© Center for Endometriosis Care/Ken Sinervo MD, MSc, FRCSC. All rights reserved. No reproduction permitted without written permission. Revised since original publication and current as of 2024. No external funding was utilized in the creation of this material. The Center for Endometriosis Care neither endorses nor has affiliation with any resources cited herein. The following material is for informational purposes only and does not constitute medical advice.

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 (primarily around the time of menstruation)? Endometriosis may be at the root of all of these symptoms – and many others, as the disease can present in different ways for different individuals. Most often, however, “pain” is among the top subjective complaints. Symptoms may routinely occur far and apart from menses - and in those who do not menstruate - at any time of the cycle. It is also entirely possible for post-hysterectomy or post-menopausal individuals to have painful endometriosis. The disease has also been found in individuals assigned male at birth, not all of whom were on estrogen therapy. Yet despite being among the most common of diseases, persistent myths, misinformation and deficient health literacy continue to surround the disease, often resulting in poor information and continued lack of care. So - what IS endometriosis?

The scientific literature defines endometriosis as “a systemic, inflammatory disease characterized at surgery by the presence of endometrium-like tissue found outside the uterus, usually with an associated inflammatory process. It is a spectrum disease with a variety of subtypes and clinical presentations, and pain, inflammation, infertility, development of endometriomas (“chocolate cysts”), fibrosis, formation of adhesions (fibrous bands of dense tissue), GI and other organ dysfunction, and much more are common with endometriosis” (Int’l Endometriosis Working Group, 2021). In lay terms, this means: a disease characterized by tissue resembling the native endometrium found elsewhere in the body. It’s important to understand that though the tissues are similar, however, they are not identical. Endometriosis is not a ‘uterine disease’ - it is a bodywide condition which has been found in virtually every organ system. As Yale researchers have noted, “endometriosis goes far beyond the pelvis.” The aberrant processes involved in the disease give rise to pain, inflammation, development of endometriomas (“chocolate cysts”), fibrosis, formation of adhesions (fibrous bands of dense tissue), organ dysfunction and much 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.

Endometriosis is not merely a “period disease” or a “condition of menstruation” as it is often mislabeled in public discourse. While menstrual problems may be a large symptom of endometriosis for some, it is not simply ‘a menstrual disorder’ - which implies it only affects people during menstruation, only impacts the reproductive organs, and can be easily resolved through cessation of menses - none of which are true. Minor cramping during menstruation is not uncommon for many individuals, particularly adolescents. Inflammatory hormones i.e., prostaglandins are linked to menstrual discomfort; this mild-moderate 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.

WHAT IT FEELS LIKE
Not all individuals with endometriosis will have all symptoms or comorbidities, of course, and no two cases are identical. Common symptoms include (but are certainly 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 links to adverse obstetrical outcomes i.e., preterm birth
* 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

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. 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.

HOW IT OCCURS
We still don’t know! The origins of the disease range from concepts like cellular metaplasia, which according to the World Health Organization is “when cells outside the uterus change into endometrial-like cells and start to grow,” to embryonic cell rest, implantation and others. Accurately termed by many as a “disease of theories,” the definitive cause(s) remain under heavy debate, though demonstrated association with a number of hereditary, environmental, epigenetic and even certain menstrual characteristics may exist. Research implicates HOX genes, mesenchymal stem cells and certain immunologic factors in its origins; 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 the 1920s, is perhaps the most popular and enduring of theories. However, it is not without shortcomings and is often challenged in the literature. Initially, Dr John Sampson held that endometriosis was the result of “seedlings” from the ovaries.  Later, in 1927, he proposed the disease results from reflux menstruation, wherein normal endometrium is simply “showered backwards” onto the peritoneum and ovaries, taking hold and implanting. However – endometriosis lesions and the normal endometrium are NOT histologically identical - something Sampson himself acknowledged, and retrograde menstruation is a very common phenomenon among most menstruators, yet not all will develop endometriosis. Essentially, Sampson’s Theory considered endometriosis as otherwise normal endometrial cells which behave abnormally because of abnormal peritoneal milieu; however, this is often critiqued in the current literature. Multiple studies have demonstrated that retrograde menstruation cannot wholly account for the development of endometriosis, moreover, that the eutopic and ectopic endometrial stromal cells in those with the disease exhibit fundamental differences in invasive, adhesive, and proliferative behaviors from those who do not have the disease. Contrary to popular public doctrine, while the tissues do resemble each other, they are not identical. As such, there are various additional factors that must contribute to disease pathophysiology and pathogenesis which simply cannot be explained by retrograde menses alone.

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 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.

Again, despite the myriad of theories, no single assumption accounts for all cases in all those affected. It may be that affected individuals are born with endometriosis and a combined number of multiple factors subsequently trigger the disease. However, we do know that endometriosis is not just ‘painful periods’ - nor can it be induced simply by rogue bits of wholly normal/native endometrium implanted in abnormal places, caused by backflow menstruation alone.

In addition, endometriosis is certainly ‘not in your head’ – though a number of sources have implied 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 may be present in some with endometriosis according to the data, 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 or otherwise rooted in emotions leads only to further delayed diagnosis and ineffective treatments and should be denounced wherever such claims appear.

WHO “GETS” ENDOMETRIOSIS
Generally, no particular demographic, personality trait or ethnic predilection exist in association with endometriosis and there is no preventive measure, though at least one (now retracted) debatable phenotype study attempted to link certain physical characteristics as to 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. 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 individuals of reproductive age, the disease can and does impact adolescents, menstruators and non-menstruators of all races – including 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. For example, it is important to recognize that while the disease is traditionally associated with cisgender women, endometriosis should also “be recognized as a significant issue for transgender men.” The often 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. As we have stated for decades, the time for the disease to receive recognition as a major public health issue is long past due.

WHERE IT IS
Often found in the pelvic cavity, endometriosis can also be present in distant locations like the lungs. Unfortunately, misinformation persists, and its far-reaching, systemic effects often go unrecognized.

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. Endometriosis can also be diagnosed in areas outside the reproductive organs i.e., diaphragm and lungs, where it can induce 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 spleen, 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 13,000 procedures across a span of 30+ years, we have never encountered brain endometriosis in our practice.

There are also scant reports in the literature of vena cava invasion in a post-menopausal patient; on the adrenal gland; periclitoral endometriosis; the iliac vein; intrahepactic endometriosis; nasal endometriosis; and many, many other uncommon/rare manifestations of the disease.

HOW IT IS DIAGNOSED
The only way to obtain biopsy-proven confirmation of the disease is through surgical pathology; this typically means via the minimally invasive procedure known as Laparoscopy. The disease should be treated at the time of diagnosis.

Though symptoms and/or diagnostic testing (CT scans, MRIs, etc.) may give rise to highly informed suspicion and are very helpful for presurgical planning in particular, they do not rule out the disease definitively. Imaging is also not a “treatment” for endometriosis; it is a tool lending towards diagnosis. Only surgery permits the visual and histological diagnosis of the lesions. Most importantly, Laparoscopy also facilitates actual treatment of the disease in the same encounter.  It is as yet impossible to confirm a diagnosis of 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. To date no biomarkers can diagnose or rule out endometriosis/adenomyosis with high certainty and there are no blood tests or diagnostic biomarkers that can be used to universally diagnose endometriosis as of this writing, but this remains a robust area of research.

ENDOMETRIOSIS STAGING
ASRM stages I-minimal, II-mild, III-moderate, or IV-severe
There are several staging systems used, ranging from ASRM to AAGL to the Enzian. While most common, the ASRM stage criteria does not correlate well with the severity of symptoms and a better system sorely is needed. The AAGL Classification is somewhat more advanced, in that it better discriminates surgical complexity. Stage, in general, however, has no real bearing on lived experience and symptomology of the disease to the affected individual.

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/painful bladder syndrome, 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. Recently, an association between laparoscopically proven endometriosis and future stroke has been discovered (though it is important to note that mediating effects i.e., hysterectomy, oophorectomy need further investigation).

Endometriosis & Malignancy: in the past decade, a potential cancer risk in association with the disease has emerged. 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. Nonetheless, much research remains to be done to better illustrate and understand the tenuous link between endometriosis, ovarian cancer and other potential malignancies.

ENDOMETRIOSIS IS A PRIORITY PUBLIC HEALTH BURDEN
Endometriosis affects approximately 190 million individuals worldwide (7.5 million in just the U.S. and 775,000 in Canada alone) at estimated costs in the USA nearing $70 billion annually. 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 its socioeconomic and global health impact, it remains a poorly understood, underdiagnosed, undertreated disease, sorely lacking in awareness, research funding and validation. This continues to lead to delayed diagnoses, poor treatments and widespread lack of support. We have called for over a decade to classify endometriosis as a priority public health concern.

TREATMENT OPTIONS
There is no prevention or universal cure for endometriosis, and symptoms may become chronic for some. Many patients will need complex, multidisciplinary surgery combined with adaptation of other adjuncts and potentially even lifestyle changes; indeed, we believe in an integrated, patient-centered approach. Unfortunately, delayed diagnosis and poor management are common, with many patients suffering through repeated, ineffective (non-excisional) surgeries and inadequate therapies.

It is important to understand that no two cases of endometriosis are the same and thus may not respond to the same treatment approaches the same way. Still, poor treatments lead to poor outcomes, and 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 actually removed, or through long-term use of painkillers, and/or via medical therapies like GnRH agonists/antagonists, oral contraceptives or other hormonal suppressives, but these only manage - or mask - symptoms and do not actually treat the disease long-term. Use of medical therapy - and every single treatment for the disease including surgery - should be decided upon by the patient themselves after being carefully counseled through the process of truly informed consent. A combination of therapies may be necessary.

Patients may also sometimes be misled to believe that the only long-term solution is removal of reproductive organs (hysterectomy/salpingo-oophorectomy). Hysterectomy has a place in endometriosis treatment, but the disease is not “cured” by removal of the uterus, ovaries and/or tubes and cervix.  This ongoing misconception is responsible for countless, sometimes possibly 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.

Still – despite often stark outlook on the disease, there is always hope!

Quality surgery, alternative therapies, diet and nutrition, acupuncture, physical therapy and many other adjunct treatments including medical management for some individuals can all be helpful at effectively reducing symptoms long term. As a multidisciplinary disease, we believe high-quality, minimally invasive excision (LAPEX) is the operative - surgical - cornerstone of any effective, integrative management plan that involves surgery. While excision is not a universal, definitive cure, it can be an important component of endometriosis 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.  For example: a 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 obstetrics or general gyn at all here at the CEC, and we concentrate only on surgical excision of endometriosis and associated gynepathologies.

At the CEC, we use the C02 laser as an effective cutting 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/persistence.

Understanding that surgery may not be indicated or right for every endometriosis patient and is not a universal guarantee of relief, when surgery is performed, LAPEX is a surgical treatment that can alleviate many of the associated symptoms. However, excision is practiced by only select advanced gynecologic-endoscopic surgeons. 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. Unfortunately, access to excisional centers of expertise can have multiple barriers for many due to the structure of the healthcare system. Our Center has been part of the decades-long effort to try and remove such barriers and will continue to strive for such changes.

THE FUTURE OF ENDOMETRIOSIS
Individual accounts of life with endometriosis often exemplify and embody the social implications of negative attitudes towards menstruation and reproductive health in general. 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 health initiative needing further promotion, understanding, research and empathy. Only through early intervention can we reduce the associated morbidity, infertility and progressive symptoms of endometriosis. Early diagnosis and proper treatment are critical keys to living well in spite of the disease.

Though it may not seem so, there are many committed researchers who have dedicated their lives to advancing understanding of the disease. Non-invasive technologies represent the leading areas of study, and the CEC is pleased to be a part of such research efforts as a principal investigator site. Some legislators are also recognizing endometriosis as a public health crisis and have formed working groups to pass formal legislation towards increased research funding, improved access to quality care, and better support of those with the disease. While much remains unknown about endometriosis and there is no absolute/universal approach that will help every patient, we are hopeful for continued progress.

CAN WE HELP YOU OR A LOVED ONE?
Not everyone is a candidate for excision surgery, and not everyone will benefit from it; however, if you would like to consider care at our Center and determine if we can help, please visit: https://centerforendo.com/thinking-about-becoming-a-patient