a lot: “Are my breasts tender, or did I get punched in the tit by a Nazi?”
And there are plenty of stressors lining up at this time of life in addition to an unjust world on fire:
If you have read Amanda Hess’ excellent book Second Life, you’ll recognize this company.
Astounding when you consider how it affects over 50% of the population but then again, women’s health, in general, is still considered “niche” in some circles 🫤
The grifters in the cortisol space are numerous but the grifters in the peri/menopause space are exploding. The line between grift and good ‘ol fashioned capitalism is getting blurry (e.g. is everyone selling a proprietary supplement?)
There are plenty of folks striking a good perfect balance and not crossing this line. Out here in Substack land, personally, I prefer
writing at . I’m also keeping an eye out for a conversation that is recording with for . She had a great conversation about menopause and diet culture with recently.I know there is another very prolific and well known menopause expert on Substack now but I just can’t get over the way she will mention that “every woman deserves menopause care” while financially benefiting from menopause care only delivered to women who can hand over thousands of dollars out-of-pocket. Oh, and selling supplements. Very expensive supplements. With that said — can someone PLEASE explain the reimbursement structure for menopause care and if this out-of-pocket mishigas relates back to payer issues? Trying to find a good excuse for this behavior besides “capitalism”.
for example:
SWAN study — 3302 enrolled participants, 17 years, survey-based + annual physical and blood draw. Five racial/ethnic groups — 1,550 Caucasian, 935 African American, 286 Hispanic, 250 Chinese, and 281 Japanese.
Penn Ovarian Aging Study — 436 enrolled participants (67% retention), 18 years of approximately annual follow-up assessments for reproductive hormones for associations of hormone dynamics with physical and behavioral symptoms and genetic polymorphisms with trends in menopausal symptoms.
Menarche-to-PreMenopause (M-PreM) Study from the Australian Longitudinal Study on Women’s Health (ALSWH) — 1278 participants recruited bw 2019-2021, study ongoing.
Demanding individualized perimenopause care in 2025 is akin to a pre-antibiotic outcry for the right to survive an infection. We know VERY LITTLE.
We're all inclined to overextend and overstep expertise. I know that I do this too. And, to some degree, going beyond expertise is an important part of extending the conversations. BUT there is a fine line in how people present as THE expert on a thing without highlighting actual experts or, worse, outright dismissing them.
(and if someone says any form of “estrogen receptors are everywhere, therefore, loss of estrogen affects everything!” one more time, I might seriously lose my shit)
This is also really interesting in the context of the brain fog study. The women who showed signs of cognitive/memory issues were also the ones experiencing hot flashes and sleep disruption. Is brain fog just related to crappy sleep?!
And, please, for the love of all things holy, do NOT get a pellet inserted.
Just wanted to say I really appreciate and enjoy your writing Molly, and your commitment to honesty and science. Keep going!
Have you read the Hormone Repair Manual by DR Lara Briden, ND? She draws on work done by Dr Jerrilynn Prior at the University of British Columbia. She has many publications and established CeMCOR -the Center for Menstruation and Ovulation Research. They have a different perspective on the perimenopause. They see the menopausal transition as natural and not a deficiency state. They stress the importance of ovulation for the production of one’s own progesterone and recommend progesterone therapy (among others) to ease the symptoms of perimenopause. And, neither Dr Briden or Dr Prior sell anything other than books!