Endometriosis Unraveled: Defining, Diagnosing & Treating

[Dr. Mark Hoffman]
To Amy's point, what's the latest understanding for the pathophysiology of endometriosis? Because the whole, whatever the theory is, like you mentioned we learned in third year of med school, you know when you have a patient that's got Mayer-Rokitansky so doesn't have a uterus or vagina and has endo, well that's not retrograde menstruation, but those patients can have endometriosis. None of those things individually seem to fit to explain all of it. Can you educate us on what is the latest or best theory about where endometriosis comes from, how it proliferates, how it causes pain?

[Dr. Isabel Green]
Yes, I wish I had a really good answer for that. Thanks for that [laughs] difficult question, but it's funny because we keep saying it is that it's probably different in different people. When we look at the studies of retrograde menstruation, that doesn't make sense for people that don't have retrograde menstruation and doesn't make sense for the 80% of people that probably have that every month but then don't end up with endometriosis.

There's some great work and if we can keep developing these pathophysiologic mechanisms, then that will hopefully lead to better diagnostics, better therapeutics, but some interesting work in genetic susceptibility, which is probably a small percent differences and dysregulation that happens, so with inflammatory cytokines autoimmune dysregulation, and these are all really broad general ideas. I think you could bring a basic scientist on to talk about which cytokine and which different specific biomarker. It's good and exciting to see that that is an area of research right now, so looking at changes in the immune system, looking at changes in angiogenesis, the development of-- it's almost like it's cells that are converting and acting like malignancy without a malignancy.

There's so much, I think, there to learn and I feel like when I am reading the manuscripts and the papers, I am barely touching the surface, so it's almost like I depend on our basic science colleagues and the people that are doing the research to look at which biomarkers could be useful. I think that's incredible. I can't answer the specifics of it, but just it's complex.

[Dr. Mark Hoffman]
That's the most, I think, challenging part for those of us that do this is you never want to tell a patient, "I don't know," but I do it all the time. I just say, "We don't know where it comes from chronic pelvic inflammation," so are the changes that are coming to the nervous system or the soft tissue and the fibrosis, is that coming from the endometriosis? What's causing what? It's hard to understand any of it when we don't know the pathophysiology, we don't know where it begins.

I think that's something that, it'll be an exciting day for me. Hopefully, it won't be too long before we start to understand better where this is coming from. Knowing that this is a mysterious disease, one that presents oftentimes early, but is diagnosed late, why do you think that delay comes? Is it just simply we manage patients medically and they don't actually have the diagnosis for surgery till later? Do you think women aren't being heard? Do you think it's all the things? Why is this such a challenging disease to diagnose?

[Dr. Isabel Green]
Yes, I think you're right in that it's probably a combination of factors and that a lot of our research depended on actual official surgical diagnosis of endo. That's even already thinking about that. Our understanding of this disease are only people that ultimately went to have surgery. That's already this interesting lens in which to understand an illness. The big challenges with endometriosis are the fact that we talked about this earlier, there can be a variety of symptoms.

Someone might have very painful periods, not just a bad period, very painful period that leads to missing work, missing school, things like that. Another patient might have pain that exists outside of the cycle, so non-cyclical pain, so daily pain. There can be different manifestations and different levels of the number of days in any month that someone is symptomatic. Probably the irony is that we can be dismissive even when it gets severe to daily, and we can be dismissive and normalize the symptoms when they're cyclic and just monthly.

There's probably a lot of patients that initially get treated for just dysmenorrhea and are treated medically for dysmenorrhea with NSAIDs or a birth control pill and don't really ever get to that diagnosis of endometriosis as the source of that symptom. Dysmenorrhea is a symptom, not necessarily a disease. We know that people can see six to seven visits with their primary care provider before getting a referral to a gynecologist, and it can take up to 12 years, especially for our young patients to get these diagnoses.

I think part of it is that we're very used to treating the symptoms of endometriosis as almost a normal part of the menstrual cycle, and we're just going to treat the dysmenorrhea but not necessarily reach that diagnosis of endo, and then hone in on that as a disease. In a way, it's good that diagnostic laparoscopy isn't necessary anymore to treat endo, you can do empiric treatment, you can have a working diagnosis of endometriosis, but I think a lot of people are stuck in this medical management treatment of dysmenorrhea before getting to endo. They might be on their fourth medical therapy for treatment of dysmenorrhea but not have a diagnosis of endometriosis.

[Dr. Mark Hoffman]
What's your algorithm? If a patient comes to you first time being seen by a gynecologist, has painful periods and I write in my notes a lot presumed endometriosis or suspected endometriosis because, like you said, I feel like we can treat these patients as if they had it without having to have surgery, doesn't mean we're not-- those of us that do it I feel like everybody's got endometriosis, it's just a matter of time until we find it. Again, what do you mean when you say, I guess, should we be finding it sooner?

[Dr. Isabel Green]
Yes. This is a great question. I think even to throw back at you in the sense of if a patient undergoes first-line treatment for dysmenorrhea, that would be medications, so a form of suppression, birth control pill is usually the first line. Then, when we think about pain is a medical failure, does that make that clinician think, well then this couldn't possibly be endo because I have you on a birth control pill and it's not getting better, or does that clinician say you could have endometriosis and you failed the first line of treatment, which is medical therapy.

We're very systems driven which is funny that we talked about that before, Amy, but we're very systems driven in healthcare. The gastroenterologist rules out inflammatory bowel disease and cancer for patient with certain bowel complaints and the gynecologist rules out this. If a patient is having a failure of a medical therapy, one thought is that it can't be endo. You're not having your period and you still have pain but failed medical therapy is also a symptom of endometriosis. Does that make sense? It's like you shouldn't necessarily get to your fourth medication for medical suppression without more than a working diagnosis of dysmenorrhea and endometriosis.

[Dr. Mark Hoffman]
Right. I think for me if a patient's tried something and failed, the medications failed them in that sense, or if it's worth, neither of them tell me whether they have endometriosis or not, if they're taking continuous birth control pills and their symptoms are well controlled, they could have endometriosis, they could not. They could take birth control pills and continue to have pain and they could have endometriosis or they could not have endometriosis. It doesn't help me make a diagnosis at all. [chuckles] That's part of the challenge for me. That's the frustrating thing about this disease, but that's where diagnosis can be helpful in that it allows us to, at least, tell the patient something but outside of the excision part, how often does it change our management to know?