Endometriosis and its Misunderstood Etiology
Painful and chronic, endometriosis affects 10% of reproductive-age women, costs an estimated $69. 4 billion per year in excess health expenditures, and reduces workplace productivity by an average of 6.3 hours a week. These statistics — and recommendations for getting past them — are outlined in a 2019 report from the Society for Women’s Health Research (SWHR).1 The report was based on a roundtable-style dialogue consisting of leading clinicians, patients, and researchers, hosted by the nonprofit.
Women with endometriosis are more prone to autoimmune diseases like Lupus and more likely to develop cardiovascular disease. (Image: 123RF)
Current Guidelines and Approaches
Clinical guidelines for endometriosis, which have not been updated in 5 to 10 years, indicate that the current standard for definitively diagnosing the disease is laproscopic biopsy, an invasive and sometimes risky procedure, according to the report. Part of the challenge is that the etiology of endometriosis is not fully understood. For starters, its most common symptom — chronic pelvic pain — is not specific to endometriosis and may be caused by a variety of other conditions. In fact, many factors are considered to play a role in the disease’s pathogenesis (eg, genetics, immune dysfunction, inflammation) while some experts think it may be an amalgamation of disorders.
The simple fact is that no validated set of screening questions and no noninvasive diagnostic tool exists. As a result, nearly three-quarters of women with the condition are misdiagnosed, with many having to wait 7 to 12 years after the onset of pain symptoms to obtain an accurate diagnosis. This delay may not only degrade the patient–provider relationship but may also lead to long-term physical and emotional damage, according to the report.
When a diagnosis is finally made, the treatment options — including, in general, NSAIDs, hormones, and surgical removal — are limited. Approximately 11 to 19% of women with endometriosis report no improvement in pain with medical therapy and recurrent pain is common after treatment cessation. In addition, the available therapies (eg, combined hormonal contraceptives, progestins, gonadotropin-releasing hormone agonists and antagonists) may produce significant side effects and are not viable when a patient is pregnant or trying to get pregnant.
Another major barrier to assessing and treating this disease regards clinical training around the condition. According to SWHR, half of the healthcare providers surveyed could not name three of the main symptoms of endometriosis. The report also discussed serious obstacles in access to treatment.
Endometriosis as a Catch-All Woman’s Disease: What HCPs Need to Know according to Sawsan As-Sanie, MD, MPH
Looking ahead, the Society for Women’s Health Research recommends more funding and research be dedicated to understanding the underlying biology of endometriosis and its subtypes in hopes of finding new therapeutic avenues. To get into the specifics, PPM Editor Angie Drakulich spoke to Sawsan As-Sanie, MD, MPH, lead author of the SWHR’s report.1 Dr. As-Sanie serves as the director of the University of Michigan Endometriosis Center and an associate professor and director of the Minimally Invasive Gynecology Division and Fellowship in the university’s Department of Obstetrics and Gynecology. She is also a member of the SWHR Network on Endometriosis and Fibroids.
PPM: Why do you think there is such a lack of understanding and funding for researching endometriosis, despite its significant impact on the population and healthcare costs? Do you think it simply falls under the general “it’s a women’s issue so it’s less important” umbrella?
Dr. As-Sanie: Endometriosis is under-recognized by both patients and healthcare providers (HCPs). For women, their pain is often normalized and minimized — sometimes by themselves, by their family and friends, and by society. They are told that having painful periods, a cardinal symptom of endometriosis, is something that all women deal with and so many women do not discuss it with their doctor, assuming that this is normal. From the perspective of the provider, our training in the evaluation and management of chronic pain, including chronic pelvic pain, is very limited. Many HCPs are not adequately trained in this area.
Providers are also guilty of minimizing women’s pain due to implicit gender bias in the evaluation and management of pain in women. In fact, chronic pain in adolescent and adult women is more likely to be dismissed or minimized by clinicians across a range of specialties. Furthermore, research on women’s health conditions — particularly reproductive health conditions — has historically been underfunded. These factors all contribute to underfunding research on endometriosis and chronic pelvic pain, resulting in our limited understanding of this disease.
PPM: The SWHR report notes that comorbidities are highly prevalent in endometriosis patients. What types of comorbidities are most common?
Dr. As-Sanie: Some of the most common comorbidities for women with endometriosis are other chronic pain conditions. It’s common for these women to have overlapping conditions that cause chronic pelvic pain, such as irritable bowel syndrome, bladder pain syndrome (previously named interstitial cystitis), and pelvic floor myalgia. They are also more likely to have pain in other areas of the body, such as with migraine or tension headaches, fibromyalgia, chronic fatigue syndrome, vulvodynia, temporomandibular disorder, and chronic low back pain. Increasing evidence suggests that these conditions, which are a part of a cluster of 10 chronic overlapping pain conditions, share an underlying dysregulation of the neurological, endocrine, and immune systems — which are frequently associated with fatigue, sleep, mood, and cognitive symptoms (such as memory difficulties).
We also know that women with endometriosis are more prone to autoimmune diseases like Lupus and also more likely to develop cardiovascular disease. While the links between these conditions are not completely clear, one theory is that since endometriosis is associated with both pelvic and systemic inflammation, that this underlying inflammation predisposes women to develop some of these other conditions.
PPM: As noted herein, the SWHR cited that half of general HCPs surveyed could not name three of the main symptoms of endometriosis. As more primary care providers (PCPs) are assessing for and managing pain conditions, versus a specialist, what do you recommend? Is this a matter of redesigning medical school curricula or expanding CME to include sex-specific conditions?
Dr. As-Sanie: All of the above. We need to greatly improve our training in the evaluation and management of chronic pain, especially in women, starting from the earliest and most fundamental levels of education from medical and nursing school curriculum to residency and postgraduate training across all disciplines, not just obstetrician-gynecologists. We also need to target the HCPs who are already out there treating these women with education and training through lectures at healthcare conferences, online CME, and journal articles. All these tools are very important and likely to help reach diverse groups of providers across all disciplines.
PPM: The statistics around misdiagnosis and delayed diagnosis for endometriosis are quite frightening, especially from a patient’s perspective. This may be particularly important for young women and teens experiencing symptoms — the SWHR report suggests there may be a hesitation around undergoing a pelvic exam and/or an invasive diagnostic procedure at this age. Are you aware of any validated, noninvasive tools or tests in the works that may give patients hope?
Dr. As-Sanie: There are currently no validated nonsurgical methods for diagnosing endometriosis, though this is a huge area of interest in the clinical and research community. Researchers are looking for ways to conduct noninvasive diagnosis by analyzing a patient’s blood, for example, but there is nothing on the market yet that reliably replaces surgery. However, trained HCPs are becoming increasingly accurate at diagnosing a woman through evaluating her history of symptoms, a physical exam, and targeted imaging, such as ultrasound and occasionally MRI. It’s not perfect, but many of the treatments that we recommend are safe and appropriate to use for those with suspected endometriosis, without the need for the patient to undergo surgery before treatment.
PPM: Many clinical studies and reports conclude by recommending a patient-centric, multidisciplinary approach. How can clinicians truly put this into practice given their limited schedules and the lack of validated tools for this condition in particular?
Dr. As-Sanie: Multidisciplinary treatment strategies such as those recommended in the SWHR report are critical for patients with complex pain problems that are refractory to the usual treatments. However, many women with pelvic pain can be safely and effectively treated by their PCP, if that doctor has the knowledge, compassion, and willingness to spend time with them. PCPs need to screen their patients for pelvic pain symptoms at their annual check-up and then bring them back for further evaluation and counseling if needed. PCPs should have the skillset to initiate first-line therapies and recognize red flags so that they can recommend those patients who fail the first-line therapies to specialized, multidisciplinary clinics.
PPM: Could robotic surgery offer a revolutionary change for treating women with endometriosis?
Dr. As-Sanie: Robotic surgery is one form of laparoscopy, which is a minimally invasive surgery used to locate and remove endometrial lesions. But what’s more critical than the type of laparoscopy is that the surgeon performing the procedure has specialized training and experience in treating all forms of endometriosis — from superficial to deeply infiltrating — in a single surgery. There is no distinct advantage to the surgery being done robotically as compared to traditionally because these are all just tools dependent on the training and experience of the surgeon.
Unfortunately, there is no standardized criteria or certification for endometriosis surgery and most physicians that complete a general OB/GYN residency simply do not get enough training in more complex endometriosis cases. Among the different types of gynecologic surgeries, endometriosis surgery (especially for deeply infiltrating endometriosis) is one of the most complex and risky procedures we do. It’s sometimes just as complex as surgery for cancer. The surgeon must have the knowledge and skills to fully evaluate the patient and then execute the right surgery for the right patient in a single procedure. It’s far better to have one good surgery then multiple surgeries that don’t adequately address the problem.
It is also important for patients and providers to recognize that not every patient needs surgery, and when surgery is indicated, even the best surgery is not always curative for every patient. While surgery can help most women, it does not help all. Even among women who get initial relief in their symptoms, pain may recur months to years later, and it does not always correlate with recurrent endometriosis lesions. So, in addition to performing the right surgery at the right time, every patient deserves a comprehensive evaluation and treatment plan that incorporates the appropriate medical, behavioral and interventional treatment options that address all conditions that are contributing to her pain and other symptoms that reduce her quality of life.
-Reported by Steven Aliano, Q&A by Angie Drakulich