Endometriosis: an old problem without a current solution

The painful symptoms of endometriosis were described as early as 1690 1, but more than 300 years later there is still no definitive treatment or prevention for a disease that affects an estimated 6–10% of women of reproductive-age 2. This equates to 176 million women worldwide 3, whose lives are burdened daily by pain and/or subfertility. From a medical perspective, endometriosis is defined as an inflammatory condition characterized by lesions of endometrial-like tissue outside the uterus and is associated with pelvic pain and subfertility 2, 3. “In its worst stages, this disease affects the well-being of the female patient totally and adversely, her whole spirit is broken, and yet she lives in fear of still more symptoms such as further pain …”. These are the words of Louis Brotherson MD, written in 1776 1. They accurately describe what many women with endometriosis experience today. From a societal perspective, endometriosis carries an annual financial burden estimated at €9579 per woman affected (based on a multicenter study in 10 countries), with decreased quality of life as the most important predictor of direct healthcare and total costs 7. What is noteworthy in these calculations is that actual treatment costs account for only one-third of this amount: two-thirds of this cost to society is due to a loss of productivity because of painful symptoms 5, 7. Women with endometriosis are limited by their painful symptoms in their daily lives. We should aim to change this. However, for a woman to be diagnosed with, and consequently treated for, endometriosis we are dependent on the curiosity of the surgeon and the pathologist. Unfortunately, even if their combined sleuthing leads to a diagnosis, treatment of endometriosis is hampered by a limited armamentarium of medical treatments, which are all associated with variable side effects and effectiveness 3, as well as limited access to sufficiently skilled surgical care. Why is this? Why is medical care for women with endometriosis so hit and miss? We can fob this off on women's health being given low priority, in which there is quite a lot of truth, but it may also be because endometriosis, just like breast cancer, is indeed a disease of multiple subtypes – each subtype potentially responding differently to medical and/or surgical treatment. If so, these specific subtypes of endometriosis are yet to be discovered and potential targeted treatments have not been developed. To discover such potential disease subtypes requires data: a lot of consistent, comparable, reproducible data. In response to research priorities set out by a global consortium of investigators in endometriosis 8, the World Endometriosis Research Foundation (WERF) has developed landmark tools to facilitate the advancement of endometriosis research by enabling the collection and analysis of comprehensive and powerful data that are as homogeneous as possible 9. This may finally provide us with a better understanding of the causes and/or triggers of different types of endometriosis, potential novel diagnostic methods, and better (targeted) treatment(s). The WERF EPHect standardized surgical form 10 together with the clinical form 11, which captures both demographic and descriptive data, aim to discover comprehensive phenotypic description of specific endometriosis symptomatology and potentially confounding symptoms to facilitate collaboration and pooling of individual participant data across research centers to enable large sample sizes, and to allow subgroup analyses with adequate statistical power. Combining this surgical and clinical data collection with standard operating procedures for biological fluid and tissue sample collection, processing, and long-term storage, will enable accurate and reproducible molecular phenomic, metabolomic, and genomic investigations 12, 13. Big data may help endometriosis disease discovery. The question, therefore, that women with endometriosis have, is: are you going to be part of the solution? The development of targeted treatments for endometriosis may reduce the burden of endometriosis for millions of women across the globe by eliminating pain, preserving fertility, improving quality of life, and reducing socio-economic costs. The economic burden associated with endometriosis is similar to other chronic diseases such as diabetes, Crohn disease, and rheumatoid arthritis 7. Yet we see no comparable investment in disease discovery for endometriosis. We need to change this! We can change this by collaborating globally. We can change this by coordinating research and using comparable tools. We can change this by keeping our minds open and inquisitive. We must apply all of our faculties to improve the lives of women with endometriosis. Please be part of the solution: let's work together to eliminate the burden of endometriosis in future generations of women. Endometriosis is one of the most common gynecological diseases, affecting 6–10% of all women of reproductive age. Endometriosis can affect everyone regardless of their ethnic origin, economic and social background. It is defined as an estrogen-dependent inflammatory condition characterized by lesions of endometrial-like tissue outside of the uterus and is associated with pelvic pain and subfertitlity 1-3. Endometriosis is caused by cells similar to the uterine lining (endometrium) that are outside the womb and get stuck in the wrong places in the body, mainly on abdominal organs (ovaries, fallopian tubes, uterus surface, the area between the uterus and rectum known as pouch of Douglas, uterosacral ligament, bladder, peritoneum and intestine). These endometrial cells begin to grow, become encapsulated by the body's defense mechanisms and form cysts and lesions (endometriosis) which cause inflammation in the abdomen that can cause abdominal pain, scar tissue and adhesions. In rare cases, endometriosis can also be found in places in the body such as the lungs and when it grows inside the uterine wall it is called adenomyosis. Endometriosis can be divided into different stages, from mild endometriosis with isolated foci to severe endometriosis with large continuous sheets of endometriosis that can affect other organs such as the intestines and the bladder. It is important to remember that the symptoms do not always correspond with the degree of endometriosis. The reasons for developing the condition remain unknown and views differ as to its inflammatory or autoimmune nature 4. Risk is highly influenced by genetic factors. Symptoms are individual and will often relapse and change over time, for example, from having lasted a few days a month to several months at a time or all the time. It is important for those affected that they receive help and support through all stages of life as the disease can persist after a treatment. It takes an average of seven to eight years from the time women come to realize they are in more pain than normal until they get diagnosed with endometriosis, often having sought help from several different doctors. Many affected by endometriosis have wrongly been diagnosed with urinary tract infection (UTI) or irritable bowel syndrome (IBS) 5. Definitive diagnosis of endometriosis is by visualization or biopsy after excision of lesions via laparoscopy. While there is no known cure for endometriosis, effective treatments, albeit often with side effects, do exist 3. These include medication with nonsteroidal anti-inflammatory drugs (NSAIDS) and opioids for pain relief, hormone therapy, surgery to remove lesions and scar tissue, hysterectomy and removal of the ovaries. Pregnancy alleviates symptoms for some, and most women affected become better or completely symptom free after menopause. Despite research, knowledge is still lacking on many aspects of this multifaceted condition. Recommendations point to several new areas of priority, including patient stratification, epigenetics, and research in low income countries, along with the need to broaden multidisciplinary approaches to understanding and treating endometriosis 4. Fact sheet compiled by Maya Acharya and Susana Benedet.