The bleeding edge, part two

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Hi, hello, nice to meet you.

I'm Bird.

A few months ago, I visited the Feinstein Institutes for Medical Research on Long Island.

I was there because I wanted to see something called the Rose Study and to meet people like Amber Laguerre.

So I wanted to just introduce myself.

So I'm one of the coordinators for the study.

So I speak to all of the participants from enrollment to consenting to sample collection and everything in between.

The samples that Amber mentioned are samples of menstrual fluid.

So participants in the study use cups or special pads to collect their fluid, and then they ship it to this lab in special mailing boxes.

And I had timed my visit to see one of those boxes come in.

So, I actually wanted to show you, we received a kit earlier this morning.

If you'd like to see one, if that's okay.

No, actually,

okay, that's kind of a lot.

That's fine.

So, no, I would love to see this.

Do you?

Because it's okay.

No, I was just kidding.

Okay, we're just kidding.

I really was just trying to make a silly throwaway joke here, like the kind of thing that sometimes loosens people up a little bit.

I had traveled over an hour on trains and buses to see this sample, and I thought it'd be really obvious that I was excited and just kind of goofing around.

But instead, both Amber and one of the directors of the study, this woman named Christine Metz,

both of them took me completely at my word here and also took a lot of pains to acknowledge that any feelings that I might have about menstrual fluid were perfectly valid.

We have responses of all kinds and we accept responses of all kinds.

Nothing is weird here at this point.

These are all very normal things.

So we're very open about, you know, like showing it and talking about it.

Oh, of course.

No, like I.

It's okay.

It's a lot.

But what was I saying?

Amber very quickly moved on and pulled over this cardboard shipping box to show me.

Everyone receives a kit like this, an insulated box.

But as she pulled out the sort of tube full of raspberry red liquid that I had come to see.

And it's a pretty great sample.

There's a few small clots in there.

I couldn't stop thinking about my glib little joke and her very calm reaction to it.

I really was pretty comfortable with this vial of menstrual fluid.

Like, I'm not a particularly squeamish person.

And also, I was there for work.

So their reactions surprised me.

Like, if anything, I assumed they would be desensitized to the taboos around menstrual fluid.

But their kind of careful consideration of my feelings, it made me realize just how much stigma there still is around menstrual fluid, but also how much researchers still have to wrestle with that stigma.

So, this is Unexplainable.

I'm Bert Pinkerton, and this is the second episode of our series, The Bleeding Edge.

This week, we're looking at the scientists at the Rose Study who are collecting these vials of menstrual fluid because they want to to figure out if menstrual fluid could be used to detect a widespread and painful disease called endometriosis.

It's a pretty fascinating idea and could potentially help millions of people, but it's been challenging because from the very beginning, the stigma around menstrual fluid has shaped the work that these researchers do.

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For Christine Metz, this whole project started about a decade ago.

I had been working in the area of endometriosis and studying inflammation related to endometriosis.

Endometriosis is a disease where tissue that's a lot like the tissue that grows inside the uterus starts growing in other parts of the body instead.

And that can be extremely painful, like in some cases so painful that it severely impacts what patients are able to do or how they're able to live their lives.

And it's also surprisingly common.

It's a condition that affects one in 10 menstruators.

That's millions and millions of people overall.

And so Christine started talking about endo with one of her colleagues, a geneticist named Peter Gregerson.

And he was interested because a friend of his was one of the millions of patients who has it, and also because the disease just seemed like it was up his scientific alley.

It is highly genetic,

which initially attracted me.

And so that allowed us to get together to really look at this disease from several different vantage points.

Christine and Peter got to talking about how hard it is to diagnose the disease.

The statistics suggest that it's about seven to 10 years between symptoms and an actual laparoscopic surgical diagnosis, which is the only definitive way to diagnose endometriosis.

Basically, surgeons have to go in and find endometriosis lesions to confirm an endodiagnosis.

But because surgery is a big, often expensive step, people sometimes put it off for a while.

And then without a diagnosis, doctors can dismiss people's pain.

Like they sometimes suggest that patients are exaggerating or that they just have a low pain threshold and then send them on their way.

And we thought, wow, that's crazy.

You know, how can we continue to have people suffering without a diagnosis?

But as Christine and Peter sort of talk some more,

they came up with the idea that sort of at the heart of the Rose study.

They thought that endometriosis might have kind of a cellular signature, basically, like a pattern of cells or cell behavior that could tell you this is endometriosis without someone needing to go in and find lesions.

And there was some literature to support this.

Like some scientists had looked at tissue from endometriosis patients' uteruses, and they'd noticed that some of the cells of endo patients were different from the cells of patients without endo.

So, Christine and Peter obviously wanted to investigate this further, except there was a problem.

Most of the studies of the uterine lining are based on uterine biopsies.

Which require invasive procedures.

So, not something that a patient or a research volunteer can do casually.

There's got to be a better way of characterizing what the uterine lining looks like without having to subject them to biopsies.

So, that's how Christine and Peter landed on menstrual fluid.

Most people think of their menstrual blood as something that gets discarded, and that's how it has been viewed, something that should be discarded.

But in fact, we believe that it's a window into studying and understanding the uterus, and that it's certainly a treasure, not trash, and that it holds a lot of information.

It seems almost obvious.

Like people with uteruses shed their uterine lining approximately once a month.

So instead of going in there surgically to grab the lining, why not just wait for the uterine lining to come to you?

But apparently, this was not all that obvious.

We were kind of shocked because the uterus has been identified for a very long time,

yet to understand the uterus, no one has said, oh, well, we could study menstrual blood.

And it was a shocking revelation.

We went to the literature like everybody else as a scientist would do,

and we were shocked to see that there were

very few studies that ever looked at menstrual blood, collected menstrual blood, and actually characterized it in any way other than the identification of stem cells.

I mean, there's standard ways to collect stools, there's standard ways to collect urine and semen, but no one has really thought about collecting menstrual blood in a consistent way that would be consistent with scientific studies.

This might seem like a small thing, but science is sort of like trying to cut a trail through the woods.

When lots of people have studied something before you, they clear the way a little bit.

Like they outline best practices so you can sort of follow in their footsteps for a while before you have to start cutting your own path.

But because there was so little prior work done on menstrual fluid, Christine and Peter couldn't just jump right in and start answering their main question.

Instead, they had to figure out not just how to collect menstrual fluid, but how to collect fluid from patients with endometriosis.

We took it really, really seriously because we knew that we wanted to collect eventually from young teens and people with pelvic pain and it had to be something that was usable

and feasible for them.

They also wanted to collect fluid from people who lived all over North America, which meant that there were more questions to answer.

How quickly do they have to get it to you?

Does it have to be on ice?

Does it get infected with things on the way being shipped here?

We did a lot of work.

Even once they had their samples, it took them a while to figure out which parts of the samples to focus on.

We didn't even look at the tissue fragments in menstrual blood for several years.

We threw them out.

Yeah, until it took working with the pathologist to just look at menstrual blood and see, hey, there are all these big clumps of tissues here.

Why aren't we studying those?

And all this trial and error and sort of like forging a path through the woods did not end with just sort of the technical challenges here.

What was the response of my research nurses to the idea that we now needed to collect menstrual blood?

They thought I was crazy.

They thought we were crazy.

You know, I mean, it took a while just to convert our own staff, who are very open-minded, wonderful people, that, oh, maybe this really is worth doing.

So we did succeed in doing that.

Now, of course, they have Amber, who first showed me that raspberry red vial of fluid and was very patient with me.

And they also have lots of other people working on this study, too.

So I'm going to take this to the biorepository and Loriana and Rixie are going to accession the sample and then it's all on the lab to do the rest.

After years of work, Christine and Peter have cleared enough of their scientific trail that they're ready to start answering their original questions.

After the break.

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You know, I've often wondered why it is that some women still call menstruation the curse.

Teggy calls it that.

And it is kind of a nuisance, isn't it?

I suppose it is sometimes.

After a lot of trial and error, Peter Gregerson and Christine Metz collected thousands of samples of menstrual fluid from donors.

So samples from participants diagnosed with endo, samples from participants with symptoms but no diagnosis, and then samples from participants who did not have the disease.

which meant that they could finally examine those samples to see if they could spot some sort of differences between them, some kind of like signature or pattern that was unique to endometriosis patients.

And each sample is really complex.

There are hundreds of thousands or even millions of cells in there.

So for each one, they examined just thousands of cells.

And what did we find?

They found exactly what they were looking for.

So more of one type of cell that's linked to inflammation, less of another type of cell that's connected to the immune system, patterns and how sort of cells changed into other cells.

And all of this taken together amounts to a kind of signature that endometriosis leaves in menstrual fluid, potentially.

They still need to make sure.

And so that's sort of what they're up to now.

We can definitively show the differences between patients who have been diagnosed with endometriosis and healthy controls.

We can clearly see those differences.

The next question to answer is, can we see

similar differences, or maybe there are unique differences in patients who are symptomatic and have not yet been diagnosed in healthy controls?

Remember, the goal is eventually to develop a test that could detect endometriosis using menstrual fluid so that patients don't have to undergo surgery.

And to achieve that goal, they need proof that their test actually works.

Like they need to look at fluid from patients who don't have a diagnosis yet, predict whether or not they have endo, and then confirm whether or not they were right using laparoscopic surgery.

So, this sounds very easy, right?

You get menstrual effluent a couple of months before they have laparoscopy.

Somebody goes in and says, Yep, there's endometriosis here, or no, there's no endometriosis here.

It is, as it turns out, not very easy.

I think the biggest challenge is finding

patients who want to undergo the diagnostic surgery to confirm their symptomatic state.

People do not jump into the surgery.

They often push it off for years.

But also, there's a chance of a false negative here.

So, like a situation where a surgeon goes in and says, I don't know, like, I don't see the right kind of lesions.

There is no endometriosis here, even when there actually is endometriosis there.

And because Christine and Peter's study sizes have been fairly small, one false negative could really mess things up.

You need to have a situation where the surgeon that is doing the evaluation is highly competent at saying, yes, there's endometriosis or no, there's no endometriosis.

So they are taking their time, kind of checking their work, confirming that this diagnostic test works.

But even then, their work won't be done.

Christine says that figuring out endometriosis's signature pattern could actually help with more than just diagnosis.

Because there's a lack of effective and tolerable treatments for patients with endometriosis.

One of the treatments out there is the pill, which helps some people, but not everyone.

Doctors can also try to remove endometriosis lesions by going in to surgically burn them or cut them.

And that does sometimes help, but the effects don't always last.

In our study, we have people who have had two surgeries, four surgeries, six surgeries, eight surgeries, 12 surgeries, 20 surgeries.

It can go on and on for some people.

Some people get hysterectomies, but even that doesn't always help.

The reason we don't have good treatments for this disease is that We don't understand what I'm going to call the biology of the disease.

We don't understand enough about the disease to have a better treatment than that.

And that's the big, you know, thrill of studying menstrual blood to us, in addition to diagnosing it, treating it.

The work that Christine and Peter are doing, it has the potential to help millions of people.

So if diagnosing and treating endometriosis was all menstrual fluid could do, that would already be a lot.

But then there's more.

Unfortunately, if you have a uterus, there are a lot of things that can go wrong with it, and can go wrong, and they often do.

Leah Hazard is a midwife and the author of Womb, the inside story of Where We All Began.

She has been digging into lots of research around menstrual fluid.

And it turns out that some scientists are starting to wonder about the scientific possibilities of menstrual fluid and uterine tissue.

Obviously, cancer is the big E, so there are people trying to predict or diagnose uterine cancer by studying the lining of the womb.

And we're also interested in maybe how the menstrual tissue of people with fibroids might differ from other people.

So, fibroids are benign growths within the uterus, so basically, benign tumors in a sense, but they can also cause pain and heavy bleeding.

And we've got adenomyosis, which is where the lining of the womb begins to burrow into the actual deeper muscle layer of the womb.

Tens of thousands of people have uterine cancer in the US, and tens of millions of people have fibroids.

That's why this research is so exciting.

There are

people now, more and more every year, who are taking the initiative and studying menstrual tissue and endometrial tissue to advance diagnosis and treatment of these conditions.

And yet, yet, the stigma that ruined my throwaway joke to Amber

is still very real.

Like, it's still subtly shaping this research.

It's hard to get funding for reproductive science.

And even if you do, there are all the hurdles that Christine and Peter had to clear, all the work that they had to do before they could start exploring their question.

It's like a shame tax is applied to menstruation research.

So,

as Leah Hazard put it to me, we don't have to love our periods or be period positive, right?

Like, periods can be horrible and painful or even just really annoying.

I think there's a big difference between annoying and shameful, right?

I mean, we've missed so much, not just about periods, but about

female and birthing bodies in general, because we have historically thought that they were disgusting and shameful.

There's so much potential in menstrual fluid, like so many treasures that could help so many people.

The real shame here would be if we let stigma get in the way of discovering those treasures.

This is the end of our series, The Bleeding Edge, but there is a lot more to explore here.

First of all, if you have endometriosis or you think you have endometriosis and you want to contribute to Christine and Peter's research, they would love new study participants.

So we will link to the Rose study in our transcript, but you can also just look up Rose study endometriosis to read more about the study.

And if you want to, enroll online.

If you want to hear more about endometriosis, we actually have an old episode about endo specifically that we will link to in the transcript.

And then if you want to read more about periods or about uteruses in general, I cannot recommend Leah Hazard's book, Womb, Enough.

She has more about Christine Metz's work in there, but also just all kinds of fascinating research on wombs and womb health.

We will also have a Q ⁇ A with Leah Hazard on our site.

This episode was produced.

and reported by me, Bird Finkerton.

It was edited by Jorge Just, Brian Resnick, and Meredith Hodnat.

Meredith also runs this show.

Noam Hasenfeld composed the music.

Christian Ayala did the mix and the sound design.

Melissa Hirsch did our fact-checking.

And Manning Nguen is the fact that female phal ropes are not only bigger than male ones, but also more colorful.

This podcast and all of Vox is free because of gifts from our readers and listeners.

You can go to vox.com slash give to give today,

or, or I guess, and/or,

you can support the show by leaving us a review.

Reviews make a very big difference for our show.

And then, if you have thoughts or feelings about periods or menstruation or endometriosis, or just ideas about other episodes that we should do, please email us with your thoughts or questions.

We are at unexplainable at vox.com, and I definitely read every email.

Unexplainable is part of the Vox Vox Media Podcast Network, and we will be back next week.

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