Ja Hyun Shin, MD
Questions your doctor forgot to ask and early misdiagnosis
Patient Awareness Day
The Lifecycle of Endometriosis: From Diagnosis to Coping with Disease
Sunday April 17, 2016
Lenox Hill Hospital, Einhorn Auditorium
Good morning everyone, I would like to thank Dr. Seckin and the Endometriosis Foundation for inviting me to speak today. Here at the conference we can all share our knowledge and what we know and continue to learn from each other and become experts by the end of these three days. I have nothing to disclose.
Dr. Seckin touched upon some of these things but I wanted to start my talk with the fundamentals and epidemiology of endometriosis and a lot of this material is going to be reinforced throughout the next few days. What is the definition of endometriosis? It is the presence of endometrial glands and stroma outside the uterus that can lead to chronic pain and infertility. Where do you find endometriosis? You can find it in the pelvic organs such as the ovaries, tubes and the peritoneum. This is the membranous lining of your abdominal cavity, the surface of the uterus, vagina and cervix. You can find it in nearby structures such as the bladder and bowel and really anything in between. You can find it outside the pelvis in the abdominal wall, surgical sites and even more remote organs such as the brain, liver and lung.
When do you get endometriosis? It can really happen any time but typically after menarche, which is when a woman first starts her periods and before menopause. Why does endometriosis occur? This is really a multifactorial disease, there are multiple theories including retrograde menstruation where there is backflow of your period into your abdominal cavity spread by blood by the lymph system. The differentiation of pluripotent stem cells and a concept called metaplasia, which is basically the idea of one cell changing for another cell.
There can be immunological factors, genetics, anatomic and iatrogenic and this is when endometrial tissue is transplanted from the uterus to another site of the body, for example, during a Cesarean section that can lead to endometriosis on the abdominal wall. It can be associated with a strong family history, early menarche, nulliparity that is the inability to complete a pregnancy, short and heavy menstrual cycles, BMI, lifestyle and environmental factors, lots of issues.
Who is getting endometriosis? It is pretty prevalent, 10 to 15 percent of reproductive age women, 30 to 50 percent among women with pelvic pain and/or infertility and almost up to 90 percent of women with chronic pelvic pain.
The rest of my talk is going to focus on early diagnosis that begins with adolescence and there is a wide range in terms of prevalence, from 25 to 75 percent depending on what you read in adolescents with pelvic pain that ultimately do have endometriosis.
How is endometriosis definitively diagnosed? Histologically, and what this means is that you take the patient to the operating room, you perform a diagnostic laparoscopy, take biopsies or complete a full excision, send it off to the lab and get a pathology report that reads as glands and stroma suggestive of endometriosis. Unfortunately, even though endometriosis is quite a prevalent disease it is being diagnosed much later than it should. Many women suffer for really an unacceptably long time before they can reach a proper diagnosis and be treated. Fifty percent of adult women report their symptoms began in adolescence. There can be an average delay in diagnosis of approximately seven years and an average of two to three providers before diagnosis is actually made.
One of the obstacles to diagnosing this disease is that if as an adolescent or young woman you presented to the emergency room with severe pain unfortunately imaging does not really work for you. Unlike fibroids it is not something that you can detect on ultrasound or MRI. And there is no blood test say like for an infection that is going to pick up endometriosis. So what they see is someone complaining of really, really painful periods and often times, if not in the ER, they can be told by their pediatrician or even the gynecologist or primary care doctor that “Your painful periods are normal”.
This is definitely a misconception and painful periods requiring medical care or certainly negatively affects your quality of life compared to others in your same age group is not normal and it should be evaluated.
What are the signs and symptoms to look for? You can have severe painful periods that can be cyclic and correlates with your menses or can be independent of your menses. You can have painful intercourse, abnormal uterine bleeding and infertility. An important one is you can also get symptoms from co-morbid pain syndromes such as interstitial cystitis, otherwise painful bladder syndrome, irritable bowel syndrome or because of implants that are located on different organs other than just your pelvic organs.
What are some of the urinary symptoms you may feel? Patients with endometriosis may feel pain with full bladder, increased urinary frequency and urgency and nocturia, which is the need to get up in the middle of the night how many times because of the urge to have to void. Also you can have GI symptoms such as diarrhea, constipation and bloating.
As stated earlier there is a wide range reported for the prevalence of endometriosis in adolescents and that is because the true prevalence in this group is unclear because it can only be diagnosed laparoscopically.
This is a study that came out of Belgium. It was a literature review of published articles from 1980 to 2011 and included a total of 15 studies. The primary outcome was what was the prevalence of endometriosis in adolescent girls undergoing laparoscopy, a diagnostic laparoscopy, because they were having pelvic pain that was refractory to treatment or they may have just had painful periods or they may have had pain that responded somewhat to treatment. In these categories how many of these girls actually had endometriosis? This was their way of assessing that based on the wide range that is reported out there. Not surprisingly they also reported a wide range of 25 percent up to 100 percent in some studies. The overall of all these studies of prevalence of visually confirmed endometriosis is 62 percent. If you were to break it down 75 percent of women, adolescents with chronic pelvic pain that is resistant to treatment with first line therapy. They come to you with pelvic pain and severe periods, painful periods you treated them with NSAIDs it did not work; you add OCPs on top of that it did not work and then you take them to the operating room. Of these women with that kind of history almost three quarters, if not more, will actually have endometriosis. If they just have painful periods as their only symptoms, again, the “normal painful periods” up to 70 percent of them will have endometriosis.
This is another study that came out of the University of Michigan. It was a retrospective review of 138 adolescents and young women again who already had their surgery and had visual or biopsy confirmed diagnosis of endometriosis. What these authors looked at were the prevalence of other pain syndromes and mood conditions, as well as asthma. The reason they looked at asthma was that there have been studies that have demonstrated some kind of correlation between autoimmune atopic, which means an allergy related condition to endometriosis, and asthma was one of them.
What they found was that of these girls who already had a diagnosis of endometriosis based on symptomatology and their strict criteria for some of these things, not all of them, some of these things a quarter of them also had concurrent IBS, irritable bowel syndrome and suffered from chronic headaches, had ICPBS and some less common symptoms. It is not surprising that almost 50 percent of them also suffer from depression and/or anxiety. Almost a quarter also had asthma. Basically what this study shows is that pain should not be ignored, painful periods should not be ignored and that there are other pain syndromes that can co-exist with endometriosis. Sometimes treating just the endometriosis might not be enough and you might need more comprehensive care. I do want to point out what I think personally is a limitation of these studies in that in both these studies they state that the diagnosis was confirmed by laparoscopy. But in that lump they state both visual and biopsy. The truth is really diagnosis is by biopsy. It has to be confirmed. You can suspect something is endometriosis and the actual positive predictive value or the chances that what you think is endometriosis is endometriosis is not perfect. It is far from that. It is closer to like 60 percent of the time you are right. You want to do a complete excision, biopsy everything you see to make sure you get the correct diagnosis.
Why is early diagnosis important? Well certainly pain can affect a young woman’s academic and social development. It is well established that increased absenteeism from school and work is very closely tied to severe dysmenorrhea. The early intervention can possibly decrease disease progression and preserve fertility and I say possibly, even though it makes sense, that the earlier you catch it the more likely you are to progress the disease. But the truth is we really do not fully understand yet the natural course of the disease. Some people may have a stage of the disease and that might be the stage that they always have. Or, others may progress from a milder stage to a severe stage. Regardless, an important point is the pain does not correlate with the stage of the disease.
These are my recommendations to early diagnosis and management. There is not a protocol but I guess this is kind of my algorithm. I tell my residents and fellows that over 90 percent of your diagnosis is going to be in your history taking. A careful history based on their symptoms you can definitely put endometriosis at the top of your differential diagnosis. A pelvic exam in only select patients; you do not need to examine every adolescent that comes into your office, especially if they have not yet engaged in vaginal intercourse. Imaging can be useful. If you are suspicious for a congenital anomaly an MRI might be helpful. Cysts, endometriomas are less common in the adolescent population than the adult population. However, can have obviously other types of cysts that can be detected on ultrasound or MRI and they are non-invasive tests to survey the pelvic anatomy.
Labs play a pretty limited role. Obviously any young woman of reproductive age coming in with pelvic pain gets a pregnancy test and a CBC if they are having some abnormal uterine bleeding.
So, basic work up and what next? I will typically initiate a trial of medical management, and I say a trial, a very short trial of approximately two to three months. The way we define chronic pelvic pain in the adult community is pain greater than six months or more but you can see how in this very young population that is not really a realistic approach, right, for the reasons we discussed. If they are not responding after two or three cycles then we talk about pursuing diagnostic laparoscopy, or, they might want to skip the medication and say, “I don’t want to start taking hormones for the next how many years. I’d rather, you know, get my diagnosis and then that’ll just help me prepare mentally and I can work from that”. So you can jump straight to a diagnostic laparoscopy as well.
I am not going to go too much into this because there is another talk all about this but first line treatments, as I said NSIADs and OCPs. You can use them cyclically where you still have your bleeding or continuously to suppress your menstruation. Progesterone only medications – remember that endometriosis is an estrogen driven disease. There is a decrease in the progesterone in the environment of these lesions. There is Norethindrone, Depot Provera and Mirena IUD. My drug of choice that I pretty much go to all the time is Norethindrone. I find it has the least number of side effects and you can essentially continue with it safely for quite a long time, and Lupron.
I just want to say a short word on Lupron. I find that a lot of patients come into my office and say, you know, they have been on Lupron and they are 20 something years old and they still have a long way to go before they really have this disease under control. We have to remember that this induces a menopausal type state. You can suffer from horrible vasomotor symptoms, hot flashes, vaginal dryness and mood issues. In adolescents the peak bone mass is reached by approximately 18 to 20 years old. You do not want to interfere with that and because it induces a hypo-estrogenic state it has an impact on bone loss and unlike Depot Provera this bone loss may be irreversible. I say there are other well tolerated, long term and effective options. I almost never use Lupron for this population.
Moving onto surgical management, this is slightly a misnomer because it is not just diagnostic laparoscopy. You have to remember it is diagnosis and possibly treatment. I want to emphasize that it is so important to refer to someone who is not just a specialist in pelvic pain or endometriosis but are also minimally invasive surgeons who will be able to take the steps necessary to excise all the endometriosis you see or as best as they can. As Dr. Seckin said, you do not know what you are going to get. You may see a lesion and it might look superficial and then it is actually a lot deeper or more serious than you had thought. You have to treat that appropriately you cannot peek and shriek and close and then recommend to someone who you think be a more advanced surgeon.
Most adolescents have stage one and two disease. Again, the severity of the disease does not correlate with pain levels. The only time I refer to this stage of endometriosis is really to say stage four disease, which is just to imply the severity of involvement. This is when basically you have a block of concrete in your pelvis because of all the fibrosis and adhesions and the disease. But aside from that I do not routinely stage my diseases.
Red and clear lesions are more common so I just wanted to go through some of these pictures. These are more common in adult women. These are your classic blueberry type, dark brown spot lesions surrounded by this white-ish tissue that is some fibrosis and scarring. And here, this is the back of the uterus, this is called the uterosacral ligament and you can just see a whiting out. You can see how these things may look normal to some people who are not used to seeing all the different variations of endometriosis. Here, down in the bottom you see this area this is a peritoneal fold, it can be created by fibrosis and endometriosis, and you can find implants within that. Here are more clear lesions. These are clear lesions, how many of you can actually see these lesions here? They are pretty much invisible but someone who is skilled with that can detect it right away. And these are more vesicular lesions here on the bowel. These are your classic adolescent red lesions and are more kind of powder burn type lesions.
Post-operative management: in the adult population the role of post-operative medical management is not always advocated. It is not necessary I should say but we do not have all that information in the pediatric population. There are some studies that suggest the combined surgical medical approach may decrease disease progression but as we discussed we do not really know the natural course of this disease and you want to closely monitor for recurrence and persistence of symptoms.
A word about repeat laparoscopies; it is important to recognize that doing an immediate repeat laparoscopy or even within a year unless the reason was that you as a provider really feel that whoever did the previous laparoscopy may have missed a lot of the lesions or the provider asked that “You know, I didn’t feel comfortable with this. I certainly left a lot of disease inside”, but if you yourself performed the excision and are confident about it and comfortable about it the utility for going in again so soon after is pretty low.
This is a study, a retrospective study that came out of, I believe, Harvard. It involved 90 patients with pain after initial laparoscopy and medical treatment. They had already had one laparoscopy, they already had medical treatment and they are still in pain. These patients then were taken back for a second look and you would think, well, if their pain is worse or the same then maybe the endometriosis came back, or maybe now it is at a worse stage. And what they found is really even in these women the majority, 70 percent, had no change, almost 20 percent actually improved by a stage if we are just staging the endometriosis, and one percent even improved by two stages. Only ten percent of women who were taken back for a second look are actually worse in terms of stage.
The conclusion – my approach to early diagnosis of endometriosis is to identify the symptoms early, remember persistent/recurrent pain leading one to seek medical care is not normal. You can trial a short course of medical therapy. I would consider options other than Lupron. You want to refer to an endometriosis specialist who is able to both identify and excise the lesions and you want to continue to monitor closely for persistence and recurrence.
Thank you very much.