© Center for Endometriosis Care. All rights reserved. No reproduction permitted without prior permission.
Original publication: 2008. Last update: 2019.
A Challenging Conundrum: non-menstrual abdominal or pelvic pain? Infertility? Painful sex? “IBS” or bowel-related symptoms? Bladder pain or dysfunction? Lower back or leg pain? Bloating? Crippling fatigue? Debilitating periods? Lung collapse around the time of menstruation? Endometriosis could be at the root of all of these symptoms – and many others, as the disease may present in different ways in different individuals. Most often, however, “pain” is among the top subjective complaints of those struggling with endometriosis.
Despite being among the most common of diseases, persistent myths, misinformation and deficient health literacy continue to enshroud the disease – even by the well-intentioned sources – often resulting in poor information systems and continued lack of effective care.
Endometriosis is much more than simple, so-called “killer cramps,” as it is often mistakenly labeled, with symptoms routinely occurring apart from menses at any time of the cycle and, in many instances, becoming chronic in nature. It is important to understand that minor cramping during menstruation is not uncommon for many individuals, particularly adolescents. Inflammatory hormones like prostaglandins (along with others) are linked to menstrual discomfort; this mild pain is not typically cause for alarm and may be remedied through a variety of measures. Usually, such pain is temporary and subsides after menses. This is called “dysmenorrhea.” Dysmenorrhea is NOT the same as endometriosis.
Endometriosis is not just ‘painful periods’ nor is it simply ‘bits of normal endometrium implanted in abnormal places, caused by backflow menstruation’ as many articles, the media, endometriosis foundations, spokespersons and even some scientists continue to incorrectly describe. Endometrium – the lining of the womb which breaks down and is shed during menstruation – is histologically different from the functional glands and stroma that comprise endometriosis. Contrary to popular public doctrine, while the tissue does somewhat resemble – it is not identical to – the native endometrium.
Characterized as the presence of endometrial-like tissue found in extrauterine sites – an important distinction! – the aberrant processes involved in endometriosis give rise to pain, inflammation, development of endometriomas (“chocolate cysts”), fibrosis, formation of adhesions (fibrous bands of dense tissue), organ dysfunction and more. Alterations in certain biological processes of the endocrine and immune systems have also been observed with the disease, and endometriosis is embodied by a complexity of multiple immunologic abnormalities, endocrine alterations and unusual expression of adhesion molecules.
Who ‘gets’ endometriosis? It is likely that a multitude of factors including genetic/epigenetic predispositions play strong roles in determining which, when and whether an individual will develop the disease. Though endometriosis largely affects females of reproductive age, the disease can and does impact menstruators and non-menstruators alike – including rare cis males, post-hysterectomy/menopause and before menarche. It is also imperative to look beyond gendered health and include all persons, many of whom who are often struggling to access endometriosis diagnosis, treatment and supportive, quality care in a traditionally female-identified space. The oft-overlooked, unique considerations in healthcare settings that fail to be inclusive can lead to additional stressors, further isolation and impaired treatments. Endometriosis has also been documented in the human fetus, and is extremely common in teens – though often dismissed, ignored and under-diagnosed due to stigma and lack of awareness. Without a doubt: endometriosis has a significant social and psychological impact on the diverse population affected – across several domains of their lives. The time for the disease to receive recognition as a major public health issue is long past due.
What it feels like: common, oft-debilitating symptoms of, and potential associations with, endometriosis include (but are not limited to):
* Crippling period pain in people who menstruate
* Abdominopelvic pain at any time, often intractable and chronic (meaning 6 months or longer of non-menstrual pelvic pain)
* Bowel or urinary disorders/pain/dysfunction
* Painful intercourse/penetration/sexual activity
*Pain with tampon insertion/inability to use tampons due to pain
* Infertility/pregnancy loss/possible link to preterm births
* Possible immune-related and other comorbid disorders
* Allergies, migraines or fatigue in some; may tend to worsen around menses
* Coughing up blood in cases of pleural/thoracic endometriosis
*Leg and lower back pain, particularly in cases of sciatic endometriosis
*The disease may also resemble some symptoms of, and has been linked to, adenomyosis
*Data also links chronic fatigue with menstrual abnormalities, endometriosis, pelvic pain, hysterectomy, and early/surgical menopause in some patients
*Comorbid pain syndromes, mood conditions and asthma have been documented in some individuals with endometriosis
Not all persons with endometriosis will have all symptoms or comorbidities, of course, and no two cases are identical.
Where it is: the disease may present at an early age and typically develops on the pelvic structures including the rectovaginal cul de sac, peritoneum, bladder, bowels, intestines, ovaries and fallopian tubes. However, endometriosis is also often diagnosed in areas outside the reproductive organs i.e. diaphragm and lungs, where it can induce a dangerous condition called Catamenial Pneumothorax. “Pelvic endometriosis” is traditionally defined as lesions of the tubes, ovaries and local peritoneum; “extrapelvic disease” is wide-ranging and refers to that found elsewhere – including the gastrointestinal tract, urinary tract, pulmonary system, extremities, skin, central nervous system and beyond. Rarely, endometriosis may be diagnosed even in areas as far removed from the abdominopelvic region as the brain and soleus/gastrocnemius muscles – though again, this is highly uncommon – indeed, in performing over 8,000 procedures across a span of 25+ years, we have never encountered brain endometriosis in our practice. There are also highly uncommon, sparse reports in the literature of vena cava invasion in a post-menopausal woman; on the adrenal gland; periclitoral endometriosis; the iliac vein; intrahepactic endometriosis; nasal endometriosis; and other very rare manifestations of the disease. Symptoms often start early in life, but may be ignored by caregivers, healthcare consumers and practitioners alike. An estimated 70% of teens with pelvic pain go on to be later diagnosed with endometriosis.
The pain and symptoms may worsen or even become chronic over time as the lesions become deeper and more fibrotic. As a result, infertility, bladder or bowel dysfunction, painful sex and many other physical and quality of life issues can occur. Current research indicates there is a preponderance of inflammatory milieu and hyperinnervation involved in the pathophysiology of pain in those with the disease, and that patients with chronic pelvic pain routinely demonstrate increased pain sensitivity even in non-pelvic sites. Early data implies that where the lesion is located may correspond to infiltration and/or adhesion formation, though further research needs to be done in this area.
Endometriosis & Malignancy: in recent years, a potential cancer risk in association with the disease has emerged, but it is critical to understand that endometriosis is not a malignancy. Increased risk factors include early-stage/low-grade disease and a specific histology i.e. endometrioid or clear cell carcinoma, but much is still unknown about the relationship. To that end, robust research is underway to evaluate the clinicopathologic characteristics of endometriosis-associated ovarian cancer (EAOC) in comparison with non-EAOC as well as other potential links. It is also true the potential exists for endometriosis to malignantly transform, but this again is a poorly understood and uncommon phenomenon. Though some mistakenly refer to the disease as a “benign cancer,” it is not: all cancers by definition are malignant. It is inaccurate to refer to endometriosis as ‘cancer’ and doing so contributes to the spread of misinformation that continues to surround the disease. “Benign” does not in any way diminish the impact of endometriosis nor does it imply the disease has any less capacity to derail lives. Nonetheless, much research remains to be done to better illustrate and understand the tenuous link between endometriosis, ovarian cancer and other potential malignancies.
Endometriosis & Other Disorders: there has been extensive data over the past decades indicating endometriosis may be linked to select co-morbid conditions in some individuals with the disease as well, including but not limited to a low/modest association between certain pigmentary traits and melanoma; pain syndromes (interstitial cystitis, irritable bowel syndrome/inflammatory bowel disease, chronic headaches, chronic low back pain, vulvodynia, fibromyalgia, temporomandibular joint disease, chronic fatigue syndrome, etc.) as well as mood conditions (defined as depression and anxiety) and asthma; select infections and endocrine disorders; headaches and migraines; thyroid disease and others. Similarities in the clinical and epidemiological features of the associated disorders may be at the root of their co-morbidity, and further investigation is needed.
Predictability: generally, no particular demographic, personality trait or ethnic predilection exist in association with endometriosis and there is no preventive measure, though some provocative and debatable phenotype studies have begun investigating certain physical characteristics as part of the disease profile. Still, widespread lack of awareness and accurate disease understanding on the part of society – even by those affected – contributes in part to the average diagnostic delay of nearly a decade (6.7 years) across multiple physician consults—even today.
The Cost of an Enigmatic Public Health Concern: carrying a fiscal tag of nearly $119 billion annually, endometriosis affects approximately 176 million individuals worldwide (7.5 million in just the U.S. and 775,000 in Canada alone). The illness accounts for a significant loss of productivity – nearly 11 hours per individual per week; 38% more than for those with similar symptoms who do not have the disease. Endometriosis remains a leading cause of gynecologic hospitalization and hysterectomy (many performed needlessly) and can distort every aspect of the impacted person’s life. Yet despite it’s socioeconomic and global health impact, it remains a poorly understood, underdiagnosed, undertreated disease, sorely lacking in awareness and validation. This continues to lead to delayed diagnoses, poor treatments and widespread lack of support.
Diagnosis: despite the recent pharma-sponsored ‘call to action’ for the clinical (presumptive) diagnosis and medical suppression of unproven endometriosis, the only way to confirm a definitive diagnosis of endometriosis is still surgically; usually via the minimally invasive procedure known as Laparoscopy. Though symptoms and/or diagnostic testing (CT scans, MRIs, etc.) may give rise to “informed suspicion” and are helpful for presurgical planning, only surgery permits the requisite visual and histological (biopsy proven) diagnosis. Most importantly, Laparoscopy also facilitates actual treatment of the disease. It is inappropriate – and impossible – to diagnose endometriosis medically. There have also been over 50 biomarkers studied to date towards a non-invasive diagnosis, none with universal success. A more recent study indicated that concurrent measurements of CA125, syntaxin-5 and laminin-1 might be a somewhat useful, non-invasive test in the diagnosis and prediction of disease severity, but this has not been borne out in large, multicenter studies, and CA125 has been a historically poor predictor of endometriosis. There are no blood tests or diagnostic biomarkers that can be used to diagnose endometriosis at this time.
ASRM stages I-minimal, II-mild, III-moderate, or IV-severe
Stage does not correlate with severity of symptoms and a better system sorely is needed.
What causes endometriosis – and what doesn’t: often called a “disease of theories”, the definitive cause(s) of endometriosis remain under debate, though demonstrated association with a number of hereditary, environmental, epigenetic and even certain menstrual characteristics exist. Current research implicates HOX genes, mesenchymal stem cells and certain immunologic factors in disease origin; nonetheless, no single theory explains endometriosis all those affected; more likely, a composite of several mechanisms is involved. The most popular theories which have emerged over time include:
Retrograde menstruation – ‘Sampson’s Theory’, which dates back to 1921, is perhaps the most popular – yet flawed – of theories. Initially, Dr. John Sampson assumed that endometriosis is the result of “seedlings” from the ovaries. Later, in 1927, he proposed the disease results from reflux menstruation, wherein endometrium is “showered backwards” onto the peritoneum and ovaries, taking hold and implanting. However – endometriosis lesions and endometrium are NOT histologically identical, and retrograde menstruation is a very common phenomenon among most menstruators. Essentially, Sampson’s Theory considers endometriosis as normal endometrial cells which behave abnormally because of abnormal peritoneal milieu; however, this is not supported or borne out in the current literature, though this notion has persisted for almost a century. Unfortunately, this popular theory continues to complicate effective management and understanding of the disease today. Despite persistent propagation of Sampson’s Theory by countless sources, multiple studies have demonstrated that retrograde menstruation does not account for pathogenesis; the eutopic and ectopic endometrial stromal cells in those with endometriosis exhibit fundamental differences in invasive, adhesive, and proliferative behaviors from those who do not have the disease. Without question, there are various additional factors that contribute to disease pathophysiology and pathogenesis. Propagation of outdated myths and misinformation, and the continued research positioning of endometriosis as normal endometrium, keeps the disease mired in outdated concepts, hysterectomy, failed drug therapy and incomplete treatment.
Immunologic dysfunction – a “broken” immune system may allow for the disease to take hold and play a small role in lesion development – but this does not sufficiently explain the disease process to begin with. Some have characterized endometriosis as an autoimmune disease, but there is no robust evidence to support this. It may, however, be linked to several autoimmune disorders and share an underlying pathophysiology. More research is needed to explore this topic, but it is important to note that coexistence is not indicative of causality.
Homeobox genes – dysfunction of HOX genes may results in abnormal differentiation and migration of cells during embryonic formation of the female reproductive tract, giving rise later to endometriosis. The presence of endometriosis in fetuses strongly suggests an embryologic origin as suggested over 30 years ago by the leading researcher and excision pioneer, David B. Redwine, MD.
Stem Cells – have been linked to disease even in absence of menstruation; this would also account for the rare cases of documented male endometriosis. Work continues to emerge from this area of important research.
Genetics – increased risk of endometriosis may exist in those with a mother or relative with the disease.
Environmental Toxicants – pollutants (including a speculative link to dioxins, for which there remains conflicting evidence) have been hypothesized to induce certain cell changes, which in turn facilitate abnormal immune response allowing for the disease to take hold.
In specific, very limited cases the cause may be anatomic and/or due to neonatal uterine bleeding, but this remains speculative. Still more recent data is exploring endometriosis from a systems biology perspective (Griffith et. al. 2014), while others maintain the disease results (at least in part) from hormonal aberrations i.e. certain deficiencies and inappropriate activation of receptor signaling and resistance, DNA Methylation, and/or aberrant MicroRNA expression.
Lymphatic spread/Halban’s Theory suggests vascular or lymphatic dissemination, but little confirmation has been reached in this particular area of research.
Despite the myriad of theories, no single assumption accounts for all cases in all those affected. It is likely that affected individuals are born with endometriosis and a combined number of multiple factors subsequently trigger the disease later in life.
Nevertheless, endometriosis is certainly ‘not in your head’ – though a number of sources have indicated over the years that endometriosis is caused by “negative emotions” and various deep-seated psychological components. While there are various social, psychological and emotional aspects to any painful, chronic illness such as endometriosis, these are consequences of the disease – not the cause. Endometriosis has its origins in very real, very complex genetic and molecular underpinnings – not some abstract ‘rejection of one’s uterus’ or inability to get along with one’s parents, among other erroneous claims. Various psychoimmune interactions are present in those with endometriosis i.e. pronounced immunological shifts, manifested by imbalanced production of anti-inflammatory cytokines among other biologic responses – but these are part of the network of adaptive reactions associated with and perhaps because of it – not the origin of the disease. The highly offensive contention that endometriosis is a psychological ailment due to one’s internal failings or otherwise rooted in emotions leads only to further delayed diagnosis and ineffective treatment of the disease, and should be denounced wherever such claims appear.
Poor treatments lead to poor outcomes: unfortunately, many who struggle are often misdiagnosed and/or directed to “manage” the pain for years through repeat, superficial/incomplete surgeries in which all disease is not removed, or through use of painkillers, and/or via medical therapies like GnRH agonists/antagonists, oral contraceptives or other hormonal suppressives – but these only mask symptoms and do not treat disease long-term in any way. Patients are also sometimes misled to believe that the only long-term solution is removal of reproductive organs (hysterectomy/salpingo-oophorectomy) – a dangerous myth. Though hysterectomy has its place in endometriosis treatment for select cases, particularly where pain originates from the uterus, the disease is not “cured” by removal of the uterus, ovaries and/or tubes and cervix. This ongoing misconception is responsible for countless, needless hysterectomies performed each year – indeed, nearly half of the 400,000+ hysterectomies performed in the United States annually are the result of endometriosis. Similarly, “pregnancy” and/or “menopause” are often touted as curative, but such claims are equally untrue. Many patients will need complex, multidisciplinary surgery combined with adaptation of lifestyle changes; indeed, we believe in an integrated, patient-centered approach here at the CEC.
Individual accounts of life with endometriosis often exemplify and embody the social implications of negative attitudes towards menstruation and reproductive health. This disease is so much more than ‘painful periods’ – it has the propensity to take away so many choices – when and whether to engage in a fruitful, enjoyable sex life free of pain with a partner of one’s choosing, when or if to pursue fertility options, whether or not to undergo invasive and painful procedures, or to choose ineffective menstrual suppression and medications which alter the cycle, and much more. Likewise, endometriosis is consistently sidetracked by and mired in the fertility aspect by many researchers and physicians, when what we should be focusing on is not a person’s procreative potential, but the impact which pain has on the individual’s entire life and ability to make and enjoy one’s own choices – whether sexual or career or socially oriented. Truly, endometriosis is a public health crisis – and a key pelvic health initiative needing further promotion, understanding, research and empathy.
Still – despite often stark outlook on the disease, there is help and hope!
Quality surgery, alternative therapies, diet and nutrition, acupuncture, physical therapy and other adjunct treatments can all be helpful at effectively managing symptoms long term. We believe high-quality, minimally invasive excisional surgery (LAPEX) is the cornerstone of any effective management plan.
Surgical Treatment: confusion often surrounds the surgical approaches for endometriosis. It is important to understand that the laser is a tool – not a method of treating the disease. Likewise, Laparoscopy is the surgical approach (minimally invasive) – not a tool. The da Vinci robotic-assisted procedure is also an approach, not a method. It is important to understand that tool and method are not nearly as important as skill of the surgeon: if he or she cannot excise, they cannot excise using any method or tool. For example: laser can be used to safely and successfully perform laparoscopic resection (excision) of all disease, as we do – or it can be used to superficially and incompletely burn surface lesions, as most obgyns do. It’s imperative to determine which method your surgeon will be using and understand their disease knowledge, approach and expected outcome. Again: the tool is not as important as the skill of the surgeon who uses it, and most tools can be used to facilitate a number of surgical approaches. We do not practice any obstetrics at all here at the CEC, and we concentrate only on surgical excision of endometriosis and causes of pelvic pain.
At the CEC, we use the C02 laser as an effective tool to achieve deep excision. Dr. Albee was among the early and few pioneers to focus their work solely on treating endometriosis and pelvic pain pathology, a legacy carried forward by our surgeons today. He was an early adopter of the laser for excision in the late 1980s and today, many advanced excisionists have followed suit. “LAPEX”, as coined by Dr. Albee (Laparoscopic Excision), differs significantly from less meticulous laser/other surgical techniques including laser vaporization and electrocautery as commonly performed by many ObGyns. These methods destroy tissue, making microscopic evaluation impossible and leaving behind endometriosis “roots” – leading to high recurrence. LAPEX is indeed the gold standard for the definitive treatment of endometriosis and may alleviate many of the associated symptoms, but is practiced by only select advanced gynecologic-endoscopic surgeons in the world. Excision requires highly advanced surgical expertise and commands intense training on the part of the practitioner, as well as a complete and thorough (and accurate) understanding of endometriosis etiology, pathophysiology, sequela and far-reaching consequences. Read more here about LAPEX.
Only through early intervention can we reduce the associated morbidity, infertility and progressive symptoms of endometriosis. We must alleviate our culture of menstrual misinformation through timely and authoritative disease education – thus leading to reduced costs and most importantly, improved patient outcome. Early diagnosis and proper treatment are critical keys to living well in spite of the disease.