Ep 88 Endometriosis: Menstrual Backwash

get past it was a little bit of ibuprofen. I was also raised very religious, and I'm still quite religious, and unfortunately, some American puriody culture crept into my upbringing, and so I didn't spend a lot of time thinking about, for lack of a better word, my reproductive parts.

it wasn't a very big deal. It was just something that was in my head and I was able to move past it. In our first year of marriage, I got pregnant unexpectedly and had no problems with the pregnancy except that it was I was very nauseous through the entire thing. I was in a lot of pain, and then when I had to have cervical checks, I was in tremendous amount of pain. Again, I told them that I thought this was due to growing up with a certain amount of purity culture and that it was psychological,

and nobody questioned it. So after I had my daughter, eventually my period returned and I started having worse and worse cramps. But everybody tells you that after you have a baby, your periods get worse. That's just what people tell you, and so once again I chose to disassociate from it and ignore it. Some of the painful sex symptoms subsided, others remained. Mostly I was just proceeding with

business as usual. Last year, I started having cramps so bad that I would have bladder spasms, which means that I would literally be my pants with no control. It only happened a few times, thank goodness, but I also ended up starting to have to lie down when I had my cramps, and I was surprised that it wasn't great, but I could generally manage it with like three to four ibuprofen and heat pack. But by the fall, things had escalated and the ibuprofen wasn't cutting it, and the

heat pack wasn't cutting it, but the killer was. When I noticed that there was blood in my stool, I didn't really want to do anything about it, but by January, my sister told me that I had to do something about it, so I went into urgent care. They took some samples and told me that I needed a colonoscopy and that I should not have any ibuprofen until after

I had the colonoscopy. Then on my thirty fifth birthday, I spent the entire day in agony and the worst pain I've ever had because I was experiencing my cramps without any sort of pain blocker. I went in for a colonoscopy at the beginning of March, and I didn't expect them to find much of anything, because again I didn't really believe that I had any problems, and I thought to myself, the only problem that I could really have is cancer, because cancer runs rampant in my family.

convinced I was going to die. I also delivered the news to my family and told basically everyone I know, because I decided that if I did indeed have cancer. I wanted everybody to start praying as quickly as possible, and I maintained that it worked, because a week later, the same doctor called me back and told me that the cell simples, to his great shock, had come back not as cancer but as endometrisis. I literally fell to.

mostly it was horrible endometriosis. So she showed me the images that they had taken of my body in the MRI and everything, and you could see that there was something growing out of my left ovary into my colon, and we knew that it was probably in other places. But there is no way to confirm endometriosis except by surgery, so they could not confirm, and they thought there was

a possibility that there was still cancer. So the other thing that the guynok told me was that she thought I was going to have to have a complete hysterectomy and eupherectomy. I had been trying for a second child at this point for almost a year and this was devastating. But because there was a chance of cancer, I was like, just take it all.

the surgeon was able to do it. There is still an insignificant amount of endometriosis on my right ovary, It's less than one centimeter, but they were able to remove fourteen point five centimeters of.

had no idea that I was in pain. The emotionally challenging part of this, aside from thinking that I was going to die of cancer for a fairly significant amount of time, was that there's almost no chance of me ever having another biological child, and so I've had to give up on that particular dream because the hope was just too much. But we got a puppy, and so that's my replacement baby. I have also learned to be a lot kinder to myself and to trust my body more.

I accept now that I am living with a chronic illness. I try to take naps a lot, I try to listen to what feels good and what feels bad. But when I stopped to really think about it, the thing that really makes me angry is that I had no

idea I had endometriosis before any of this started. It is absurd that no one thought of endometriosis, that I was never presented with any education about endometriosis, that no one in my friend's circle ever talked about endometriosis, even though I found out more and more people have it, and I just feel like I know so little. In a post I wrote on Reddit, i wrote, I've been a feminist for my entire life without understanding that I've

been trapped in a patriarchal pain and trap. So thank you for listening to my story.

With that, Aaron, should we just get into the endometrium of this episode?

uterus or has endometriosis. Number two. It ignores the fact that endometriosis, pain, and endometriosis itself can persist or even sometimes arise after menopause aka after quote child bearing. Number three. It also ignores the fact that cases of endometriosis, though very rare, have occurred in people assigned male at birth, which means that a uterus isn't necessarily a prerequisite for

the disease. And finally, and I think most importantly, I don't know they're all important, but by designing this disease to this particular group, quote, women of child bearing age and Aaron, I know you're going to talk a lot more about this.

personal favorite organ, the uterus. That's my favorite one. Do you have a favorite organ?

how you can think of them. That surround these glandular cells and this endometrium, This inner lining of the uterus is constantly in flux. This lining is what responds to and changes with the influence of cyclic variation in our hormone levels, most specifically estrogen and progesterone. This is the menstrual cycle that we went over in our birth control episode,

which was now a couple of years ago. To recap it, under the influence of an increase in estrogen, oocytes in the ovaries begin to mature, and the uterus lining the endometrium proliferates. It grows in number, these stromo cells and these glandular cells, and this is known as the follicular phase or the proliferative phase, where this lining is growing and the endometril lining is becoming thicker in preparation for

the potential implantation of a blastocyst. Then that peak of estrogen prompts a surge of another hormone that causes the

release of an egg aka ovulation. And then as that surge of estrogen declines, progesterone, another hormone, begins to increase and the uterus the endometrium enters what's known as the secretary phase, where these glands thicken and the arteries within their widen and proliferate in number, and the endometrium undergoes this process further preparing it for receiving a blasticist and then without anything that implants, fourteen days go by and

progesterone levels sharply decline, and this withdrawal leads to the separation of all these cells from their basal layer and they slough off, aka menstruation. All of that endometrial tissue then exits through the cervix, which is the opening of the uterus through the vagina, and that is menstruation, right, yep, right, okay.

So if that all is the menstrual cycle, and that's what's happening inside of a uterus during that menstrual cycle, then what is endometriosis If it's the finding of these same type of cells that are found inside of a uterus, these endometrial, glandular and stromal cells, but now they are

implanted in tissue outside of the uterus. So instead of being inside the lining of this muscular organ, it's outside on the wall of the organ, or on the wall of your belly, which is called the peritoneum, the inside wall of your abdomen. It could even be on your bladder or in your Philippian tubes, or on your ovary, or on your rectum. It could be anywhere literally in your body. So then the question is how does this become a disease or a problem, Like, why is it

a problem to have this tissue outside of the uterus. Well, this tissue is still active. It's hormonally sensitive endometrial cells that are undergoing the same proliferative and secretary and then degeneration that happens within the uterus and would end in mensies leaving the body through the vagina, but it's happening in an abnormal location and therefore leading to not only abnormal responses in our body and massive amounts of inflammation, but it's also then not able to leave the body,

so this inflammation still contained within the body. That leads to tissue damage, which can then lead to scarring and fibrosis, which leads to the symptoms of endometriosis, which are chiefly pain, which doesn't begin to describe adequately like the true symptoms, and also infertility or difficulty conceiving or sustaining a pregnancy. So that was a lot, like all in a very short amount of time. And that's all we know about endometris'. Is just kidding, We know like a tiny bit more

than that. Yeah, So that explanation left a lot of open ended questions, and I think the first one that I would like to be able to answer is how how does this endometrial tissue end up in a place where endometrium shouldn't be tissue types in our body, like

different cell types are actually pretty tightly regulated. So like, the tissue that makes up our lining of our abdomen is different than the tissue that makes up the lining of your uterus, which is different than the tissue that makes up your heart or your blood vessels, et cetera.

which is the effect? Right right, But yes, that can be part of the problem because our body does recognize when a tissue is not in the right place a lot of times. But again, this doesn't happen very often to have a tissue type in a location in the body where it doesn't belong, because in general, as we develop from a single cell all the way into our multicellular human cells, our cells undergo this process of differentiation into all of our specific tissue types in a very

characteristic pattern during the process of embryogenesis and development. So all of our cells have very explicit sets of instructions that they follow and explicit influences that they're under in order to develop into these different tissue types in certain areas and not in others, which is why we don't see heart tissue in our bones or brain tissue in our guts for the most part. So why on earth do we sometimes get endometrial tissue outside of the inside

of the uterus? And the short answer is, we don't know, we don't know, we do not know. Let me go through the quote prevailing theories and then maybe erin you and I can have some opinions. So the kind of what's obnoxiously still called the prevailing theory on how this happens, on how endometral glands end up implanting and then replicating and proliferating outside our uterus is something called retrograde menstruation or what do you call it erin.

So during menstruation, all of the endometril lining and tissue comes out through the cervix, which is the base of the uterus and also the top of the vaginal canal that is the normal flow of menstrual products. But the top of the uterus, those Filippian tubes are open at the ends. So in fact, there is in many people who menstright menstrual product aka endometrial tissue that goes backwards and it goes out through those Filippian tubes and enters

our peritoneal cavity. That's it backwash, backwash, And it was thought that this certainly must be the way that endometriosis happens. These endometrial tissues are entering our peritoneal cavity. Boom, there you go.

But as it turns out, this is very common and happens in at least, if not more than about forty percent of people with the uterus who men straight pretty much every time they menstraight to varying degrees. So it doesn't explain why some people then go on to develop endometriosis and others don't. It also doesn't explain how endometriosis can happen in people without a uterus to begin with,

which again is incredibly rare but has happened. And it doesn't explain how endometrio cells can end up outside of the abdominal cavity entirely, which it can. You can get endometriosis in the diaphragm, in the thorax, in the lungs uh huh. So this menstrual backwash theory doesn't quite some work, need some work, or it just.

multicellular human, our cells are differentiating. They're becoming like grown up quote unquote grown up cells that have a specific job and function well. Stem cells are kind of like baby cells that have the ability to grow up and be any other type of cell or many other types

of cells. So there's a theory that perhaps bone marrow stem cells, which have the ability to differentiate into a number of cell types, might somehow find their way into the peritoneum or the abdominal cavity, and then there they would embed and under certain hormonal influences would differentiate into endometrial cells for some reason.

into endometrial cells. So it's logical then that they would could be responsive to the same hormonal influences that they would if they were still in the inside of the uterus. Does that make sense?

abdominal cells wherever in your abdomen just undergo metaplasia. Metaplasia means they develop mutations and then they change and so instead of being a differentiated let's say, abdominal wall cell, they dedifferentiate and then redifferentiate into endometrial cells.

get endometriosis and others don't? Maybe it is one of these theories that we already have, Maybe it really is menstrual backwash, But it still doesn't answer the question of why forty percent of people have menstrual backwash and not forty percent of people have endometriosis? Right, right, And part of the answer to that question at least seems to

be genetic. So in a number of genome wide association studies, which is when you look at someone's entire genome and you try and figure out what's going on, there have been I think at least like ten or fifteen different gene low size, so different locations that have been shown to be associated with endometriosis. So we know that there's a strong genetic component, but knowing that there's at least ten or fifteen different genes is also maybe not all

that helpful because it's hard to know what that means. Right. It does seem like all of these gene regions are in some way related to hormonal regulation in some respect, so a lot of this is a hormonally driven disease and really an estrogen dependent disease in a lot of ways.

But really one of the prevailing thoughts is that it is this kind of genetic and epigenetic factors combined with these unknown environmental insults that leads to endometriosis, and endometriosis is associated with a number of other autoimmune disorders, and that's kind of the thinking with autoimmune disorders as well. Right, It's these genetic predispositions and some kind of environmental influences that combine together to then lead to this disease.

increased amounts of inflammation. And this we do know. So we know that local inflammation and immune dysregulation is a really big part of the pathogenicity of endometriosis, and this inflammation itself is what then leads to the fibrosis, which leads to these adhesions, which can lead to such signific pain and symptoms. So one way to think of it is that it's all related to the bleeding because endometral

proliferation and then degeneration leads to so much bleeding. The bleeding itself, like blood itself, is a very very inflammatory. So the fact that it's trapped somewhere inside your body rather than traveling through the vaginal canal leads to a lot of inflammation, which leads to immune cell infiltration, which et cetera, et cetera, all the way down the line. But it's also not clear that that's the order in

which things go. It could be that do you have underlying inflammatory changes, differences in the way that your inflammatory markers react that then leads to the increased inflammation. Does that make sense?

Use these superficial lesions, and they're generally small. I don't have an exact size for you, but they don't extend very deeply. That's the first type. Then there are ovarian endometriomas, which is where we got the name for our drink. This basically just means that the endometriosis has implanted on or within the ovary. It's actually thought that it might be like where the eggs pop out. If endometrill implants find their way in there, they then become enclosed and

then they form. They can form these really rather large cysts, and because they are enclosed within kind of ovarian tissue and scar tissue around them, they undergo the same cycles of proliferation and degeneration, and within time that blood is like contained inside this cyst, and over time that be comes a very dark like chocolate color, which is how they got the name chocolate cysts.

your urytor for example. God, yeah, it can be horrific, and so especially deeply infiltrating endometriosis can cause not only incredible pain, but also can then cause damage to and blockage of really important structures like your colon or your bladder or your urtors.

very problematic. But of course the deeply infiltrating endometriosis has the most potential to cause problems in other organs, for example. But in terms of pain, which is kind of the biggest symptom of endometriosis, any of the types can cause pain, or any of the types might not be associated with pain,

So in that respect, it's difficult. In terms of pain, Aaron, Yeah, So pain is classically like the hallmark symptom I guess of endometriosis, and most classically it's dysmenorrhea, which is painful periods, which sounds like h that doesn't everyone have painful periods? This is not so period pain typical period. Pain should not be so bad that you are missing school, that you are missing work, that you are laid out in your bed for an entire week because you can't function

as a human being. And that's the kind of pain that is often associated with endometriosis. You're not able to function because of how much pain is associated with it. But it's not just with menstruation, especially as these endometrial implants sort of just persist over time. It can also be dysperunea, which is pain with penetrative sex, which can be hugely impactful on somebody's life, pain with defecation, dyskesia,

painful urination, just pain, pain with everything, pain all the time, chronically. So, but here's the thing about pain. I'm probably not going to do this justice, but i want to just briefly talk about the like neurobiology of pain. If we have time, let's do it long episodes.

that I think are really important to kind of understand. First, FIR studies have found that endometriotic implants, this endometriosis in your abdomen, often has higher densities of nerve fibers, so they're more densely enervated than the surrounding tissue. They're also more highly sensitized, so they actually respond at a lower threshold of stimuli, which leads to both of those things combined lead to an increase in pain signal transmission to the brain.

very painful periods. People who have chronic pelvic pain have a lower peripheral input at which they experience pain and a higher activity higher activation of their central nervous system in response to that pain. They are literally primed by experiencing chronic pain to then experience more pain.

And again here we don't know why. Huh really, yeah, we don't know if it's because of scar tissue that can form, especially if it's from endometriomas on the ovary like scarring the ovary or disrupting the number of ovarian follicles that you have left, or if it can cause scarring in the Filippian tubes, or there's some thought that it's just from how much inflammation exists in the pelvis because of endometriosis, because again it's an open cavity between

your ovary and your Filippian tubes, so small space, but it's all bathed in the same fluid. And so if that fluid is full of inflammation, then how is that egg supposed to make it safely into the uterus? Right, So we don't really know the mechanisms, but endometriosis is strongly associated with difficulty either getting pregnant or carrying a

pregnancy to term, but especially in getting pregnant. And let's talk about something that can have a huge impact on your mental and emotional well being, especially in a society that often ties a uterus holder's worth to their ability to conceive. Like, that's not small potatoes. That's a big deal, right, yep, yeah it is. What else do you want to know about endometriosiserin because that was a lot.

skin changes, acne, mood changes. These can also affect your bone mineralization and bone density, so they put you at risk for like osteoporosis. And even these don't always work, So then there's surgery, and surgery sometimes is still cited as the kind of gold standard or the only quote real way whatever to diagnose endometriosis. Yeah, the trend is moving away from that, thankfully, Okay, Okay.

was from surgery. But now we have other methods of being able to identify it, not only just with like clinical history, but also with imaging modalities like MRI and ultrasound, which can help to identify some kinds of endometriosis. But

surgery is often also seen as a treatment option. So ablation or excision of the endometriolesians can help improve pain for a lot of people, but it can also in some cases create more inflammation and more adhesions, which can then exacerbate symptoms or possibly even lead to more endometriosis lesions. If we think that it's inflammation that's the driver rather than vice versa.

especially chronic pain. We don't have a lot of good options for it, so that part of endometriosis is very difficult. If these other therapies aren't effective. So it's a bummer Erin.

from getting the healthcare they need and deserve. So that's what I'm going to talk a lot about today. Good, and before I dive in, I want to briefly discuss the language I'll be using. The story of endometriosis involves aspects of both sex aka common biological differences between males and females, as well as gender aka the socially constructed roles that vary between gender as that people identify with. And as you mentioned, Aaron, endometriosis can affect people who

don't identify as women. It can affect people assign female, male, or intersex at birth, and its label as a female only or women's disease can be very damaging and can delay diagnosis even further for those that don't fit the description of a typical ENDO patient, whatever that means. But much of what I'll be talking about today is a gendered issue. It has to do with the way that women are perceived in medicine and how that impacts their treatment.

The fact that endometriosis primarily occurs in people assigned female at birth has given rise to many of the social issues and medical disparities surrounding endometriosis. Many of these issues, such as how people experiencing pain are perceived by medical providers, are discussed in the literature and in scientific studies using the terms men and women without saying whether they mean sex or gender, but generally we're speaking referred to cisgender people.

This is definitely a huge limitation of these studies and of this discussion as well, especially since there are many ways that trans or gender non binary people are treated differently than CIS people in medicine, often in ways that negatively impact their health. And I'm going to try my best to be inclusive and not to ignore the experiences of those people or exclude them from this history. But studies examining those aspects are scarcer, Yeah.

and environmental factors. And it seems like in the case of endometriosis, I've read that it's about fifty percent genes and fifty percent environmental factors.

Like I've seen estimates from ten to fifteen percent, and those frankly seem like they could be conservative estimates or underestimates, because I'm sure many people with endometriosis never get a diagnosis for any number of reasons, such as whether they can afford to see a doctor, to take time off work and find reliable transport to a doctor, or even if they can see a doctor, maybe they're just dismissed or called dramatic, or maybe they just don't know that

debilitating periods aren't normal because periods are a taboo discussion topic.

your genes determining whether or not you get endometriosis. It's also environmental factors. And it turns out that endometriosis might not deserve the reputation it has for causing infertility. So it seems like in a lot of the literature and estimate around thirty percent is often reported, but more recent studies put it actually lower at about ten to thirteen percent.

endometriosis and polycystic ovarian syndrome are opposites. Did you know this paper?

are brought to their extremes. And the way that I started thinking about this was like too much of a good thing. So individually, these traits might be helpful for fertility, but when you have too many of those traits or

they are expressed too highly, it can be hurtful. So something like uterine contractions, it's great for when you have fetus with a big head in there, but horrible for when you have menstrual cramps that lay you flat, or like inflammation right, high level like inflammation is good, it helped what keeps us healthy. To high levels of inflammation

can be really, really bad. So taking all that together, I feel like we can start to see why endometriosis exists and why we see it in fairly prevalent numbers today. So my next question is do we have more endo today than we've had in the past. How long has endometriosis been around. Endometriosis often gets called a modern disease or a modern epidemic. Did you come across papers describing it that way?

is untrue. Humans have probably been experiencing endometriosis for millennia, as I'll get into and some people who defend the use of the term modern to describe endometriosis say that it's because it was only defined as a clinical entity within the past one hundred to one hundred and fifty years, and that definitive diagnosis by examining tissue under a microscope

was only possible in the last one hundred years. So despite the existence of ancient medical texts describing abnormal bleeding associated with pelvic pain and infertility, those descriptions apparently aren't specific enough to be called endometriosis, which I'll grant is fair. Retrospective diagnosis is always a problem.

out why. But endometriosis is an ancient disease. There are descriptions of painful menstruation which could be endo, dating back to eighteen fifty five BCE from ancient Egypt, and then again in ancient Greece in the Hippocratic text from the fifth and fourth centuries BCE, describing menstrual dysfunction as a cause of disease, with pain and infertility resulting if left untreated, and pregnancy as a possible cure, which, despite not being

true not being a cure, is often still reckon mended today. In fact, I read in one book, uh for this episode, that somebody commented on a Facebook page for a group called endoactive about this quote. My doctor told me having a baby would help my pain. I'm only eleven. What uh huh yeah, oh no, mm hmm oh no erin yeah, I've been mad for the fast time I've been researching this.

so many people who were diagnosed with hysteria probably had endo. Anyway, from those ancient texts describe be pain during menstruation and abnormal periods, there doesn't really seem to be a ton of other mentions of what could be endometriosis, not because people weren't experiencing it, but likely because there was and still is a huge taboo surrounding menstruation from Leviticus in the Old Testament quote if a woman has a discharge, and the discharge from her body is blood, she shall

be set apart seven days, and whoever touches her shall be unclean until evening. Fast forward to the first time that the word period was said on television like you know, like menstrual period nineteen eighty five, no way, by Courtney Cox in a tampon commercial.

the experiences of others. Right, The persistent labeling of menstrual periods as a distasteful and shameful subject has profound implications for public health, and it creates enormous inequities for people who menstruate. In most states, tampons, for example, are subject to sales tax, and also in most states, prisons charge inmates for menstrual products. I know, there's just so much,

so much, there's so much. But circling back to the history part of this, maybe the reason that endometriosis doesn't show up very much until basically the eighteen hundreds is because the people writing medical texts were primarily men, most of whom would have considered it deeply improper and probably

gross to ask a woman about her periods. It's absolutely possible and likely that women discuss periods amongst themselves, and there was probably a great deal of knowledge held by women healers, which was mostly lost as medical licensing laws came into effect, which both prohibited them from practicing reasonable licenses are good and even applying to medical school. If you weren't a white wealthy man, you weren't getting in.

But with the increasing popularity of autopsies in the nineteenth century, people begin linking more and more signs and symptoms of disease with pathological changes in the body. Karl Vaughan Rokotansky, whose name you may remember from our pupil Fever episode.

And there was a series of autopsy studies done by other physicians from England, Germany, Holland and Scotland also in the eighteen hundreds that went further than Rokatansky to characterize the disease, but it wasn't until nineteen twenty one that It was given the name endemtri triosis by John Sampson, who is an American gynecologist who also did the first systematic study of the disease and proposed a hypothesis that is still the most popular today, the menstrual backwash hypothesis.

The papers published by Samson marked a turning point in the history of endometriosis. They turned it from a medical curiosity into a clinical entity, and now that it had a name, it meant that information could be compiled and shared under that name. Receiving a diagnosis itself didn't do much good, similar to today, in many cases and often did harm because, like you said, Aaron, usually a complete removal of the uterus was suggested as the only effective treatment.

A couple of decades after Samson's papers, endometriosis of the lungs, large bowel, colon, rectum, bladder, lymph node, cervix, round ligaments, and so on had been reported, and physicians began to realize that it was a lot more prevalent than Samson had thought, who described it as a rare disease. Laparoscopic surgery began to be more regularly used for the removal of lesions starting in around the late nineteen seventies early nineteen eighties. But frankly, is as you went over, not

a whole lot of progress seems to have been made since. Like, yes, we know more about endometriosis now than we did one hundred years ago, but we're still limited in treatment and hugely lacking in awareness among both medical professionals as well as the general public, which has led in part to the ridiculous delay in endometriosis diagnosis. I mean, I've seen estimates of six to twelve years.

do some people get it and others don't? And exploring those questions kind of led me into reading more generally about the pervasive mistreatment and under treatment of women by the medical system. Right off the bat, I want to mention the books that I read for this because I'll probably be quoting from them a lot, one in particular, and they are phenomenal and I learned so much and

got so angry along the way. Doing Harm by Maya duson Berry and Pain and Prejudice by Gabrielle Jackson are both nonfiction books about the systemic issues in medicine and how women are treated. Ask Me About My Uterus by Abbie Norman and Giving Up the Ghost by Hillary Mantel are memoirs about endometriosis. Hillary Mantel's book includes a section on her experience with enemetriosis. It's not entirely about ENDO. I loved them all and you should read them all, Okay.

So the way that I wanted to structure this discussion is taken directly from Maya Dusenberry's Doing Harm. In this incredible book, she lays out what she calls the knowledge

gap and the trust gap. The knowledge gap is basically that there isn't as much scientific and medical knowledge about women's bodies and health issues than there is about men's and this goes all the way from the very basic biomedical research only including male animals and studies all the way to women being underrepresented in clinical trials and diseases specific to women receiving less funding. The trust gap is simply that quote women's accounts of their symptoms are too

often not believed. The trust gap and the knowledge gap don't operate independently. They reinforce each other to perpetuate the mistreatment and under treatment of women by the medical system. Quote from Dusomberry. Women's symptoms are not taken seriously because medicine doesn't know as much about their bodies and health problems. And medicine doesn't know as much about their bodies and health problems because it doesn't take their symptoms seriously. End quote.

Dousomberry points out that these issues aren't about a few bad apples in the medical system mistreating women, but rather the unconscious bias that is structurally embedded in medicine. So let's explore these two facets in a bit more depth, starting with the knowledge gap. As with any structurally embedded issue, we discuss the podcast. The knowledge gap has deep roots, stemming from the hundreds of years during which women were seen as biologically inferior to men and whose bodies were

either not worthy of study or improper to examine. And if they were studied, for instance, by the so called father of gynecology, Mary and Simms, who built the profession on the backs of enslaved women, they were essentially tortured, given no anesthesia or pain relief, seen to be subhuman. The ideal baseline that defined what was medically quote normal or human was a white adult male, and let's be honest,

a wealthy one. This is pretty clear when we look at how menstrual periods were described in medical texts throughout the eighteen hundreds as times of ill health. Anytime a woman was either pregnant, menstruating, or in menopause, she was considered unwell and her thoughts scattered and disturbed, which was used in arguments against women being allowed to attend universities and higher education. Anyway was thought to atrophy the uterus.

color from practicing medicine and contributing to the field. Those that remained were white, wealthy men, and so a white male as the baseline for comparison, and the health ideal became entrenched in medical training and medical knowledge well into the twentieth century. The nineteen sixties and nineteen seventies saw a great deal of change in terms of medical ethics, as things like Tuskegee and tholidamide revealed the enormous failings

of informed consent and protections for vulnerable individuals. Many of these developments in drug safety studies were overwhelmingly positive in terms of preventing people from being coerced into unsafe studies and being harmed, But one unintended consequence was when protection turned paternalistic, essentially preventing women from being included in drug trials simply because they were women, or, more specifically, in the nineteen seventy seven FDA policy excluding women of quote

child bearing potential from early phase drug studies. This meant anyone who potentially could get pregnant.

is safe or effective for them? This is especially problematic and tricky in terms of pregnant people, where it's kind of like a rock and a hard placed situation, basically forcing a choice between including pregnant people in clinical trials which could put the fetus and the person at risk, or in effect testing it out on them later in an uncontrolled fashion, hoping that the studies showing it safe in people who are not pregnant will mean that it's

safe for pregnant people. It's complicated, and I'm not going to go into it here because I just don't have the background knowledge to do so. But one thing that does seem to be clear is that there is underrepresentation of women and pregnant people in clinical trials.

exclude them? And the answer to all of these here's another quote, And I just I should say that unless I say differently, these quotes are from doing harm by Maya Dusonberry quote. In short, studying only one sex was cheaper and easier, and men were the chosen ones because women's bodies were thought to be too complicated.

research to light. At this time, a group of scientists who were women formed what is now known as the Society for the Advancement of Women's Health Research, and they demanded an audit by the Government Accounting Office the GOAO of the NIH's research efforts to see how well they had stuck to the nineteen eighty five Policy for the Inclusion of Women in research. This GOAO report, which was

published in nineteen ninety, was staggering. They had done next to nothing in most of the studies that the NIH funded. They couldn't say what other women were included, or if they were how many. So far, I've talked about this more generally right, more and more descriptive, abstract women are excluded from studies. So let's get into some more solid

examples that illustrate the knowledge gap. For example, there's a famous study called the Baltimore Longitudinal Study of Aging that was started in nineteen fifty eight and aimed to study quote, normal human aging. This was the one that found that a baby aspirin a day could be protective against heart disease. You know that, Like, now that's conventional wisdom or whatever. Yeah, that study didn't include women, included thousands of men. It

didn't include women for twenty years. Another large scale study started in nineteen eighty two, whose aim was to study the effects of dietary change and exercise on heart disease, included thirteen thousand men and zero men, despite the fact that heart disease is and was then one of the leading causes of death in women. And then there's this I think it takes the cake quota directly again from doing harm by Maya Dusonberry. There's a quote and then

a quote within a quote. So the inception of quotes quote and nih supported pilot study from Rockefeller University that looked at how obesity affected breast and uterine cancer didn't enroll a single woman.

inclusion of women and enormous consequences because of that. Biological differences between people assigned male at birth and people assigned female at birth have historically been used to claim inferiority or superiority while failing to examine the potential health impact of that difference, such as in the way drugs are metabolized, which is impacted by fat distribution and hormones, among other factors.

So when women aren't included in drug trials, should we be surprised by the finding that women are quote fifty to seventy five percent more likely than men to have an adverse drug reaction. Like, that's not a surprising finding, it's horrible.

gender or whatever these pain differences. There was a study from two thousand and five that found that almost eighty percent of animal pain studies used male animals only. And while the lack of sex analysis in animal studies of all kinds is hugely problematic, it really only captures one aspect of the knowledge gap. These studies don't take into account the gender bias and social factors that influence health

and are hugely important to examine. The nineteen ninety GAO Report did change some things for the better, but were still not even close to equitable, and many studies simply failed to report any sex or gender analysis of results. There have been suggestions to require the inclusion of such analysis for publication in peer reviewed journals, but that has been met with some resistance for vague scientific reasons, whatever

that means. But still, even though things are getting better, there is a huge lag time in between and when those studies are conducted to when the results are analyzed and published, to when it becomes presented to the interested field, to then the wider community, to then when it becomes included in textbooks, to then when it trickles out to the rest of the public. Let's illustrate picture someone having a heart attack. Okay, what do they look like? What

are they doing? What are those signs and symptoms they seem to be feeling.

There's a lot of studies in hospitals, like the time from into the emergency room to treatment and like into the or it's super short ovaryan torsion.

Medical doctors only know what heart attacks look like in men, and they are disinclined to believe that women's symptoms are real. So now let's get into the trust gap. If you thought the knowledge gap had deep roots, wait until you hear about the trust gap. In order to explain these roots, I'm going to take us through a brief history of hysteria, which was first described in ancient Egypt and got its name from ancient Greece. Like I said, from the Greek

word for uterus histra, what is hysteria. It's basically the idea that a woman's health and mental status is tied directly to her utter and that all disease in a woman came from the uterus wandering around the body like literally wandering, but just like these restless uteri. The definition

of hysteria has also wandered substantially throughout history. In ancient Greece, in Hippocratic texts from around the fifth century BCE, it seemed to be thought of as an organic biological process, one which was likely to happen if marriage was put off for too long or if a woman didn't get

pregnant early enough after puberty. In Europe and the centuries after, throughout the medieval period, the meaning changed and became more spiritually based, and it was thought that the uterus could be inhabited by a demon or evil spirits, or possessed via witchcraft. And the uterus became the scapegoat for any disease or complaint that a woman had. In hysteria, the catch all diagnosis.

body temperature, etc. All these things. I think in our sickle cell episode, I talked about how these tools, in addition to medical specialization, led to medicine shifting to be less about the person and more about the body or a part of the body. It also led to this important distinction between signs and symptoms. Signs being something that someone who is not the patient can measure or see or feel. Symptoms are the things that only the patient

can feel and describe. Signs are objective, symptoms subjective. As the ability to detect disease signs became more refined, diagnosis increasingly relied on signs rather than symptoms, and a physician could listen less or not at all to their patient and still end up successfully treating them, offering a not so great precedent. But it also meant that if there were no signs or the signs didn't tell them anything, they could and often did, disregard the symptoms as hysterical.

In of the eighteen hundreds, Jean Martin Charcot tried to reclassify hysteria as a neurological disorder rather than a personality flaw, believing that believing that the ovaries, rather than the uterus, diverted energy from the brain during menstruation, pregnancy, lactation, menopause, ovulation, et cetera, and that the brain, drained of all this energy, could barely function and left women weak.

seventy percent were in like the mid eighteen hundreds. I'm not going to get into Charco's ovary presser, but suffice it to say that he carried out extensive medicalized torture on women and asylums to try to confirm his ideas about hysteria from a wandering uterus to demonic possession to a neurological disease. Hysteria had one more major transformation to undergo, and it was this final one that left such an enduring mark on how women are perceived in medicine today.

to do all of this. So Freud initially jumped on the charcot of hysteria as a neurological disorder, but then changed his mind, turning it into a disease that was entirely psychological, often attributed to the underdevelopment of libido or sexuality, or the rejection of feminine values or feminine traits, cured

through talk therapy. What this did was turn real things that women were experiencing, pain, fatigue, heavy or irregular periods, infertility, even into something that she was doing with her mind. It's all in your head. This probably sounds familiar to many people listening today who have maybe been told something similar by a doctor they thought they could trust. To listen, because despite how this story is sometimes told, hysteria didn't

disappear after Freud. It may have fallen out of fashion and lost credibility as a medical diet dignosis a bit. But number one, it wasn't actually removed from the DSM, the Diagnostic and Statistical Manual of Mental Disorders until nineteen eighty and number two, it never really went away, but was rather repackaged. Out of this umbrella term hysteria came endometriosis, MS, chronic pelvic pain, many autoimmune diseases, samatitization, psychogenic illness, medically

unexplained symptoms, so many things. Freud's transformation of hysteria into a psychological disorder turned women into unreliable sources on their own body. Essentially, a woman is thought to be lying about her symptoms unless there is observable proof to the contrary, or her symptoms are real but psychogenic unless you can

prove otherwise. A gynecology textbook from nineteen seventy one said that quote many women wittingly or unwittingly exaggerate the severity of their complaints to gratify neurotic desires end quote, and in the same textbook that morning sickness quote may indicate resentment, ambivalence, and inadequacy in women ill prepared for motherhood. Ooh as if you needed more things to get angry about.

as crazy. One proponent of psychogenic diagnoses says that quote the vehemence with which many patients insist their illness is medical rather than psychiatric, has become one of the hallmarks of the conditions. So like, the more you say no, this is a real pain, the more likely you are to be diagnosed with the psychogenic illness.

to the description quote. Only fifteen percent of medical students or residents diagnosed heart disease in the woman, compared to fifty six percent for the man, and only thirty percent referred the woman to a cardiologist compared to sixty two percent for the man that quotes from pain and prejudice. The explanation given for the woman's symptoms turned from biological to psychological, and there was no difference in the results

based on the gender of the doctors. It seems that too often when physicians meet with the patient, they see the diagnosis in the identity of the patient based on implicit biases built into the medical training system. If you're a woman, it's in your head or your uterus. If you're a black person, you're drug seeking. If you're trans and you're on hormone therapy, it's because of the hormones. If you're fat, it's because you need to lose weight.

If you've ever been diagnosed with anxiety or depression, clearly that's what's causing your pelvic pain or your chronic fatigue. It's rarely that endometriosis could be a source of anxiety or depression, right instead of depression causing your pelvic pain. This anecdote paraphrased from doing harm. There was an eleven year old girl who had severe abdominal pain and nausea. She went to the er. The doctor told her it was menstrual cramps, despite the fact that she had not

yet gotten her period. Ever, the pain didn't go away, so the next day, in agony, she had to be rushed back to the er, and at this point her mom, who was a physician, demanded an ultrasound, and they found the largest unruptured appendix that the surgeon had ever removed. Would that have happened if it had been eleven year old boy instead of an eleven year old girl?

are inadequate at describing and measuring pain. I mean absolutely inadequate. These women, these mystery women, are often a source of frustration for physicians, and they're dismissively called malingerers, never wells et cetera. Concern turns to resentment as nothing seems to work and the answer to the problem seems forever out of reach. I can't see anything wrong with you, so there must not be anything wrong with you. A physician sense of self worth shouldn't be tied up in having

an answer or the right answer. There's an incredible power in empathy in saying I don't know, but let's find out. So where does that all leave us with endometriosis. We have come a long way since the early days of hysteria and endometriosis, and the people who have made the biggest strides in raising awareness of endometriosis are patient advocacy groups, people who have had to become experts in a disease that their own physicians often failed to communicate with them about.

But we haven't come nearly far enough. Stereotypes about endometriosis have persisted long after being disproven, such as endometriosis is rare in women of color or only happens to women

who put off marriage and childbearing. These stereotypes, combined with the outrageous lack of knowledge about how endometriosis actually works, and the tendency for physicians to dismiss or downplay the pain experienced by women, these all contribute to the long, often excruciating years people have to wait for a diagnosis, and still endometriosis is too often made to be about

a woman's social or gender role. Endometriosis can absolutely impact a person's fertility, and for someone who wants or thinks they might want to have children, that's hugely important. But often fertility is preserved as a default without asking the patient whether or not subfertility or infertility would be acceptable

if it meant reducing the pain. Yea and A two thousand and three study found that women who sought out doctors because of infertility received a diagnosis of endometriosis in half the time that women complaining of menstrual pain did.

Are there any things that you do that you help your period and make you feel better? Like all these things so important?

close it at all. But it shouldn't be unreasonable to expect that during this period of uncertainty, the benefit of the doubt be given to the patient. The default assumption be that their symptoms are real, their description of what they are feeling in their own bodies be believed, and if it is medically unexplained, the burden be on medicine to explain it. Such basic trust has been denied to women for far too long end quote. So erin, I

have a feeling I might just get angrier. But can you tell me where we stand with endometrios's today?

are not child bearing age can have endometriosis. Lots of people with the uterus that aren't women of child bearing age can have endometriosis. And so does that ten percent actually mean like ten percent of people with a uterus have endometriosis? Or is that number higher because people with the uterus maybe had entometriosis when they were younger, and now they're older, the symptoms have gone away, but those people still count, right, So I don't have an answer for you.

let's compare that, Aaron, you mentioned diabetes. Almost used that. But let's talk about breast cancer, shall we. Thirteen percent of women in the US will develop breast cancer. Thirteen percent. That's really close to ten percent. We have a whole month dedicated to breast cancer, don't we.

think this is now my soapbox. This is for a lot of reasons that Aaron, you really kind of focused on so many of them, and if we really drill down to it, like it comes back to the patriarchy, as it always does, but at its core, it also is because I think endometriosis is classified in all of the literature as a quote benign condition. What So, endometriosis is classified as a quote benign condition.

in a way right. It can be found well outside the peritoneal cavity, and by definition it is tissue found outside where it's supposed to be. And in the case of deeply infiltrating endometriosis, it does invade deeper tissues in the same way that cancer can. But endometriosis causes pain, causes suffering, causes infertility, and that, my friends, is seen as benign. It can in made your bowels and cause obstruction, but it usually doesn't. That's uncommon. It can invade your

bladder or your urroters and cause obstruction. It can cause destruction of your urrotors, but it doesn't often. And because it's a histologically recognizable tissue type, and because it generally quote unquote doesn't invade to the extent that a cancer would, and because it generally subsides after menopause, after the withdrawal of those hormones, it is quote benign. Okay, it's clearly nothing of the.

higher than in people without endometriosis. So even though endometriosis itself is not a cancerous condition, it's not without its risks. Yeah, right, I mean, so far as that goes ah, isn't that just fascinating?

and it doesn't fit the definition of a cancer. There have been a number of new mutations identified in endometrial tissue that are associated with cancer, but never enough of them, like only one mutation instead of three mutations that would then cause it to be a cancer. So it is not a cancer, and it does not metastasize the way that a cancer does. But it's not normal tissue either. So it's an interesting disease in that respect, and we

have a long way to go to understanding it. I was thinking this and feeling this, and then I went for a walk today and I was listening to an episode of Vox's podcast Unexplainable, and they have an episode on endometriosis. It's really great. It has stories from like fourteen people who have been living with endometriosis. I recommend the listen. But they also had an interview with someone who researches endometri it's doctor Lisa Griffiths. She is at

MIT and runs the Center for Gynopathology Research. Her research is super fascinating. Its focuses on tissue engineering, like growing endometrial tissue on like chips, and they're trying to develop better diagnostic markers that can be used to not only diagnose, but then also classify endometriosis into different subtypes, which could then theoretically lead to more personalized or targeted treatment options,

which is amazing. But she also brought up this exact same thing that like, the language that we use surrounding endometriosis is so important, and she was saying that, like her collaborators kept calling it a benign condition, benign condition, and she was like, I live with this, she has endometriosis. She's like, there's nothing benign about it. Yeah, right, But it's that difference between quote medical language and colloquial language, right.

But it matters, right, and it influences we are all humans, even in the medical community. It influences the way that we perceive it and then the way that we treat people who are living with it. There are a lot of people doing research on endometriosis from so many different angles because there's so much that we don't know. So I already mentioned some fascinating research by the Center for

Gynopathology Research. There's also other groups like Citizen Endo, which is led by doctor Noemi Elhadad at Columbia University and their team. Super fascinating are using like citizen science y based tools to try and better characterize the symptoms of endometriosis to try and bridge the gaps between what clinicians know or think they know or think about endometriosis and how people who are living with it actually experience endometriosis, which I love so much.

of the evolutionary biology. Those papers that I mentioned are both by Dinsdale at All from twenty twenty one.

we know about the mechanisms of endometriosis. I think my favorite one was from Nature Reviews Enderchronology in twenty nineteen, as well as another one in the Annual Review of Pathology Mechanisms of Disease from twenty twenty. We'll post all of these sources from this episode and every one of our now eighty eight episodes.