Risk of cardiovascular disease and mortality among women with endometriosis: A systematic review and meta-analysis

Endometriosis has been associated with chronic inflammation and an atherogenic lipid profile. Studies report increased risks of stroke and coronary heart disease in women with endometriosis, highlighting the importance of considering cardiovascular prevention strategies for these women.

Iphigénie Cavadias, Lorraine Maitrot-Mantelet, Sandrine Perol, Mathilde Bourdon, Pietro Santulli, Louis Marcellin, Charles Chapron, Geneviève Plu-Bureau

First published: 27 November 2025

 https://doi.org/10.1111/aogs.70104

https://obgyn.onlinelibrary.wiley.com/toc/16000412/0/0

Transcript

SPEAKER_00 0:00

So if I told you that a disease affecting um nearly 200 million women, one that is almost exclusively treated as a reproductive issue, is actually a silent major driver of the world's number one killer. I mean, would you have any idea what I was talking about?

SPEAKER_01 0:16

Aaron Ross Powell Honestly, most people wouldn't. We have this tendency in modern medicine to heavily compartmentalize the human body. Right. You know, you go to a cardiologist for your heart, a gastroenterologist for your stomach, a gynecologist for your reproductive system.

SPEAKER_00 0:30

Aaron Powell Yeah, you stay in your lane, basically. Trevor Burrus, Jr.

SPEAKER_01 0:32

Exactly. The body gets divided into these zones, and we just assume what happens in one zone stays in that zone.

SPEAKER_00 0:37

Aaron Powell But I mean the walls between those medical zones are really starting to come down. So today we are taking a custom-tailored deep dive into a profoundly misunderstood space in women's health.

SPEAKER_01 0:48

Yeah, it's a really important topic.

SPEAKER_00 0:50

It is. We're looking at the grounding material from a 2025 systematic review and meta-analysis. This was published in the journal Acta Obstite Gynecole Scan, and it was led by author Iphigenie Cavadias and her research team.

SPEAKER_01 1:03

And the mission of this research, I have to say, is entirely paradigm shifting.

SPEAKER_00 1:07

Oh, absolutely.

SPEAKER_01 1:08

It takes endometriosis, which, you know, for decades has just been boxed in as a pelvic pain and infertility disorder, and it links it directly to cardiovascular disease.

SPEAKER_00 1:18

Aaron Powell Okay, let's unpack this.

SPEAKER_01 1:19

Yeah.

SPEAKER_00 1:19

Because if we want to understand how a condition in the pelvis is quietly attacking the heart, we really have to look at the sheer massive scale of what we're actually dealing with here. Trevor Burrus, Jr.

SPEAKER_01 1:28

Right. So to set the stage for you, endometriosis affects roughly 10% of women of reproductive age.

SPEAKER_00 1:34

Aaron Powell, which is a huge number.

SPEAKER_01 1:36

It's massive. The World Health Organization puts that at around 190 million people globally.

SPEAKER_00 1:40

Wow.

SPEAKER_01 1:41

Yeah. And it happens when tissue that's similar to the lining of the uterus, uh, so the endometrium grows outside the uterus.

SPEAKER_00 1:48

So it's growing where it absolutely shouldn't be.

SPEAKER_01 1:50

Exactly. It attaches to the ovaries, the fallopian tubes, uh, the tissue lining the pelvis.

SPEAKER_00 1:56

Yeah.

SPEAKER_01 1:56

And it bleeds, it creates lesions, it causes severe scarring, and it triggers just immense chronic pain.

SPEAKER_00 2:03

And historically, the medical focus has basically stopped right there. Right? Like the pain, the scarring, the fertility challenges.

SPEAKER_01 2:10

Trevor Burrus, Jr.: Yeah. That's been the whole picture for a long time.

SPEAKER_00 2:12

Aaron Powell But Cavadius and her team are reframing this entirely. I mean, they are telling the medical community to stop looking at this as just a localized anatomical problem and start treating it as a chronic, estrogen-dependent inflammatory disease.

SPEAKER_01 2:28

Aaron Powell And that reframing is critical when we uh when we zoom out to the global stage of cardiovascular disease, which we'll just call C V D today. So in 2019 alone, CVD claimed 17.9 million lives.

SPEAKER_00 2:42

That's that's staggering.

SPEAKER_01 2:43

Aaron Powell It is. That's 32% of all deaths worldwide. And the vast majority of that stems from strokes and coronary heart disease. Right. Now we've made huge strides in treating heart disease over the last few decades. Like in places like the European Union, avoidable mortality from cardiovascular diseases has dropped significantly.

SPEAKER_00 2:59

Aaron Powell But there's a massive catch in that data.

SPEAKER_01 3:01

Aaron Powell There really is.

SPEAKER_00 3:02

Men have experienced a much larger decrease in preventable deaths than women have. I mean, the gap is just glaring. Women's heart risks are consistently being underestimated and under-treated.

SPEAKER_01 3:13

Yeah, and that's largely because the baseline for heart health research well, it was built around middle-aged men for decades. Trevor Burrus, Jr.

SPEAKER_00 3:20

Right, the classic, you know, chest clutching symptom that we always see in movies.

SPEAKER_01 3:24

Exactly. We have our traditional risk factors, so high blood pressure, type 2 diabetes, smoking, high cholesterol.

SPEAKER_00 3:30

The usual suspects.

SPEAKER_01 3:31

The usual suspects. But researchers are finally pinpointing risk factors that are entirely unique to women.

SPEAKER_00 3:38

Like what?

SPEAKER_01 3:38

Well, conditions like early menopause, migraines, polycystic ovary syndrome, and adverse pregnancy outcomes, things like preclampsia. Got it. And what this 2025 review demonstrates is that endometriosis must be added to that list as a major independent cardiovascular risk factor.

SPEAKER_00 3:56

Aaron Powell You know, it's like we've been treating endometriosis as a localized fire in the kitchen, but entirely ignoring the fact that the chronic smoke is seeping into the walls and damaging the entire foundation of the house.

SPEAKER_01 4:07

That is a perfect way to look at it.

SPEAKER_00 4:09

Right. Like we keep trying to put out the flames in the pelvis, but the house is quietly weakening. So we need to look at what the data actually says about this systemic smoke damage.

SPEAKER_01 4:18

And the rigor of this 2025 review gives us a very clear picture of that damage. I mean, the researchers didn't just look at a few small trials here.

SPEAKER_00 4:27

No, they went big.

SPEAKER_01 4:28

Very big. They started with 1,417 references and painstakingly filtered them down to 12 high-quality cohort studies.

SPEAKER_00 4:38

Wow. That is a lot of filtering.

SPEAKER_01 4:39

Yeah. And these studies span the US, the UK, Taiwan, Denmark, Canada, and Finland.

SPEAKER_00 4:45

Aaron Powell I noticed they pulled from some really massive legendary data sets too, like the Nurses Health Study 2 in the U.S. and the National Health Insurance Database in Taiwan.

SPEAKER_01 4:54

Oh, yeah. Those are gold standards.

SPEAKER_00 4:56

Right. So we are looking at millions of person years of observation. And the numbers they found are not, you know, just minor bumps in probability.

SPEAKER_01 5:04

Not at all. The pooled relative risks from the meta-analysis are genuinely striking. So for stroke, women with endometriosis showed an 18% higher risk.

SPEAKER_00 5:14

18%.

SPEAKER_01 5:16

Yeah. And then when you look at coronary heart disease, it's a 36% higher risk. Oh wow. And for a composite of cardiovascular diseases, which is a combination of these severe events, the data shows a 16% increased risk overall.

SPEAKER_00 5:31

I mean, let's just pause on that 36% spike in coronary heart disease for a second. If your baseline risk for a heart attack is already climbing as you age naturally, adding a 36% multiplier on top of that simply because of a gynecological condition is a massive red flag. It's a huge deal. And here's where it gets really interesting. I notice in the research that this risk isn't just a blanket statement, it actually changes depending on where the endometriosis is located.

SPEAKER_01 5:58

Yes, the review highlights a fascinating genetic study to prove exactly this. They looked at specific endometriosis subtypes.

SPEAKER_00 6:05

Like where the lesions actually grow.

SPEAKER_01 6:07

Exactly. Like whether the lesions were on the ovary or the pelvic peritoneum, or if the patient also experienced concurrent infertility.

SPEAKER_00 6:14

And what did they find?

SPEAKER_01 6:15

Those specific presentations were linked to even higher risks of ischemic stroke.

SPEAKER_00 6:20

And the way they proved that is really clever. The researchers use something called Mendelian randomization.

SPEAKER_01 6:26

Right, which sounds very intimidating.

SPEAKER_00 6:28

It sounds incredibly dense, but let's break that down for you because it's actually an elegant concept. Basically, instead of just observing people and hoping you didn't miss something, you look at their genetics.

SPEAKER_01 6:40

Yeah, because genes are set from the start.

SPEAKER_00 6:42

Right. Genes are randomly assigned at birth, like a natural coin flip. So if you have the genetic markers that predispose you to a specific type of endometriosis, and you also have a higher rate of stroke, researchers know it's a direct biological link, not just a coincidence about your lifestyle choices.

SPEAKER_01 7:01

What's fascinating here is that that genetic link helps eliminate a lot of the noise in observational data.

SPEAKER_00 7:06

Aaron Powell Yeah, the confounding variables.

SPEAKER_01 7:08

Exactly. But even in the standard cohort studies they reviewed, the researchers deliberately adjusted for those traditional lifestyle factors anyway.

SPEAKER_00 7:15

Oh really?

SPEAKER_01 7:16

Yeah. They stripped away the influence of age, body mass index, smoking history, and diet. And the data still showed the exact same spikes in heart disease and stroke.

SPEAKER_00 7:26

Aaron Powell So it's not the smoking or the weight doing it?

SPEAKER_01 7:28

No. Endometriosis itself, the actual disease process, is driving the cardiovascular risk.

SPEAKER_00 7:34

Aaron Powell Okay, so if it's not the traditional factors like smoking or weight, I mean the only thing connecting the pelvis to the heart is the bloodstream. So is the body just pumping out continuous stress signals or inflammatory markers into the blood?

SPEAKER_01 7:47

Yes. That is the core biological domino effect we are talking about. The underlying mechanism is systemic chronic inflammation.

SPEAKER_00 7:55

Aaron Powell Which we hear a lot about these days.

SPEAKER_01 7:57

We do, but here's how it works with this condition. When a patient has endometriosis, their immune system is in a constant exhausting battle with this misplaced tissue.

SPEAKER_00 8:07

Right, because it doesn't belong there.

SPEAKER_01 8:09

Exactly. The body keeps trying to heal or clear away lesions that shouldn't be there, which elevates inflammatory factors and markers of oxidative stress in the blood continuously.

SPEAKER_00 8:19

So it's like an engine running constantly in the red zone.

SPEAKER_01 8:22

Aaron Powell That's a great analogy. And over time, that chronic inflammation promotes what cardiologists call endothelial dysfunction.

SPEAKER_00 8:29

Endothelial dysfunction. Okay, what is the endothelium exactly?

SPEAKER_01 8:32

The endothelium is the delicate, ultra-thin membrane that lines the inside of your heart and literally all your blood vessels.

SPEAKER_00 8:40

Aaron Powell You can think of the endothelium almost like the nonstick Teflon coating on a frying pan.

SPEAKER_01 8:46

Oh, I like that.

SPEAKER_00 8:47

Right. It's supposed to be perfectly smooth, so blood cells slide right past without sticking or clotting, and it's supposed to be flexible so the vessels can expand when your heart pumps harder.

SPEAKER_01 8:56

Aaron Powell Right. And endothelial dysfunction basically means that nonstick coating is deteriorating.

SPEAKER_00 9:01

Yikes.

SPEAKER_01 9:02

Yeah, the vessels lose their ability to relax and contract properly. This leads directly to arterial stiffness.

SPEAKER_00 9:09

Even without high blood pressure.

SPEAKER_01 9:10

Yes, exactly. What the studies reveal is that this stiffening happens in endometriosis patients even if their blood pressure is completely normal.

SPEAKER_00 9:18

Aaron Powell That is wild.

SPEAKER_01 9:20

One of the studies in the review actually measured this physical stiffness by looking at something called advanced glycation end products.

SPEAKER_00 9:26

Aaron Powell Which sounds like a term straight out of a chemistry textbook. Advanced glycation end products. Help me puzzle this out. Glycation usually refers to sugar bonding to things, right?

SPEAKER_01 9:36

Aaron Ross Powell It does, yes. When sugars bind to proteins or fats in the bloodstream without an enzyme to control the process, they form these advanced glycation end products, or AGEs for short.

SPEAKER_00 9:48

Okay, so how should we visualize that?

SPEAKER_01 9:50

You can literally think of it like caramelizing sugar in a pan.

SPEAKER_00 9:53

Oh wow.

SPEAKER_01 9:54

Yeah. It turns proteins that are supposed to be soft and flexible into something stiff and brittle. And the researchers found a higher accumulation of these brittle proteins in the skin and vessels of women with endometriosis compared to healthy controls.

SPEAKER_00 10:08

So it's not just a theory.

SPEAKER_01 10:09

No, it is a measurable physical marker of premature vascular aging.

SPEAKER_00 10:14

Okay, wait, I have to push back here on the logic of how we treat this.

SPEAKER_01 10:17

Go for it.

SPEAKER_00 10:18

Because if inflammation from the pelvic lesions is the root cause of this vessel caramelization and stiffening, shouldn't treating the endometriosis lower the heart risk? Like you surgically remove the tissue, you put out the fire, the house stops smoking, you save the heart.

SPEAKER_01 10:33

The biology definitely suggests that should work. And one study actually backed that up.

SPEAKER_00 10:37

Oh, really?

SPEAKER_01 10:37

Yeah. They measured an ethelial function using flow mediated dilation.

SPEAKER_00 10:40

Aaron Powell Flow mediated dilation. You just mean measuring how well a blood vessel can stretch and open up when blood rushes through it.

SPEAKER_01 10:47

Aaron Powell Yes, exactly. They briefly restrict blood flow in the arm, then release it and use an ultrasound to see how well the artery dilates to handle that sudden rush of blood. Okay. And in women who underwent surgical treatment to remove their endometriosis lesions, that arterial stretching ability actually improved. The dysfunction regressed.

SPEAKER_00 11:07

Okay. So surgery works to protect the heart, problem solved.

SPEAKER_01 11:10

Uh well if only it were that simple.

SPEAKER_00 11:13

Oh no.

SPEAKER_01 11:14

Yeah. This introduces arguably the most frustrating paradox in this entire deep dive.

SPEAKER_00 11:18

Lay on honey.

SPEAKER_01 11:19

While removing the lesions might temporarily reduce inflammation, many of the standard long-term treatments for endometriosis actively increase cardiovascular risk.

SPEAKER_00 11:28

Wait, they increase it?

SPEAKER_01 11:29

Yeah. Let's look at surgical menopause. For severe cases, surgeons will perform a bilateral cell pingouphorectomy.

SPEAKER_00 11:36

Which means removing both ovaries.

SPEAKER_01 11:38

Right, often alongside a hysterectomy. And the goal there is to stop the body from producing the estrogen that essentially feeds the endometriosis.

SPEAKER_00 11:45

But estrogen is doing a lot more than just fueling the pelvic lesions, right?

SPEAKER_01 11:49

So much more. Estrogen is heavily cardioprotective.

SPEAKER_00 11:53

Okay.

SPEAKER_01 11:54

It helps the body produce nitric oxide, which is the chemical that keeps those blood vessels relaxed and flexible. It also helps regulate cholesterol levels.

SPEAKER_00 12:03

So when you take the ovaries out.

SPEAKER_01 12:05

When you surgically strip a woman's body of estrogen, especially when she is in her thirties or forties, you drastically accelerate her risk of cardiovascular disease compared to someone who goes through natural menopause later in life.

SPEAKER_00 12:18

Man. So the surgery cures the agonizing pelvic pain, but it strips the heart of its primary chemical defense system.

SPEAKER_01 12:26

Exactly. And we see a very similar problem with the primary medical treatments, too. Doctors frequently prescribe gonadotropin-releasing hormone analogues or gene RHA.

SPEAKER_00 12:36

Right, I heard of those.

SPEAKER_01 12:37

These drugs are designed to suppress ovarian function and stop the menstrual cycle entirely to starve the endometriosis of estrogen.

SPEAKER_00 12:44

They induce what the review calls hypothalamic amonrhea. Let's break that phrase down for you. The hypothalamus is the control center in the brain, and emanorrhea means the absence of a period. Right. So the drug essentially tells the brain to stop sending the signals that tell the ovaries to work at all.

SPEAKER_01 13:02

Aaron Ross Powell You are artificially inducing a menopausal state. Wow. And yes, the pain stops, but once again, you are creating a low estrogen environment. Sustained low estrogen means the blood vessels lose that vital flexibility and the long-term cardiovascular risk just begins to climb.

SPEAKER_00 13:20

Aaron Powell Okay, so because the disease itself is attacking the blood vessels with inflammation, and the treatments to stop the disease are attacking the blood vessels by removing estrogen, you would naturally assume this double-edged sword drastically spikes the overall death rate.

SPEAKER_01 13:34

You would think so, yeah.

SPEAKER_00 13:35

If the disease causes strokes and the treatments also cause heart disease, the mortality data should just be a straight line pointing up.

SPEAKER_01 13:42

But actually the mortality data is incredibly messy.

SPEAKER_00 13:45

Yeah. When the researchers analyzed the risk of all-cause mortality, which means death from any cause, and specific cardiovascular mortality, the data showed high heterogeneity.

SPEAKER_01 13:57

Meaning it was all over the map.

SPEAKER_00 13:59

The results were wildly all over the place.

SPEAKER_01 14:01

Think about how confusing this is. The review highlights a 2019 study out of Finland led by Savalanin that looked at 2.5 million person years of observation.

SPEAKER_00 14:12

That's a massive study.

SPEAKER_01 14:14

Huge. And they actually found that women with endometriosis had a decreased risk of mortality. I mean, they were surviving longer than the healthy control group.

SPEAKER_00 14:21

Which directly contradicts the 36% spike in coronary heart disease we literally just talked about.

SPEAKER_01 14:26

Right. So how does that make any sense? Well, the working theory behind this finished study is a phenomenon we actually see often in chronic illness.

SPEAKER_00 14:33

Okay.

SPEAKER_01 14:33

Women dealing with laparoscopically confirmed endometriosis are constantly interacting with the healthcare system.

SPEAKER_00 14:40

Ah, they're always at the doctor.

SPEAKER_01 14:42

Exactly. They're seeing specialists, getting blood work, having their blood pressure checked regularly. Because they are in the system managing their pain, doctors inadvertently catch other life-threatening issues like high cholesterol or early stage diabetes much sooner than they would in a woman who rarely visits a doctor.

SPEAKER_00 15:02

It's an accidental safety net.

SPEAKER_01 15:03

Exactly.

SPEAKER_00 15:04

But contrast that with a massive 2024 U.S. study by Wang, utilizing the Nurses Health Study 2. They followed over 110,000 nurses for 27 years.

SPEAKER_01 15:16

Another incredible data set.

SPEAKER_00 15:18

And they found the exact opposite of the Finnish study. They found a statistically significant increased risk of premature mortality for women with endometriosis.

SPEAKER_01 15:27

This raises an important question, though. The differences between these two studies reveal the inherent challenges of observational data.

SPEAKER_00 15:34

How so?

SPEAKER_01 15:34

You really have to look closely at how the disease was diagnosed and who is actually being included in the data set. In some older studies, a diagnosis of endometriosis was based purely on clinical suspicion.

SPEAKER_00 15:44

Aaron Ross Powell Meaning they didn't actually look inside the body.

SPEAKER_01 15:46

Right. A patient comes in with severe menstrual cramps and pelvic pain, and the doctor writes down suspected endometriosis, but they never definitively prove it.

SPEAKER_00 15:56

Whereas in the U.S. Nurses' Health Study, the diagnosis was laparoscopically confirmed. They went in surgically and literally saw the physical lesions. The nurses definitively had the disease and their premature mortality risk went up.

SPEAKER_01 16:09

Exactly. And furthermore, the diagnostic landscape is shifting right under our feet. Because radiological imaging like specialized ultrasounds and MRIs has improved so dramatically in recent years, fewer women are undergoing diagnostic surgeries just to see if they have the disease.

SPEAKER_00 16:26

Because doctors can often just see deep infiltrating endometriosis on a scan now.

SPEAKER_01 16:30

Right.

SPEAKER_00 16:31

But that introduces a new problem for researchers trying to track mortality, doesn't it? Yeah. If a woman has superficial endometriosis like tiny lesions that just don't show up on an MRI and she doesn't get the diagnostic surgery, she might be placed in the healthy control group of a study.

SPEAKER_01 16:45

Yes. That misclassification bias completely skews the data.

SPEAKER_00 16:49

Oh, I see.

SPEAKER_01 16:50

If the quote unquote healthy group actually includes thousands of women with undiagnosed endometriosis who go on to have heart attacks, the statistical difference between the groups shrinks.

SPEAKER_00 16:59

Aaron Powell Which masks the true danger of the disease.

SPEAKER_01 17:02

Aaron Ross Powell Exactly. It makes the disease look less deadly than it actually is.

SPEAKER_00 17:06

Aaron Ross Powell So the long-term mortality data is essentially just a giant knot of conflicting variables, changing technologies, and totally different healthcare systems.

SPEAKER_01 17:14

Pretty much.

SPEAKER_00 17:14

But the messy long-term data doesn't negate the immediate proven biological damage we talked about earlier. The 36% spike in coronary heart disease, the 18% spike in stroke risk, the early stiffening of the arteries. That is undeniable.

SPEAKER_01 17:28

It is undeniable. The conclusion from Comadius and her team is completely unequivocal on this. Endometriosis is an emerging cardiovascular risk factor specific to women, and the medical community can no longer afford to view it in isolation.

SPEAKER_00 17:42

So what does this all mean for your health?

SPEAKER_01 17:43

Yeah.

SPEAKER_00 17:44

I mean, it means endometriosis is not just a painful period. It is not just an infertility hurdle. It is a blaring alarm system for your long-term cardiovascular health.

SPEAKER_01 17:54

And the clinical takeaway here is a demand for a massive shift in patient care.

SPEAKER_00 17:58

We really need it.

SPEAKER_01 18:00

We do. Modern endometriosis management must move beyond simply treating pain and fertility in a gynecologist's office. It requires an interdisciplinary approach for the patient's entire endometriosis life.

SPEAKER_00 18:11

Not just checking in once a year. No.

SPEAKER_01 18:14

Women with this condition need immediate and more importantly, repeating cardiovascular risk assessments starting at a much younger age.

SPEAKER_00 18:21

We're talking about aggressively deploying primary cardiovascular prevention strategies, right? Checking blood pressure regularly, screening for lipid and diabetes, monitoring for migraines with aura, and taking a very deep look at the family history of early cardiovascular disease.

SPEAKER_01 18:36

Exactly. And if we connect this to the bigger picture, this research fundamentally empowers patients.

SPEAKER_00 18:42

How so?

SPEAKER_01 18:42

Well, if you or someone you know is managing endometriosis, this data allows you to advocate for your whole body health. It gives you the peer-reviewed evidence to walk into a primary care doctor's office or a cardiologist's clinic and say, hey, my gynecological history puts my vascular system at risk, and we need to monitor my heart proactively.

SPEAKER_00 19:02

It breaks down those silos between medical specialties that we talked about at the very beginning.

SPEAKER_01 19:06

It absolutely does.

SPEAKER_00 19:07

It's about treating the whole house, not just the room where the fire started. We assumed the medical diagnosis was confined entirely to the pelvis, but the smoke damage is systemic.

SPEAKER_01 19:17

Perfectly said.

SPEAKER_00 19:18

I want to thank you for joining us on this deep dive. And I want to leave you with a lingering thought to mull over today. If a condition historically dismissed by so much of the medical world as quote unquote just a reproductive issue is secretly rewriting the cardiovascular health of nearly 200 million women, what other highly localized, poorly understood conditions might be acting as silent drivers for systemic life-threatening diseases right under our noses?