Dr. Taylor: Endometriosis is a very common disease. Unfortunately, it's still widely under-recognized. It's estimated that perhaps up to 10% of reproductive age women have endometriosis, yet many are never diagnosed or diagnosed late. The average time that it takes for someone to be diagnosed is about 10 years; that is from the time they have classic symptoms of endometriosis until the time they get a definitive diagnosis and treatment.
I think it's very important that we recognize the clinical features of endometriosis. It's absolutely crucial if we want to shorten the time tom diagnosis. Often patients see multiple physicians before they get an accurate diagnosis. They're often dismissed by their early caregivers who are not very familiar with the disease.
For me, the most important feature is the pelvic pain. To identify endometriosis, I look specifically at the cyclic nature of the pelvic pain, and the progressive nature of the pelvic pain. Endometriosis is by far the most common reason that women have pelvic pain and initially it tends to be cyclic. It often starts as dysmenorrhea (painful periods), however it can progress to the point where pain occurs at times outside of menses. In fact, it can progress to the point where it's painful all the time. However, it almost always starts as dysmennorhea, and progresses.
Pelvic pain that someone had from their first menses on, i.e., from menarche, is less likely to be endometriosis than the pain that progresses and becomes worse or spreads to other times of the menstrual cycle. Endometriosis is a progressive disease, and that's one of the key distinctions in making me think somebody has endometriosis.
Most women with cyclic pelvic pain that gets worse over time, cyclic progressive pelvic pain, will have endometriosis. Those are the key features I look for.
It is also very important to recognize that endometriosis can have effects outside of the reproductive tract, can cause systemic inflammation, and impact other organ systems. Bowel and bladder dysfunction are very common. If that is cyclic and coincides with the pelvic pain, it’s very likely to be secondary to endometriosis. It's important not to get distracted or mislead into making other diagnoses.
What are some of the common symptoms and how does that impact your diagnosis evaluation?
Dr. Taylor: The most common symptom we see is that cyclic pelvic pain I just discussed. Pain, often starting as dysmenorrhea, can go on to include pain outside of the time of menses and become more than just dysmenorrhea- pain in other areas. The other common symptom is infertility. Many women with endometriosis do not have severe pain or may not have pain at all, but first present when they have trouble conceiving.
Endometriosis may be the cause of infertility. Sometimes we recognize that it's endometriosis when we do a physical exam or an ultrasound and find an endometrioma. Cyclic pelvic pain is the classic symptom we look for, and infertility is another key symptom that we shouldn't forget.
Can you talk a little bit about empiric treatment, primarily what that means and how prevalent it is in your current practice?
Dr. Taylor: I think one of the problems we have today with the treatment of endometriosis is that it doesn't get recognized and doesn't get treated right away. When we talk about emperic treatment, it's usually ruling out other potential etiologies of pain. We must ensure no one has have an infection, a tumor or other etiologies that are the cause of the pain, and not simply presume that any cyclic progressive pelvic pain is endometriosis – however most of the time it will be due to endometriosis.
Usually with a good history, physical exam, and sometimes with addition of a transvaginal ultrasound, you can rule out other etiologies of pain, and have a very good idea that this pain is related to endometriosis. Based on clinical presentation, and without needing surgery, we can make a clinical diagnosis of endometriosis.
Clinical diagnosis allows patients to have this disease recognized earlier. It allows them to get into treatment sooner and reverses this trend that we've seen of delayed recognition. This delay is especially difficult in younger women in formative years in their life, when they're in school, when they're in an early stage of their career. If they're held back because of this debilitating pain, these are critical times and opportunities they really can't completely make up.
It's very important that we recognize endometriosis early. If we require a laparoscopy to make the diagnosis, the threshold becomes very high and we don't make the diagnosis. We miss a lot of women with endometriosis and don't treat them early.
There was time when our medical options were limited, and we wanted to be sure of our diagnosis. But these days, I think we can make a clinical diagnosis knowing that we have several treatment options that are relatively easy and safe for patients. Our first line therapy-- the first thing I use when I make the clinical diagnosis of endometriosis-- the first emperic treatment I would use is an oral contraceptive.
I prefer giving the oral contraceptive in a continuous fashion, rather than in a cyclic fashion. If someone has dysmenorrhea, why have menses at all? Retrograde menstruation is the etiology of most endometriosis. If we can eliminate menstruation, potentially it may be reducing endometriosis in the long run.
A lot of women with endometriosis will not respond to progestins—a phenomenon called progestin resistance—therefore, not everyone who has endometriosis will respond to an oral contraceptive. Probably about a third of patients either will not initially respond or will develop a resistance to a progestin and fail to respond in the long-term. Still others have side effects due to progestin therapy-- breast tenderness, mood changes, or a feeling of bloating are very common progestin related side effects.
We now have agents like oral GnRH antagonists that we can use as a second line treatment for those that either don't respond to progestins or those who have side effects from a progestin, including a progestin based oral contraceptive. Additionally, in those with severe pain you may want to use something a little more aggressive.
GnRH antagonists are easy to use oral medications, with an immediate onset of action and are easily reversed. We have come a long way from when we had to use an injectable GnRH agonist as the second line therapy. We have much simpler, easy, second line medications that we can turn to that makes empiric treatment a lot easier.
In the past, when we made a surgical diagnosis it was often because we were afraid of committing them to a long course of Depo GnRH agonist treatment; we didn't use a lot of add back therapy and they had tremendous side effects and the risk of bone loss. Patients and their physicians were reluctant to use GnRH agonists.
Things have gotten a lot easier with oral contraceptives, that can be followed by GnRH antagonists, which are easy to use, simple medications that are very patient-friendly. I think we can make that clinical diagnosis. We can move to an empiric treatment, either first or second line with an oral contraceptive or a GnRH antagonist and easily treat these women without significant side effects. It is important that we advocate for women with cyclic pain, and recognize it more readily, clinically diagnosed it, and begin that empiric treatment. That paradigm really has a huge impact on women's lives.
What recent advancements have been made in diagnosing and treating endometriosis?
Dr. Taylor: I think one of the biggest things that I see improving is recognition. Hopefully, we're narrowing that long delay by closing that time gap from initial symptoms to recognition. As we see public awareness grow, patients are recognizing and looking for answers, and thinking to themselves that they may have endometriosis.
Years ago, people were embarrassed to talk about menstruation, painful menstruation, pain with intercourse, pain with bowel movements. Thankfully, we're a more open society now and we can talk about these things. Women are starting to realize that they may have a problem where it was just dismissed before or perhaps, they were embarrassed to talk about it. I think we have seen a huge advancement. Physicians, as well, are recognizing endometriosis even more than before.
I think we're also much more accepting of this clinical diagnosis paradigm and empiric treatment. A lot of that, as we just said, comes from having better, easier to use drugs available that are much more patient-friendly. The GnRH antagonist elagolix is currently available for treatment of endometriosis in the United States. There are two more GnRH antagonists in the pipeline-- relugolix, which we expect to be approved shortly, and linzagolix which is undergoing phase three clinical trials now. Hopefully, we will have several of these second line drugs, drugs which we can even use first line for severe endometriosis. Their availability is another huge advance.
I also think it is essential, that we don't put someone through surgery to recognize endometriosis. We must be better at taking a good history, doing an exam, and ultrasound when needed. You don't need a surgery to diagnose endometriosis.
However, we do still sometimes need surgery to treat endometriosis. Often, endometriosis will cause adhesions or scarring. These long-term sequelae of endometriosis can still require surgery. The medications we have available today are very good at stopping active disease. But the damage done from long-term endometriosis if we don’t treat may still require surgery. I'm hoping that the earlier we start treating people, the less damage will be done, and the less therapeutic surgeries needed. I think these changes are coming and are all very promising.
It would also be great if we had a non-invasive definitive diagnostic test. There are several of those under development, but nothing available yet. I suspect that we'll see those become available very shortly.
The other thing that we still need in the field is a treatment we can use for those women trying to get pregnant. We use in vitro fertilization, which works very well in the endometriosis population. But a medical therapy that can suppress endometriosis and allow people to try to conceive without needing IVF is something I hope for in the future. A specific endometriosis therapy that is not hormonal, that targets the specific pathophysiology of endometriosis, is something that I'd like to see developed and many of us are currently working on.
I think there is a lot coming, but we've already moved the needle a long way. The GnRH antagonists have given us much more confidence in moving forward with clinical diagnosis and empiric treatment of this disease. It's a huge boon for women's health, allowing early recognition and preventing long-term complications of endometriosis.