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Category Archives: Symptoms

3 years ago Symptoms No comment

Inflammatory markers and endometriosis (CRP and CA-125)

Endometriosis is an inflammatory disease, so a lot of people have questions about blood tests that look at inflammation. Remember, all these tests might be an indication of endometriosis, but they are very nonspecific. The only way to definitively diagnose endometriosis is through surgery. 

What is C-Reactive Protein (CRP)?

“C-reactive protein (CRP) is an acute inflammatory protein that increases up to 1,000-fold at sites of infection or inflammation….Having been traditionally utilized as a marker of infection and cardiovascular events, there is now growing evidence that CRP plays important roles in inflammatory processes and host responses to infection including the complement pathway, apoptosis, phagocytosis, nitric oxide (NO) release, and the production of cytokines, particularly interleukin-6 and tumor necrosis factor-α….There are many factors that can alter baseline CRP levels including age, gender, smoking status, weight, lipid levels, and blood pressure (13). The average levels of CRP in serum in a healthy Caucasian is around 0.8 mg/L, but this baseline can vary greatly in individuals due to other factors, including polymorphisms in the CRP gene (14)…. C-reactive protein levels are known to increase dramatically in response to injury, infection, and inflammation (Figure  1). CRP is mainly classed as an acute marker of inflammation, but research is starting to indicate important roles that CRP plays in inflammation.”

So what does this have to do with endometriosis?

Endometriosis is an inflammatory disease, so one might expect the markers to be high. But this does not necessarily show in blood tests:

  • Kianpour, M., Nematbakhsh, M., & Ahmadi, S. M. (2012). C-reactive protein of serum and peritoneal fluid in endometriosis. Iranian journal of nursing and midwifery research, 17(2 Suppl1), S115. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696960/ 

“Findings: There was no significant difference between the CRP serum level in patients with endometriosis and infertile women without endometriosis. There was a significant difference in peritoneal level of CRP between case and control groups (p < 0.05). Conclusions: The findings suggested that measurement of this marker in patients’ serum or plasma cannot be used to diagnose endometriosis. It is further recommended that a combination of different markers might be helpful in this regard that could be studied in future.”

So we may not see an increase in the blood test, but there is a difference in the peritoneal (from the abdomen/pelvis) samples:

  • Kianpour, M., Nematbakhsh, M., & Ahmadi, S. M. (2012). C-reactive protein of serum and peritoneal fluid in endometriosis. Iranian journal of nursing and midwifery research, 17(2 Suppl1), S115. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696960/

“Compared to the control group, the CRP level of the peritoneal fluid were higher in patients with endometriosis (p<0.05). Pelvic endometriosis is a chronic inflammatory disease that is in association with a general inflammatory response in the peritoneal cavity.[34,35] This disease is known to have an immunological background.[36] Macrophage constitutes 82- 99% of the all the cell population of peritoneal fluid.[37–39] Literature has repeatedly reported an increase of total peritoneal fluid cell numbers, cell concentration and macrophages in endometriosis patients in compare to the control.[40–43] The study of Dunselman et al. also confirmed that there is an increase in the number and concentration of peritoneal cells in patients with endometriosis as compared to the control group.[38]” 

What is CA-125?

It’s a test that looks at markers for certain cancers, but if your doctor orders it and it’s high, don’t let it scare you. “…many noncancerous conditions can increase the CA 125 level. Many different conditions can cause an increase in CA 125, including normal conditions, such as menstruation, and noncancerous conditions, such as uterine fibroids” (Mayo Clinic, n.d.). 

Reference

Mayo Clinic. (n.d.). CA-125 test. Retrieved from http://www.mayoclinic.org/tests-procedures/ca-125-test/basics/definition/prc-20009524 

It can also be high in people with endometriosis: 

  • May, K. E., Conduit-Hulbert, S. A., Villar, J., Kirtley, S., Kennedy, S. H., & Becker, C. M. (2010). Peripheral biomarkers of endometriosis: a systematic review. Human reproduction update, 16(6), 651-674. Retrieved from http://humupd.oxfordjournals.org/content/16/6/651.full

“Studies published since continue to demonstrate a correlation between raised CA125 levels and endometriosis (Abrao et al., 1999; Somigliana et al., 2004; Agic et al., 2008; Seeber et al., 2008), and some imply a correlation with stage of disease (Chen et al., 1998; Amaral et al., 2006; Martinez et al., 2007; Rosa e Silva et al., 2007). One study has indicated that CA125 may be more accurate at diagnosing women with later stages of disease (Maiorana et al., 2007).”  

For more on peripheral biomarkers of endometriosis see:

May, K. E., Conduit-Hulbert, S. A., Villar, J., Kirtley, S., Kennedy, S. H., & Becker, C. M. (2010). Peripheral biomarkers of endometriosis: a systematic review. Human reproduction update, 16(6), 651-674. Retrieved from http://humupd.oxfordjournals.org/content/16/6/651.full 

3 years ago Symptoms No comment

Inflammation with endometriosis

Endometriosis is an inflammatory disorder. Inflammation involves a variety of inflammatory factors, such as cytokines, prostaglandins, macrophages, and tumor necrosis factor. Inflammation is influenced by hormones; however, hormone receptors are altered in endometriosis lesions, thus changing the way endometriosis responds to hormones. Inflammation can lead to increased pain, fatigue, and general feelings of unwellness. Sometimes this inflammation can be seen in blood tests, but not always. 

Inflammatory Mediators: 

 “It has long been acknowledged by both researchers and clinicians that endometriosis is a disease associated with inflammation and elevated cytokine levels 2,3. Altered cytokine production by both cells of the immune system and the endometriotic lesion tissue has been proposed (discussed below for each of the specified cytokines) to contribute to these elevated cytokine levels. One of the driving factors for the enhanced production of endometriotic lesion cytokines is an altered progesterone responsiveness associated with the disease. Progesterone exhibits anti-inflammatory actions, and as such, progesterone analogs have been used to treat endometriosis and its associated symptoms 4. Progestin (progesterone) treatment appears to be successful in most 5, but not all 6, women, and not all progestin formulations are effective in reducing endometriosis-associated pain 7. This inconsistency could be due to the progesterone resistance typical of endometriosis which may stem from altered progesterone receptor expression 8.”

  • Monsanto, S. P., Edwards, A. K., Zhou, J., Nagarkatti, P., Nagarkatti, M., Young, S. L., … & Tayade, C. (2016). Surgical removal of endometriotic lesions alters local and systemic proinflammatory cytokines in endometriosis patients. Fertility and sterility, 105(4), 968-977. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/26698677 

“Endometriotic lesion removal significantly alters the inflammatory profile both locally and systemically in women with endometriosis. Our findings indicate that ectopic lesions are the major drivers of systemic inflammation in endometriosis.”  

Mast Cells:

Mast cells are immune system cells that can stimulate inflammation (Graziottin, Skaper, & Fusco, 2014). Endometriosis is an inflammatory disease, and degranulating mast cells have been found in higher quantities in endometriosis lesions versus normal tissue (Hart, 2015; Indraccolo & Barbieri, 2010). Estrogen seems to stimulate mast cells to support the inflammatory process (Zhu et al., 2018). In fact, one study reported estrogen receptors are expressed on mast cells (although the action of estrogen on the mast cell is not described) (Hart, 2015). While many therapies for endometriosis involve lowering estrogen production by the feedback loop between the brain and the ovaries, it should be remembered that endometriosis lesions demonstrate production of estrogen themselves (and also show resistance to progesterone) (Delvoux et al., 2009). The inflammation created can lead to pain (Indraccolo & Barbieri, 2010).

*When looking at studies, it is important to keep in mind the aim of the study. Many are looking for novel drug development or therapies. However, they can still shed light on how endometriosis behaves and why it produces the symptoms and effects it does.

  • Indraccolo, U., & Barbieri, F. (2010). Effect of palmitoylethanolamide–polydatin combination on chronic pelvic pain associated with endometriosis: Preliminary observations. European Journal of Obstetrics & Gynecology and Reproductive Biology, 150(1), 76-79. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/S0301211510000424

“Inflammation can be considered one of the major causes of pain in endometriosis. In particular, degranulating mast cells have been found in significantly greater quantities in endometriotic lesions than in unaffected tissues. The increase in activated and degranulating mast cells is closely associated with nerve structures in painful endometriotic lesions. These observations indicate that inflammation due to mast cells may contribute to the development of pain and hyperalgesia in endometriosis.”

“A second disease/condition that also appears to involve neuroinflammation with mast cell involvement is endometriosis (EMS). EMS is clearly an estrogen-dependent chronic inflammatory disorder….Interestingly, peritoneal fluid from patients with EMS contains higher levels of some cytokines than those without this condition (e.g., MCP-1 and IL-8 [96])…. Mast cells are prominent in EMS tissue but whether their role(s) in EMS development and progression are central to the disease or peripheral with mast cells being drawn to the site of lesions is still being debated (discussed in [109])….Degranulated mast cells have been detected in EMS lesions [111] and activated mast cells implicated in the associated fibrosis [112]. Furthermore, mast cells have been reported to express estrogen receptors and thus should be responsive to the sex hormones [113]. In fact, estrogen has been reported to result in mast cell activation with release of mediators, in part due to interactions with ER-alpha [113]. Furthermore, mast cells in EMS lesions are commonly found in close approximation to neural elements in such lesions (discussed in [109, 114]). Such close approximation of these two elements in lesions is somewhat supportive of the concept of active neuroinflammation and pain in EMS [115] and is analogous to what we have observed in abnormal skin wound healing and joint contraction models previously that were responsive to mast cell stabilizer interventions [13, 16, 17].”

“Mast cells are immune cells now viewed as cellular sensors in inflammation and immunity. When stimulated, mast cells release an array of mediators to orchestrate an inflammatory response. These mediators can directly initiate tissue responses on resident cells, and may also regulate the activity of other immune cells, including central microglia. New evidence supports the involvement of peripheral and central mast cells in the development of pain processes as well as in the transition from acute, to chronic and neuropathic pain. That behavioral and endocrine states can increase the number and activation of peripheral and brain mast cells suggests that mast cells represent the immune cells that peripherally and centrally coordinate inflammatory processes in neuropsychiatric diseases such as depression and anxiety which are associated with chronic pelvic pain. Given that increasing evidence supports the activated mast cell as a director of common inflammatory pathways/mechanisms contributing to chronic and neuropathic pelvic pain and comorbid neuropsychiatric diseases, mast cells may be considered a viable target for the multifactorial management of both pain and depression.”

Chronic Inflammation causes unwell feeling and depression: This inflammation often gives rise to a general unwell feeling:

  • Elenkov, I. J., Iezzoni, D. G., Daly, A., Harris, A. G., & Chrousos, G. P. (2005). Cytokine dysregulation, inflammation and well-being. Neuroimmunomodulation, 12(5), 255-269. Retrieved from https://pubmed.ncbi.nlm.nih.gov/16166805/ 

“Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis , health, and well-being. Like the stress response, the inflammatory reaction is crucial for survival and is meant to be tailored to the stimulus and time. A full-fledged systemic inflammatory reaction results in stimulation of four major programs: the acute phase reaction, the sickness syndrome, the pain program, and the stress response, mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Common human diseases such as atopy/allergy, autoimmunity, chronic infections and sepsis are characterized by a dysregulation of the pro- versus anti-inflammatory and T helper (Th)1versus Th2 cytokine balance. Recent evidence also indicates the involvement of pro-inflammatory cytokines in the pathogenesis of atherosclerosis and major depression, and conditions such as visceral-type obesity, metabolic syndrome and sleep disturbances. During inflammation, the activation of the stress system, through induction of a Th2 shift, protects the organism from systemic ‘overshooting’ with Th1/pro-inflammatory cytokines. Under certain conditions, however, stress hormones may actually facilitate inflammation through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor- and C-reactive protein production and through activation of the corticotropin releasing hormone/substance P-histamine axis. Thus, a dysfunctional neuroendocrine-immune interface associate with abnormalities of the systemic anti-inflammatory feedback’ and/or ‘hyperactivity’ of the local pro-inflammatory factors may play a role in the pathogenesis of atopic/allergic and autoimmune diseases, obesity, depression, and atherosclerosis. These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health. These hypotheses require further investigation, but the answers should provide critical insights into mechanisms underlying a variety of common human immune-related diseases.”  

  • Dantzer, R., O’Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008). From inflammation to sickness and depression: when the immune system subjugates the brain. Nature reviews neuroscience, 9(1), 46-56. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919277/ 

“Anyone who has experienced a viral or bacterial infection knows what it means to feel sick. The behaviour of sick people changes dramatically; they often feel feverish and nauseated, ignore food and beverages, and lose interest in their physical and social environments. They tire easily and their sleep is often fragmented. In addition, they feel depressed and irritable, and can experience mild cognitive disorders ranging from impaired attention to difficulties in remembering recent events. Despite their negative impact on well-being, these symptoms of sickness are usually ignored. They are viewed as uncomfortable but banal components of infections1. Sickness is a normal response to infection, just as fear is normal in the face of a predator. It is characterized by endocrine, autonomic and behavioural changes and is triggered by soluble mediators that are produced at the site of infection by activated accessory immune cells. These mediators are known as pro-inflammatory cytokines, and include interleukin-1α and β (IL-1α and IL-1β), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6). They coordinate the local and systemic inflammatory response to microbial pathogens. However, these peripherally produced cytokines also act on the brain to cause the aforementioned behavioural symptoms of sickness. Recently, it has been suggested that ‘sickness behaviour’2,3, a term used to describe the drastic changes in subjective experience and behaviour that occur in physically ill patients and animals, is an expression of a previously unrecognized motivational state. It is responsible for re-organizing perceptions and actions to enable ill individuals to cope better with an infection4. During the last five years, it has been established that pro-inflammatory cytokines induce not only symptoms of sickness, but also true major depressive disorders in physically ill patients with no previous history of mental disorders. Some of the mechanisms that might be responsible for inflammation-mediated sickness and depression have now been elucidated. These findings suggest that the brain–cytokine system, which is in essence a diffuse system, is the unsuspected conductor of the ensemble of neuronal circuits and neurotransmitters that organize physiological and pathological behavior….” 

References

Delvoux, B., Groothuis, P., D’Hooghe, T., Kyama, C., Dunselman, G., & Romano, A. (2009). Increased production of 17β-estradiol in endometriosis lesions is the result of impaired metabolism. The Journal of Clinical Endocrinology & Metabolism, 94(3), 876-883. Retrieved from https://academic.oup.com/jcem/article/94/3/876/2596530

Graziottin, A., Skaper, S. D., & Fusco, M. (2014). Mast cells in chronic inflammation, pelvic pain and depression in women. Gynecological Endocrinology, 30(7), 472-477. Retrieved from https://www.tandfonline.com/doi/abs/10.3109/09513590.2014.911280

Hart, D. A. (2015). Curbing inflammation in multiple sclerosis and endometriosis: should mast cells be targeted?. International journal of inflammation, 2015. Retrieved from https://www.hindawi.com/journals/iji/2015/452095/

Indraccolo, U., & Barbieri, F. (2010). Effect of palmitoylethanolamide–polydatin combination on chronic pelvic pain associated with endometriosis: Preliminary observations. European Journal of Obstetrics & Gynecology and Reproductive Biology, 150(1), 76-79. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/S0301211510000424

Zhu, T. H., Ding, S. J., Li, T. T., Zhu, L. B., Huang, X. F., & Zhang, X. M. (2018). Estrogen is an important mediator of mast cell activation in ovarian endometriomas. Reproduction, 155(1), 73-83. Retrieved from https://rep.bioscientifica.com/view/journals/rep/155/1/REP-17-0457.xml

3 years ago Symptoms No comment

Bowel/GI endometriosis

Gastrointestinal (GI) symptoms are common with endometriosis, anywhere from one third to up to 85% of endometriosis patients have GI symptoms, usually with a gradual onset (Aragon & Lessey, 2017; Ek et al., 2015). Of those with GI symptoms, the location of endometriosis lesions weren’t necessarily on the bowel itself (Ek et al., 2015).  Women with endometriosis are often diagnosed with irritable bowel syndrome (IBS); but one study noted that when those individuals have surgery for endometriosis, the individuals had endometriosis lesions on or near the rectum or in the pouch of Douglas (posterior cul-de-sac) and had generally minimal or mild disease (Aragon & Lessey, 2017). The symptoms are attributed to the inflammatory process from endometriosis (Aragon & Lessey, 2017)

The incidence of endometriosis on the bowel itself ranges from 5% to 12% of those with endometriosis, most often seen on the rectum and sigmoid colon  (Habib et al., 2020). Those with lesions on or close to the bowel did have more nausea and vomiting (Ek et al., 2015). Other reported symptoms include “a myriad of symptoms such as alteration in bowel habits (constipation/diarrhoea), dyschezia, dysmenorrhoea and dyspareunia in addition to infertility” (Habib et al., 2020, para. 1). Bowel endometriosis is associated with lesions on the uterosacral ligaments  and vaginal wall, which can cause painful penetration (Habib et al., 2020). Treatments for endometriosis that actually worsened GI symptoms included opioids and GnRH analogs (Ek et al., 2015). 

While hormonal medications have been shown to help relieve symptoms, it may not stop the progression of the disease which can lead, in severe cases, to bowel obstruction; therefore, it is recommended that close follow-up be utilized if you do not choose surgical treatment (Habib et al., 2020; Ferrero et al., 2011). If you think you might have bowel involvement, it is important to find the right care. The success of surgery depends on the skills and experience of the surgeon and a multidisciplinary team. It is recommended that “surgery should be performed by experienced surgeons, in centres with access to multidisciplinary care” (Habib et al., 2020, para. 1). Before committing to surgery, you want to know how they remove endometriosis; how often do they perform this surgery; does the surgeon have the advanced knowledge/surgical skills to address all disease in all locations (bowel, bladder, near ureters, culs de sac, uterine ligaments, etc.). Learning what questions to ask and choosing the right surgeon can make all the difference.

When working up symptoms of the bowel, many doctors may suggest a colonoscopy, which can rule out other problems such as colitis, polyps, diverticulosis or diverticulitis. However, in one study, a colonoscopy did not diagnose intestinal endometriosis in 92% of the patients and the authors conclude that a colonoscopy “should not be routinely performed in the diagnostic work-up of bowel endometriosis” (Milone et al., 2015, para. 4). Bowel endometriosis is treatable, without full laparotomy and without colostomy (Tarjanne, Heikinheimo, Mentula, & Härkki, 2015).

*Dyschezia- excessive straining with stools, dysmenorrhoea- pain with menstruation, dyspareunia- painful intercourse

Gastrointestinal (GI) Disease: 

Links:

Studies:

  • Rectosigmoid Endometriosis Surgery: Moawad, N. S., Guido, R., Ramanathan, R., Mansuria, S., & Lee, T. (2011). Comparison of laparoscopic anterior discoid resection and laparoscopic low anterior resection of deep infiltrating rectosigmoid endometriosis. JSLS: Journal of the Society of Laparoendoscopic Surgeons, 15(3), 331. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183552/

“…patients often present with severe symptoms, such as dyschezia, dysmenorrhea, dyspareunia, and chronic pelvic pain, along with a spectrum of bowel symptoms like diarrhea, constipation, bloating, or cyclic rectal bleeding. The triad of dysmenorrhea, dyspareunia, and bowel symptoms was found to be 80% sensitive for diagnosing bowel endometriosis.1,6–8 Multifocal bowel involvement is common, affecting 25% to 34% of patients.2,9

“Although medical and hormonal therapy have been found to be effective for improving the pain symptoms associated with rectal endometriosis, the relief is usually transient and symptoms generally recur once medical therapy is discontinued.10 Due to persistent or recurrent pain, and the marked anatomic distortion caused by deep infiltrating rectovaginal endometriosis, surgery is considered the treatment of choice for symptomatic disease.11 Moreover, surgery is mandatory in severe cases of rectovaginal nodules that result in luminal stenosis and obstructive symptoms.12

“Multiple studies suggest that complete excision of endometriotic lesions, including bowel resection when necessary, results in significant improvement in pain, as well as improvement in bowel symptoms and quality of life.9,13–15.”

“Bowel endometriosis affects between 3.8% and 37% of women with endometriosis. The evaluation of symptoms and clinical examination are inadequate for an accurate diagnosis of intestinal endometriosis. Transvaginal ultrasonography is the first line investigation in patients with suspected bowel endometriosis and allows accurate determination of the presence of the disease. Radiological techniques (such as magnetic resonance imaging and multidetector computerized tomography enteroclysis) are useful for estimating the extent of bowel endometriosis. Hormonal therapies (progestins, gonadotropin releasing hormone analogues and aromatase inhibitors) significantly improve pain and intestinal symptoms in patients with bowel stenosis less than 60% and who do not wish to conceive. However, hormonal therapies may not prevent the progression of bowel endometriosis and, therefore, patients receiving long-term treatment should be periodically monitored. Surgical excision of bowel endometriosis should be offered to symptomatic patients with bowel stenosis greater than 60%. Intestinal endometriotic nodules may be excised by nodulectomy or segmental resection. Both surgical procedures improve pain, intestinal symptoms and fertility. Nodulectomy may be associated with a lower rate of complications.”

  • Bowel Endometriosis Surgery Study: Afors, K., Centini, G., Fernandes, R., Murtada, R., Zupi, E., Akladios, C., & Wattiez, A. (2016). Segmental and discoid resection are preferential to bowel shaving for medium-term symptomatic relief in patients with bowel endometriosis. Journal of Minimally Invasive Gynecology, 23(7), 1123-1129. Retrieved from https://pubmed.ncbi.nlm.nih.gov/27544881/ 

“All 3 treatment modalities are effective in terms of immediate symptom relief with acceptable complication rates. However, significantly higher rates of symptom recurrence and reintervention were noted in the shaving group, whereas segmental resection is more likely to be indicated in cases of large nodules.”

  • Case Study of Endometriosis Causing A Small Bowel Obstruction: Slesser, A. A., Sultan, S., Kubba, F., & Sellu, D. P. (2010). Acute small bowel obstruction secondary to intestinal endometriosis, an elusive condition: a case report. World Journal of Emergency Surgery, 5(1), 27. Retrieved from https://wjes.biomedcentral.com/articles/10.1186/1749-7922-5-27 

“We present the case of a 33 year old female of Asian origin who presented with symptoms and signs of an acute small bowel obstruction. A right hemicolectomy for suspected malignancy was performed with an ileocolic anastomosis. Histological examination demonstrated extensive endometriosis of the appendix and ileocaecal junction. Conclusion: Enteric endometriosis should be considered as a differential diagnosis when assessing females of reproductive age with acute small bowel obstruction. A high index of suspicion is required to arrive at a diagnosis of this elusive condition.”

  • Extremely rare case of gastric endometriosis:

Ha, J. K., Choi, C. W., Kim, H. W., Kang, D. H., Park, S. B., Kim, S. J., & Hong, J. B. (2015). An extremely rare case of gastric subepithelial tumor: gastric endometriosis. Clinical endoscopy, 48(1), 74. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323438/ 

“Frequent locations for endometriosis outside of the pelvic cavity include a variety of tissues and organs, such as the intestines, kidneys, lungs, skin, and pleura, with the exception of the spleen.1 Endometriosis affects the gastrointestinal tract in 5% of cases, with the sigmoid colon being the most commonly affected location, followed by the rectum.2,3 However, to the best of our knowledge, the present case is among the very few reports of gastric endometriosis. Here, we report a very rare case of gastric endometriosis that presented as a subepithelial tumor.”

  • Hepatic (liver) endometriosis a rare case and literature review:

Liu, K., Zhang, W., Liu, S., Dong, B., & Liu, Y. (2015). Hepatic endometriosis: a rare case and review of the literature. European Journal of Medical Research, 20(1), 48. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4389341/

“…endometriotic lesions have also been described in almost all other remote organs of the human body, including the omentum, gastrointestinal tract, peritoneum, operative scars, lymph nodes, umbilicus, skin, lungs, pleura, bladder, kidneys, pancreas, and even in males [3]. Hepatic endometriosis, one of the rarest forms of atypical endometriosis, was first described in 1986 [4]. To our knowledge, only 21 cases of hepatic endometriosis have been previously reported in the literature. We herein describe the 22nd case of hepatic endometriosis and evaluate the current literature addressing the diagnosis of hepatic endometriosis focusing on advances in the clinical manifestation, pathogenesis, and diagnostic workup.”

Bloating with endometriosis:

  • Ek, M., Roth, B., Ekström, P., Valentin, L., Bengtsson, M., & Ohlsson, B. (2015). Gastrointestinal symptoms among endometriosis patients—A case-cohort study. BMC women’s health, 15(1), 59. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4535676/

“Conclusions: The majority of endometriosis patients experience more severe gastrointestinal symptoms than controls. A poor association between symptoms and lesion localization was found, indicating existing comorbidity between endometriosis and irritable bowel syndrome (IBS). Treatment with opioids or GnRH analogs is associated with aggravated gastrointestinal symptoms….Gastrointestinal symptoms among patients with endometriosis described in the literature include abdominal pain, bloating, nausea, constipation, vomiting, painful bowel movements, and diarrhea [3–5]. However, reported symptoms differ between studies. Aggravated symptoms during menstruation have been reported [4, 6, 7] such as cyclic-related bloating and constipation [4]. Fauconnier et al. [7] concluded that symptoms including diarrhea, constipation, and colic rectal pain were more frequent among patients with endometriosis lesions within or close to the bowel. In contrast, Maroun et al. [3] reported gastrointestinal symptoms to be primarily independent of localization of endometriosis lesions in relation to the bowel. Different explanations concerning the occurrence of these symptoms include: endometriosis lesions cause inflammatory activity and local prostaglandin release, which can alter bowel function [8]; endometriosis lesions within the bowel cause symptoms due to mechanical obstruction or cyclic micro-hemorrhages [9]; or there is an existing comorbidity between endometriosis and irritable bowel syndrome (IBS) [8].”

  • Luscombe, G. M., Markham, R., Judio, M., Grigoriu, A., & Fraser, I. S. (2009). Abdominal bloating: an under-recognized endometriosis symptom. Journal of Obstetrics and Gynaecology Canada, 31(12), 1159-1171. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/20085682 

“A significantly larger proportion of women with endometriosis than control subjects experienced abdominal bloating (96% vs. 64%). In women with abdominal bloating, the following were more common in those who had endometriosis: associated severe discomfort (30% vs. 0%), wearing loose clothes during bloating (87% vs. 38%), and simultaneous hand swelling (30% vs. 6%). The experiences of cyclically related diarrhea and constipation were more frequent with endometriosis. While there were significant changes in bloating and discomfort ratings across the menstrual cycle, there was a trend towards a difference between the control subjects and unmedicated endometriosis groups only in how the pattern of bloating severity fluctuated across the cycle. Lower abdominal girth measurements changed significantly across menstrual cycle phases. Control and unmedicated endometriosis groups differed significantly in girth changes across the menstrual cycle, controls experiencing much less variation. Compared with the unmedicated endometriosis group, women receiving hormonal treatment had higher bloating severity ratings and discomfort scores, but there was no objective difference in abdominal girth. Conclusion: Painful abdominal bloating appears to be common in women with endometriosis and causes considerable symptomatic distress.”

“Colorectal surgery for endometriosis has a significant impact on urinary function regardless of the technique. However, rectal shaving causes less postoperative voiding dysfunction than discoid excision or segmental resection.”

As pelvic floor dysfunction and other issues can contribute to bowel symptoms.

References

Aragon, M., & Lessey, B. A. (2017). Irritable Bowel Syndrome and Endometriosis: Twins in Disguise. GHS Proc, 43-50. Retrieved from https://hsc.ghs.org/wp-content/uploads/2016/11/GHS-Proc-Ibs-And-Endometriosis.pdf

Ek, M., Roth, B., Ekström, P., Valentin, L., Bengtsson, M., & Ohlsson, B. (2015). Gastrointestinal symptoms among endometriosis patients—A case-cohort study. BMC women’s health, 15(1), 59. doi: 10.1186/s12905-015-0213-2

Ferrero, S., Camerini, G., Maggiore, U. L. R., Venturini, P. L., Biscaldi, E., & Remorgida, V. (2011). Bowel endometriosis: Recent insights and unsolved problems. World journal of gastrointestinal surgery, 3(3), 31. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069336/

Habib, N., Centini, G., Lazzeri, L., Amoruso, N., El Khoury, L., Zupi, E., & Afors, K. (2020). Bowel Endometriosis: Current Perspectives on Diagnosis and Treatment. International Journal of Women’s Health, 12, 35. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996110/

Milone, M., Mollo, A., Musella, M., Maietta, P., Fernandez, L. M. S., Shatalova, O., … & Milone, F. (2015). Role of colonoscopy in the diagnostic work-up of bowel endometriosis. World Journal of Gastroenterology: WJG, 21(16), 4997. doi: 10.3748/wjg.v21.i16.4997

Tarjanne, S., Heikinheimo, O., Mentula, M., & Härkki, P. (2015). Complications and long‐term follow‐up on colorectal resections in the treatment of deep infiltrating endometriosis extending to bowel wall. Acta Obstetricia et Gynecologica Scandinavica, 94(1), 72-79. Retrieved from https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/aogs.12515

3 years ago Symptoms No comment

Post coital bleeding

Post coital bleeding (bleeding after sex) is common and usually benign, but it does requires thorough history and exam and perhaps additional testing. Some of the common reasons for bleeding after sex can include:

  • “cervical polyps
  • endometrial polyps
  • endometriosis
  • uterine leiomyomata
  • Cervicitis or cervical lesions
  • pregnancy
  • vaginitis
  • endometrial cancer
  • coagulopathy” (Smith, 2008)

Studies:

“Postcoital bleeding can be an annoying complaint for patients and a worrisome symptom for providers due to the risk of underlying malignancy. Despite being a common gynecologic problem, there is large diversity among gynecologists on the management of postcoital bleeding [55]. Unlike abnormal uterine bleeding or the management of abnormal cytology, there are no recommendations from governing bodies on the management of postcoital bleeding. Patients presenting with postcoital bleeding require a full history and physical examination to help in developing a differential diagnosis to guide evaluation and treatment. Although most patients with postcoital bleeding do not have underlying malignancy, providers must pay close attetion to ensure that appropriate screening tests are up-to-date. Physicians should also be aware that a large portion of women presenting with postcoital bleeding will not have an obvious source for their bleeding; however, as long as malignancy is ruled out, most of these women’s symptoms will naturally resolve in premenopausal women.?” 

Reference

  • Smith, R. (2008). Netters Obsetrics & Gynecology ( 2nd ed.). Elsevier: Philadelphia, PA.
3 years ago Symptoms No comment

Sexual functioning Pain with Penetration

Pain with any type of penetration, such as from a tampon or from a physical exam, is a symptom of endometriosis. Pain may often be felt with sexual activity. Pain can be from pulling or stretching of tissue. It can also be from pelvic floor dysfunction or other problems with the muscles and ligaments of the pelvic floor. Physical therapy can be useful for this symptom. 

“Dyspareunia is the medical term for pain during sex. It frequently occurs in people with endometriosis because penetration and other movements associated with intercourse can stretch and pull the endometrial growths…. Penetration and other movements related to intercourse can pull and stretch endometrial tissue, particularly if it has grown behind the vagina or lower uterus. Vaginal dryness can also cause this pain. Some means of addressing endometriosis, such as hormonal treatments or a hysterectomy (surgical removal of the uterus), can cause dryness…. Those who do may experience the following:

  • pain that is acute or feels like stabbing
  • pain deep in the abdomen
  • pain ranging from mild to severe

“This pain varies from person to person and may depend on the type of intercourse. Some experience pain only during deep penetration, for example, while others experience pain after sex, rather than during it.” 

Links:

Studies:

  • Melis, I., Litta, P., Nappi, L., Agus, M., Melis, G. B., & Angioni, S. (2015). Sexual function in women with deep endometriosis: correlation with quality of life, intensity of pain, depression, anxiety, and body image. International Journal of Sexual Health, 27(2), 175-185. Retrieved from https://www.tandfonline.com/doi/full/10.1080/19317611.2014.952394 

“The study evidenced that deep endometriosis has a significant impact on sexuality and body image.”

  • Williams, C., Hoang, L., Yosef, A., Alotaibi, F., Allaire, C., Brotto, L., … & Yong, P. J. (2016). Nerve bundles and deep dyspareunia in endometriosis. Reproductive Sciences, 23(7), 892-901. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/26711313

“This study provides evidence that neurogenesis in the cul-de-sac/uterosacrals may be an etiological factor for deep dyspareunia in endometriosis.”

3 years ago Symptoms No comment

Nerves and endometriosis

“Endometriosis lesions are known to be hyperinnervated” (Liu, Yan, & Guo, 2019). People with endometriosis have abnormal nerve growth and nerve fibers close to endometriosis lesions (Zheng, Zhang, Leng, & Lang, 2019). Pain with endometriosis is multifactorial, including irritation of nerves in the pelvis, new nerve growth, heightened sensitivity to pain, inflammation in the pelvis, and pain producing agents in the pelvic fluid (Ferrero, Vellone, & Barra, 2019).  The interplay between nerves and inflammation is believed to play a significant role in pain. There are increased levels of multiple inflammatory factors in and around endometriosis lesions (Wei et al., 2020). Endometriosis “can also directly irritate and infiltrate pelvic nerves promoting endometriosis-associated pain” (Ferrero, Vellone, & Barra, 2019) and can lead “to corresponding neurological symptoms or deficits” (Working group of ESGE et al., 2020).

Studies:

“Endometriotic lesions are known to be hyperinnervated due to neurogenesis resulting from neutrophins secreted by endometriotic lesions and possibly platelets. These neutrophins seem to preferentially favour production of sensory neurons at the expense of sympathetic neurons….Since sensory nerves are known to be important in wound healing and fibrogenesis, our findings also give more credence to the notion that endometriotic lesions are wounds undergoing repeated tissue injury and repair.”

“…endometriosis is certainly a chronic inflammation disorder [4]. The levels and concentrations of active macrophages; interleukin (IL)-1β, IL-6, IL-8; nerve growth factor (NGF); other immune cells; and inflammatory factors are increased in peritoneal fluid (PF) and endometriotic lesions [4,5,6]. These changes are believed to contribute to serious symptoms of pain such as chronic pelvic pain, dysmenorrhea, and dyspareunia [7]. Notably in deep infiltrating endometriosis (DIE) and intestinal endometriosis, the anatomical distribution of lesions is normally more closely related to pelvic pain symptoms [2]. Abnormal innervations are observed in most endometriotic lesions: an increased number of total intact nerve fibers, increased sensory and decreased sympathetic nerve fiber density (NFD) [6], the occurrence of cholinergic and unmyelinated nerve fibers, etc. [8] In various studies, these abnormal phenomena have been correlated with endometriosis-associated pain [6, 8,9,10]. More importantly, sympathetic and parasympathetic systems have different inflammation-related effects in different stages of inflammation [10].”

“A growing body of evidence attests that patients with endometriosis endure pain associated with abnormal angiogenesis and the growth of novel nerve fibers in close proximity to ectopic lesions. Endometriotic lesions create an inflammatory environment and change the quality or quantity of inflammatory mediators or neurotransmitters, thereby stimulating peripheral nerve sensitization by remodeling the structure of peripheral synapses and accelerating conduction along nerve fibers…. Endometriosis-related pain is currently considered a form of neuropathic or neuroinflammatory pain.”

“The pathophysiology of the association between pain and endometriosis is still enigmatic. The cause of pain is likely to be multifactorial (Table 1) (9,10). In patients with severe endometriosis with large ovarian cysts and DIE, pain can be caused by the distortion of the pelvic anatomy and by the presence of extensive adhesions (involving the uterus, the ovaries and the rectosigmoid) (Figure 1) (10). However, there is a poor correlation between the degree of pain and the severity of endometriosis. Some patients with intense pain symptoms have only small endometriotic implants on the peritoneal surface while other patients with severe endometriosis are almost asymptomatic….patients with endometriosis have an inflammatory process within the peritoneal cavity. In fact, women with endometriosis have increased concentration of inflammatory cells (macrophages and T lymphocytes), chemokines (MCP1, RANTES), inflammatory cytokines (IL1β, IL6, IL8, TNFα) and inflammatory molecules in the peritoneal fluid (11). These molecules and cells can sensitize peripheral nerves promoting the generation of pain (12). In addition, some pain-inducing molecules (such as prostaglandins) have elevated concentration in peritoneal fluid of women with endometriosis. Finally, endometriotic nodule can also directly irritate and infiltrate pelvic nerves promoting endometriosis-associated pain (13).”

  • Working group of ESGE, ESHRE, and WES, Keckstein, J., Becker, C. M., Canis, M., Feki, A., Grimbizis, G. F., … & Tanos, V. (2020). Recommendations for the surgical treatment of endometriosis. Part 2: deep endometriosis. Human Reproduction Open, 2020(1), hoaa002. Retrieved from https://academic.oup.com/hropen/article/2020/1/hoaa002/5733057

“Endometriosis close to the sympathetic and parasympathetic nerve fibres (hypogastric plexus and splanchnic nerves) can lead to a dysfunction of pelvic organs (e.g. dysfunction of the bladder as well as disturbance of vaginal lubrication and intestinal dysfunction) (Possover, 2014). Involvement of somatic nerves, such as the sacral plexus and the sciatic nerve, leads to corresponding neurological symptoms or deficits.”

References

Ferrero, S., Vellone, V. G., & Barra, F. (2019). Pathophysiology of pain in patients with peritoneal endometriosis. Annals of translational medicine, 7(Suppl 1). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462618/

Liu, X., Yan, D., & Guo, S. W. (2019). Sensory nerve-derived neuropeptides accelerate the development and fibrogenesis of endometriosis. Human Reproduction, 34(3), 452-468. Retrieved from https://academic.oup.com/humrep/article-abstract/34/3/452/5303712

Wei, Y., Liang, Y., Lin, H., Dai, Y., & Yao, S. (2020). Autonomic nervous system and inflammation interaction in endometriosis-associated pain. Journal of Neuroinflammation, 17(1), 1-24. Retrieved from https://link.springer.com/article/10.1186/s12974-020-01752-1

Working group of ESGE, ESHRE, and WES, Keckstein, J., Becker, C. M., Canis, M., Feki, A., Grimbizis, G. F., … & Tanos, V. (2020). Recommendations for the surgical treatment of endometriosis. Part 2: deep endometriosis. Human Reproduction Open, 2020(1), hoaa002. Retrieved from https://academic.oup.com/hropen/article/2020/1/hoaa002/5733057

Zheng, P., Zhang, W., Leng, J., & Lang, J. (2019). Research on central sensitization of endometriosis-associated pain: a systematic review of the literature. Journal of pain research, 12, 1447. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514255/

3 years ago Symptoms No comment

Sciatic Pain and Endometriosis

While endometriosis may not necessarily have to be on the sciatic nerve to cause similar symptoms, there have been some cases documented of that happening. Some symptoms could be: cyclical pain along the sciatic nerve (sciatica), back pain, gluteal pain radiating to the front of the thigh and outside the lower leg, positive straight leg raise test (seen in low back disc injuries as well), sensory loss, changes in reflexes, and muscle weakness (Foti et al., 2018). There are multiple case studies demonstrating endometriosis affecting the sciatic nerve region. However, symptoms can occur from lesions near that region (like the side posterior pelvic area) (Vilos, Vilos, & Haebe, 2002). Pelvic floor dysfunction and other myofascial disorders (such as piriformis syndrome) can also cause similar symptoms (Cass, 2015; Weiss, Rich, & Swisher, 2012). As is often seen with endometriosis, there may be more than one pain/symptom generator present. This might mean utilizing different providers, such as a pelvic physical therapist as well as a surgeon, in order to address all the underlying issues.

Read more about Endometriosis symptoms and Types of Endometriosis Pain (endometriosis back pain & endometriosis Leg Pain )

Studies:

“Cyclic leg signs and symptoms were associated with pelvic peritoneal pockets, endometriosis nodules, or surface endometriosis of the posterolateral pelvic peritoneum. We hypothesize that the pain associated with these lesions is more likely referred pain originating from pelvic peritoneum than direct irritation of the lumbosacral plexus of the sciatic nerve.” “Endometriosis is a common gynecological disorder that can cause musculoskeletal symptoms and manifest as nonspecific low back pain. The patient was a 25-year-old woman who reported the sudden onset of severe left-sided lumbosacral, lower quadrant, buttock, and thigh pain. The physical therapist examination revealed findings suggestive of a pelvic visceral disorder during the diagnostic process. The physical therapist referred the patient for medical consultation, and she was later diagnosed by a gynecologist with endometriosis and a left ovarian cyst.” “Radiating leg pain related to the menstrual cycle has been reported as a complication of endometriosis in a number of case studies (Baker et al., 1966; Bjornsson, 1976; Denton & Sherrill, 1955; Floyd et al., 2011; Forrest & Brooks, 1972; Head et al., 1962; Motamedi et al., 2015; Pacchiarotti et al., 2013), and in two surveys (Missmer & Bove, 2011; Walch et al., 2014). A consistent and thus perhaps key diagnostic feature seems to be the cyclical or catamenial nature of the symptom, especially earlier in the progression of the endometriosis (Capek et al., 2016; Dhote et al., 1996; Moeser et al., 1990; Takata & Takahashi, 1994; Zager et al., 1998). However, the symptom duration usually expands with endometriosis progression, developing into constant pain if left untreated. “Examination findings in women with leg pain due to endometriosis are typical of sciatica due to other causes (Torkelson et al., 1988), including painful straight leg raising testing, and may also include a diminished Achilles tendon reflex, mild muscular atrophy, and tenderness of the sciatic nerve at the sciatic notch. Lumbar spinal investigations (myelogram, CSF analysis) are usually unremarkable, but magnetic resonance imaging can demonstrate larger lesions (Binkovitz et al., 1991; Cottier et al., 1995; Yekeler et al., 2004). “Surgical descriptions of sciatic endometriosis describe inflammatory lesions that involve surrounding structures that are not necessarily otherwise diseased (Descamps et al., 1995; Yekeler et al., 2004). In an animal model, it has been shown that a focal inflammation of the sciatic nerve (called sciatic neuritis) evokes mechanical sensitivity in the axons of a subset of nociceptive (potentially pain-evoking) neurons without causing overt nerve damage (Bove et al., 2003; Dilley & Bove, 2008; Dilley et al., 2005). Furthermore, the sheaths of nerve trunks are innervated by mechanically and chemically-sensitive nociceptors (Bove & Light, 1995a, b, 1997), which also participate in maintaining the local environment of the nerve (Sauer et al., 1999). These findings suggest that inflamed nerves are a source of pain perceived as coming from the nerve and as coming from the structure(s) that the nerve innervates.” “Endometriosis (EN) is a common gynecological condition characterized by the presence of functional endometrium located outside the uterine cavity. Sciatic nerve (SN) is rarely affected by EN. Magnetic resonance imaging allows a direct visualization of the spinal and SN, and it is the modality of choice for the study of SN involvement in extrapelvic EN. We report a case of an endometrioma located in the right SN with a systematic review of the literature.” “The patient is a 49-year-old perimenopausal woman with dysmenorrhea and a left ovarian cyst who presented for evaluation of new onset left hip and leg pain. The left ovarian cyst was first noted 4 years ago and the patient declined surgery at that time, instead opting for surveillance with repeat imaging which now demonstrated an interval increase in the cyst size. The patient had an extensive evaluation for her leg pain including MRI and nerve conduction studies which were all unremarkable. The patient declined medical management or definitive surgical treatment of the suspected endometriosis. She opted for a diagnostic laparoscopy and left ovarian cystectomy.” “A 35-year-old female patient consulted for right low back pain extending along her posterior thigh, calf and foot since 2 years. The pain was recurrent, acute in onset, lasted several days and gradually diminished until disappearing. It was refractory to common analgesics and during the crisis she had difficulties to walk. Neurologist requested a calendar of pain in which the relationship between the menstrual cycle and the pain became evidenced. We performed MRN of the lumbo sacral plexus that showed multiple endometriotic implants in ovaries, L5-S1 roots and a huge one on the sciatic nerve (intra and extrapelvic segment). The patient started oral contraceptives but presented progressive worsening of pain until it became constant and developed step page. Electromyogram showed acute and chronic axonal damage in the sciatic nerve distribution. Medical treatment was changed to leuprolide acetate. The patient evolved with improvement of ovarian endometriosis but persistence of sciatic nerve lesions, leg pain and weakness up to now. Surgical option was considered.” “A 25-year-old woman presented to her general practitioner with a two-month history of constant pain in her thigh. There was no history of trauma and the onset was insidious. A diagnosis of a soft-tissue injury was made. However, despite anti-inflammatory medication and physiotherapy she developed increasing pain, typically sciatic in nature, from the left buttock, radiating down the posterolateral aspect of the leg and heel. This would escalate to a severe left-sided sciatic pain during menstruation. Two years later she had developed a limp and was referred to an orthopaedic surgeon. At the time of clinical assessment she had marked pain (Visual Analogue Scale (VAS)2 7 and Peripheral Nerve Injury (PNI) scale3 2) and required either two crutches or a wheelchair. On examination, she had an antalgic gait and was unable to bear weight fully on her left leg because of the pain in her buttock and leg. The pain was exacerbated by hip flexion and knee extension. There was no apparent muscle wasting or sympathetic changes in the leg and foot. Palpation of the left gluteal region, especially over the sciatic notch, was painful. Motor power was preserved throughout the leg, except for some weakness in the biceps femoris. Straight-leg raising was to 30° only. Reflexes were present, but the ankle jerk only with reinforcement. Sensation to pin-prick, temperature and light touch was reduced in the heel and sole of the foot. “The diagnosis of sciatic endometriosis was considered…Histopathological examination confirmed endometriosis of the sciatic nerve with no evidence of malignancy (Figs 4 and 5). Post-operatively and at 12 months follow-up her pain was considerably relieved (VAS2 2, PNI3 1). She was able to walk without crutches and could straighten the leg. There was an improvement in sensation over the heel and sole of the foot to pin-prick, temperature and light touch. She was referred to a gynaecologist, who performed a laparoscopy which now showed no evidence of intra-pelvic endometriosis.” “A 20-year-old woman presented with complaints of severe dysmenorrhea lasting for more than 6 years and dysfunction of her left lower limb lasting for approximately 4 months. Both CT and MRI demonstrated a suspected intrapelvic and extrapelvic endometriotic cyst (7.3 cm × 8.1 cm × 6.5 cm) passing through the left greater sciatic foramen. Laparoscopic exploration showed a cyst full of dark fluid occupying the left obturator fossa and extending outside the pelvis. A novel combination of transgluteal laparoscopy was performed for complete resection of the cyst and decompression of the sciatic nerve. Postoperative pathology confirmed the diagnosis of endometriosis. Long-term follow-up observation showed persistent pain relief and lower limb function recovery in the patient.” “We report a case of a 32-year-old patient who presented with cyclic leg pain in the inner right thigh radiating to the knee caused by a cystic endometriotic mass in the obturator internus muscle with nerve retraction…. Surgical removal of the mass was performed using the laparoscopic approach… A mass located within the right obturator internus muscle, below the right iliac external vein, behind the corona mortis vein, and lateral to the right obturator nerve was identified. The whole region was inflamed, and the nerve was partially involved. Dissection was performed carefully with rupture of the tumor, releasing a chocolate like fluid (Fig. 2), and the cyst was removed. Pathology examination was consistent with endometriosis. Patient improvement was observed, with pain relief and improved ability for right limb mobilization.” “The signs suggestive of intrapelvic nerve involvement include perineal pain or pain irradiating to the lower limbs, lower urinary tract symptoms, tenesmus or dyschezia associated with gluteal pain. Whenever deeply infiltrating lesions are present, the patient must be asked about those symptoms and specific MRI sequences for the sacral plexus must be taken, so that the equipment and team can be arranged and proper treatment performed.” “Before surgery, more women were affected by leg pain in the endometriosis group, compared to the control group (45.5% and 25.9%, respectively). Preoperative VAS scores for leg pain, however, were not significantly different between the two groups. A moderate correlation in the preoperative VAS scores between leg pain and dysmenorrhea was observed. After laparoscopy, we found a significant improvement in leg pain intensity in both groups. Conclusions: The prevalence of leg pain is increased in endometriosis, while leg pain intensity is not, compared to women without endometriosis. Laparoscopic surgery—even without preparation and decompression of nerve tissue—is associated with an improvement in pain intensity in women with endometriosis, as well as in the group without endometriosis.” “Pelvic floor dysfunction can also arise in response to other common chronic pain syndromes, such as endometriosis, irritable bowel disease, vulvodynia, and interstitial cystitis. A prospective evaluation of patients with chronic pelvic pain of various etiologies found abnormal musculoskeletal findings in 37%, versus 5% of controls.7 For this reason, the pelvic floor should be included in any evaluation regardless of the suspected source of pelvic pain.”

References Foti, P. V., Farina, R., Palmucci, S., Vizzini, I. A. A., Libertini, N., Coronella, M., … & Milone, P. (2018). Endometriosis: clinical features, MR imaging findings and pathologic correlation. Insights into imaging, 9(2), 149-172. Retrieved from https://link.springer.com/article/10.1007/s13244-017-0591-0 Vilos, G. A., Vilos, A. W., & Haebe, J. J. (2002). Laparoscopic findings, management, histopathology, and outcomes in 25 women with cyclic leg pain. The Journal of the American Association of Gynecologic Laparoscopists, 9(2), 145-151. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/S1074380405601223

3 years ago Symptoms No comment

Pain with Penetration

Pain with any type of penetration, such as from a tampon or from a physical exam, is a symptom of endometriosis. Pain may often be felt with sexual activity. Pain can be from pulling or stretching of tissue. It can also be from pelvic floor dysfunction or other problems with the muscles and ligaments of the pelvic floor. Physical therapy can be useful for this symptom. 

“Dyspareunia is the medical term for pain during sex. It frequently occurs in people with endometriosis because penetration and other movements associated with intercourse can stretch and pull the endometrial growths…. Penetration and other movements related to intercourse can pull and stretch endometrial tissue, particularly if it has grown behind the vagina or lower uterus. Vaginal dryness can also cause this pain. Some means of addressing endometriosis, such as hormonal treatments or a hysterectomy (surgical removal of the uterus), can cause dryness…. Those who do may experience the following:

  • pain that is acute or feels like stabbing
  • pain deep in the abdomen
  • pain ranging from mild to severe

“This pain varies from person to person and may depend on the type of intercourse. Some experience pain only during deep penetration, for example, while others experience pain after sex, rather than during it.” 

Links:

Studies:

  • Melis, I., Litta, P., Nappi, L., Agus, M., Melis, G. B., & Angioni, S. (2015). Sexual function in women with deep endometriosis: correlation with quality of life, intensity of pain, depression, anxiety, and body image. International Journal of Sexual Health, 27(2), 175-185. Retrieved from https://www.tandfonline.com/doi/full/10.1080/19317611.2014.952394 

“The study evidenced that deep endometriosis has a significant impact on sexuality and body image.”

  • Williams, C., Hoang, L., Yosef, A., Alotaibi, F., Allaire, C., Brotto, L., … & Yong, P. J. (2016). Nerve bundles and deep dyspareunia in endometriosis. Reproductive Sciences, 23(7), 892-901. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/26711313

“This study provides evidence that neurogenesis in the cul-de-sac/uterosacrals may be an etiological factor for deep dyspareunia in endometriosis.”

3 years ago Symptoms No comment

Pelvic Floor Dysfunction links

Studies:

“Unlike in pelvic floor disorders caused by relaxed muscles (eg, pelvic organ prolapse or urinary incontinence, both of which often are identified readily), women affected by nonrelaxing pelvic floor dysfunction may present with a broad range of nonspecific symptoms. These may include pain and problems with defecation, urination, and sexual function, which require relaxation and coordination of pelvic floor muscles and urinary and anal sphincters.”

Links to Pelvic Floor Dysfunction Resources:

3 years ago Symptoms No comment

Location of lesions and where pain is felt

Endometriosis lesions in different locations may cause different symptoms. Often the symptoms are referred pain (pain in a different place than where the endometriosis lesion is located). There is also some information about central sensitization. 

Overview

  “Clinical manifestations depend on the anatomic locations of the disease.

  • Bladder: dysuria, gross hematuria during menses, irritative voiding symptoms, urgency, frequent urination, urinary storage symptoms, tenesmus, burning sensation, suprapubic discomfort and pain, urinary incontinence [2, 3, 15].
  • Ureters: dysmenorrhea, dyspareunia, urinary symptoms, hydronephrosis, flank pain, decline of renal function [2, 3].
  • Round ligaments: painful, palpable inguinal mass (extra-pelvic portion of the ligaments); nonspecific pelvic pain (intra-pelvic portion) [11].
  • Retrocervical region and uterosacral ligaments: severe and painful symptoms, dyspareunia [3].
  • Vagina: dysmenorrhea, dyspareunia, postcoital spotting, prolonged menstruation not responding to medical therapy leading to anaemia [3, 16].
  • Rectosigmoid colon: cyclic pain during defecation, dyschezia, cyclic hematochezia, bloating, constipation, bowel cramping, catamenial diarrhoea, pencil-like stools, bowel obstruction [2, 3, 12, 17].
  • When unusual locations outside the pelvis occur, the pain may be site specific.
  • Thoracic-diaphragmatic endometriosis: chest pain (diffuse or basithoracic) with right-sided predominance, scapular or cervical pain associated with menses, sometimes radiating to the arm, pneumothorax, dyspnea, hemoptysis [18–20].
  • Sciatic nerve: cyclic sciatica, back pain, gluteal pain radiating to the dorsal thigh and lateral lower leg, positive Lasègue’s sign, sensory loss, reflex alterations, muscle weakness, paresis [2, 21–23].”
  • Riazi, H., Tehranian, N., Ziaei, S., Mohammadi, E., Hajizadeh, E., & Montazeri, A. (2015). Clinical diagnosis of pelvic endometriosis: a scoping review. BMC women’s health, 15(1), 39. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450847/pdf/12905_2015_Article_196.pdf 

“Clinical diagnosis by signs obtained from physical examination: Clinical signs of the disease that identified by physical examination (pelvic examination by inspection and palpation) included a broad range of signs. External genitalia and the vaginal surface were usually unremarkable [15]. Findings of physical examination are listed as follows:

  • External genitalia: Visible red, blue, or hemorrhagic nodules on the external genitalia [21].
  • Vagina: Visible red, blue, or hemorrhagic nodules on the vagina, and tender masses, nodules, and fibrosis on palpation of the upper vagina [8,15-17,21].
  • Cervix: Visible lesions on the cervix, tenderness on cervical movement, lateral cervical displacement, and cervical stenosis [15,16,19,21,37].
  • Uterus: A fixed (decreased or absent mobility) and retroverted uterus, and uterine motion tenderness in pelvic examination [8,15-17,19,21,24].
  • Adnexa: Tender or fixed adnexal masses resulting from endometriomas, adnexal enlargement, and pelvic masses [8,14,17,19,21].
  • Posterior vaginal fornix: Tender nodules in the posterior vaginal fornix, bluish implants typical of endometriosis or red, hypertrophic lesions bleeding on contact [15,17].
  • Pouch of Douglas: Fullness or mass or nodularity or pain in the pouch of Douglas, local tenderness or palpable tender nodules in cul de sac [8,14,16,19,30].
  • Rectovaginal septum: Tender masses, nodules, and fibrosis of the rectovaginal septum [15,19-21,37].
  • Uterosacral ligament: Thickening, pain or tenderness or nodularity in uterosacral ligament [8,14-16,19,21,24,30].”
  • Demco, L. (2000). Review of pain associated with minimal endometriosis. JSLS: Journal of the Society of Laparoendoscopic Surgeons, 4(1), 5. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3015350/ 

“What is most interesting is that right-left orientation of the pelvis does not exist in some patients. That is to say, palpation of a lesion of endometriosis on the left side of the pelvis may produce pain that the patient perceives as being on the right side of the abdomen, and the opposite is also true.”   

Low back pain and Sciatic nerve pain (sciatica)

  • Case Study of Sciatic Endometriosis:

Possover, M. (2017). Five-year follow-up after laparoscopic large nerve resection for deep infiltrating sciatic nerve endometriosis. Journal of minimally invasive gynecology, 24(5), 822-826. Retrieved from https://www.jmig.org/article/S1553-4650(17)30260-1/fulltext?fbclid=IwAR1OzlK62hXEY-TFBIx9flq10cgSjxLLyTOUAMqp0zyo3FBW3v2fgqE3dGA 

“In deep infiltrating intraneural endometriosis of the sciatic nerve, patients present with motor disorders before and after surgical resection. The average VAS score was reduced from 9.33 preoperatively to 1.25 at a 3-year follow-up. When full resection of endometriosis including nerve resection is completed, sciatic nerve function recover, but recovery of a normal gait may take at least 3 years and intensive physiotherapy.”

  • Case study of Sciatica and Back pain due to endometriosis:

Uppal, J., Sobotka, S., & Jenkins III, A. L. (2017). Cyclic sciatica and back pain responds to treatment of underlying endometriosis: case illustration. World Neurosurgery, 97, 760-e1. Retrieved from https://doi.org/10.1016/j.wneu.2016.09.111 

“We report on a 39-year-old gymnast with cyclic sciatica and back pain, whose initial presentation initially led to a spinal fusion at L4/5 and L5/S1, but that procedure did not change her symptoms. Her diagnosis of endometriosis was not made until 2 years after her spinal fusion. Ultimately, once diagnosed with endometriosis of the retroperitoneal spinal and neural elements, her back and leg pain responded completely to hormonal therapy and then to a hysterectomy and a bilateral salpingo-oophorectomy. Because her true diagnosis of endometriosis was unknown and she had some degenerative changes in her spine, she underwent a spinal fusion that would probably not have been done if the diagnosis of endometriosis had been suggested.”

  • Case Study Low Back Pain due to spinal endometriosis:

Dongxu, Z., Fei, Y., Xing, X., Bo-Yin, Z., & Qingsan, Z. (2014). Low back pain tied to spinal endometriosis. European Spine Journal, 23(2), 214-217. Retrieved from https://pubmed.ncbi.nlm.nih.gov/24531988/ 

“A 33-year-old woman presented with severe low back pain. She had the low back pain periodically for 3 years, and the pain was associated with menstruation. Radiographs showed a lesion in the posterior L3 body. After surgery, tissue biopsy indicated the presence of endometrial tissue in the lesion and thus confirmed endometriosis.”

Links:

3 years ago Symptoms No comment

Pain Associated with Minimal Endometriosis

“Minimal” endometriosis does not mean minimal pain. In fact, the opposite may be true- “minimal”, smaller lesions can produce a large number of prostaglandins that can lead to major pain. While this is an older study and “microscopic” endometriosis is debated, it is an interesting study demonstrating the appearance of lesions and the related pain felt. The research was done using laparoscopy under IV conscious sedation. Researchers identified that more pain was felt by the patient for some colors of lesions versus other colors. They also discovered that palpation of the endometriosis lesions produced the pain of cramps, not the uterus. Location of the endometriosis lesions in certain areas reproduced pain in other areas of the body, such as lesions on the utero-sacral ligaments lead to cramps in the back or those on the side wall of the pelvis led to pain radiating down the leg.

Links:

Study:

“A simple analogy that is often used to explain endometriosis to the patient is the example of the eyelash and the eye. The eyelash is a “normal” part of the eye and quite separate from the eyeball. Should a “normal eyelash” be placed on a “normal” eyeball, the eye becomes red with dilated corkscrew vessels. The eye becomes painful but continues to function, though not optimally. The eyeball returns to its normal state once the eyelash is removed. The body reacts in a similar manner when the “normal peritoneum” is exposed to the “normal endometrial tissue.” The peritoneal lining develops red lesions with dilated corkscrew vessels and becomes painful. The pelvic organs continue to function but not optimally, which can lead to infertility. The way to cure the problem is to find and remove the “normal endometrial tissue.” Although this analogy is not perfect, the patients seem to grasp the concept, since they have all experienced an eyelash in the eye scenario….

“Initial work on mapping of pain associated with the endometriosis lesions resulted in some thought-provoking findings. The classic black lesions were found to be painful in only 11% of patients when the lesion was touched. Similarly, white lesions were painful in 20% of patients with red lesions at 37%, and clear lesions at 32% were the most painful (Table 1). These results added further reason as to why initial therapy had such poor results. Surgeons would only “see” the black lesions and removed them, but these were the least painful lesions. The most painful clear lesions were not “seen” at laparotomy and therefore remained, as did the pain. What became apparent next, while mapping the patient, was the fact that the pain extended 28 mm beyond the visible border of the lesion onto what looked like “normal” peritoneum… 

“…Palpation of the lesions of endometriosis produced the cramps, not the uterus. Patients, postoperatively, reported that once they identified the cramps of endometriosis, they noticed that they were different than menstrual cramps. Furthermore, palpation of the endometriosis lesions on patients without a uterus and both ovaries removed reproduced the cramps of endometriosis. This confirmed the findings of other researchers who have concluded that a hysterectomy often does not change the course of the pain of endometriosis since it is the lesions, not the uterus, which are responsible for the cramp-like pain. The location of the lesion in relationship to the pelvis can, in most instances, reproduce the symptoms the patient experiences. Lesions on the utero-sacral ligament, when palpated, cause pain or cramps in the back. Palpation of lesions on the side wall of the pelvis result in pain or cramps radiating down the leg.

“What is most interesting is that right-left orientation of the pelvis does not exist in some patients.12 That is to say, palpation of a lesion of endometriosis on the left side of the pelvis may produce pain that the patient perceives as being on the right side of the abdomen, and the opposite is also true. How many times has a laparoscopy under general anesthesia been done on a patient complaining of right-sided pain where the surgeon saw a normal looking pelvis on the right—only to wake up the patient and tell her, “I saw nothing on the right side of your pelvis that would cause your pain.”

“The data revealing the failure of the approach of “treat and see,” based on what the surgeon observed at laparoscopy under general anesthetic, is strong and reveals that a new approach is needed. An approach based on patient confirmed diagnosis and patient-based analysis of the results of therapy needs to be looked at in greater detail. The only person who knows where the pain starts and ends is the patient herself. She is also the only one who can confirm when the pain is no longer present.”                     

3 years ago Symptoms No comment

What influences pain levels?

Some women might experience minimal pain with endometriosis, while many experience may experience severe pain. Bloski and Pierson (2008) state that “women with minimal or mild endometriosis have been found to have high degrees of pain and infertility, while asymptomatic women have been diagnosed with Stage IV on laparoscopy for tubal ligation. The variability in clinical presentation and stage of disease likely reflects of our lack of understanding of the pathophysiology of endometriosis.” Pain is influenced by several factors- the location of the endometriosis, the “type” or “stage” (clear, black, red, etc) of lesions, how much innervation is there, how much inflammatory chemicals are being released, if adhesions are pulling on anatomy, if other conditions such as pelvic floor dysfunction, interstitial cystitis, or adenomyosis is present. Pain with endometriosis is multifactorial, including irritation of nerves in the pelvis, new nerve growth, heightened sensitivity to pain, inflammation in the pelvis, and pain producing agents in the pelvic fluid (Ferrero, Vellone, & Barra, 2019). Interesting is that one study, from 1986, demonstrates evidence from many years ago, yet misinformation and misconceptions still exist! Differences that could influence pain levels:

“The three most commonly suggested mechanisms for pain production in endometriosis are [1] production of substances such as growth factors and cytokines by activated macrophages and other cells associated with functioning endometriotic implants (7, 8); [2] the direct and indirect effects of active bleeding from endometriotic implants; and [3] irritation of pelvic floor nerves or direct invasion of those nerves by infiltrating endometriotic implants, especially in the cul-de-sac (8, 9). It remains plausible that in any individual more than one or all of these mechanisms may be in operation. The neural irritation or invasion hypothesis has gathered much support in the past decade. Tender nodularity in the region of the cul-de-sac and the areas of the uterosacral ligaments has approximately 85% sensitivity and 50% specificity for the diagnosis of infiltrative endometriosis (10). Women with such findings on pelvic examination may have deep dyspareunia and more severe dysmenorrhea. Those with infiltration of the uterosacral ligaments and/or diseases directly adjacent to or invading the rectal wall may have dyschezia (9). The intensity of pain associated with infiltrative disease has been correlated with the depth of penetration of the lesion. The most severe pain is seen when the disease extends ≥6 mm below the peritoneal surface (10). Both perineural inflammation and direct infiltration of nerves by endometriosis have been observed (11). However, these kinds of perineural changes have been observed most commonly in women with central pelvic disease (i.e., around the uterosacral ligaments and in the cul-de-sac and not in those with lateral peritoneal or ovarian endometriosis).”

*Dyspareunia- pain with intercourse, dysmenorrhea- pain with menstruation, dyschezia- pain or straining with defecation

  • Vernon, M. W., Beard, J. S., Graves, K., & Wilson, E. A. (1986). Classification of endometriotic implants by morphologic appearance and capacity to synthesize prostaglandin F. Fertility and sterility, 46(5), 801-806. Retrieved from https://www.fertstert.org/article/S0015-0282(16)49814-6/pdf 

“The severity of the symptoms of endometriosis has not always correlated well with the anatomic severity of the disease. This lack of correlation may be due to variations in the metabolic activity of the endometriotic implants present at different stages of the disease. Because prostaglandin F (PGF) has been implicated as a hormonal mediator of the clinical symptoms of endometriosis, PGF synthesis and content was measured in implants from 14 patients with mild, moderate, severe, or extensive disease. To assess whether PGF production was related to the status of implants, the authors classified implants, based on gross and histologic criteria, as (1) petechial or reddish; (2) intermediate or brown; or (3) powder-burn or black. PGF production of implants from patients with mild or moderate disease was greater than that of implants from patients with severe or extensive disease (P < 0.05), and PGF content was similar for all stages of endometriosis. Petechial implants produced twice the amount of PGF than intermediate implants (P < 0.05), which in turn produced more PGF than powder-burn implants (P < 0.05). Powder-burn implants did not have the in vitro capacity to produce PGF, and the amount of PGF contained in implants of all classes was similar. Therefore, endometriotic implant PGF production and possibly other biochemical activities are dependent on the physical status of the implant. The classification of implants by morphologic appearance may afford additional assistance in determining the prognosis of the disease and in the examination of the subtle effects of the disease on symptoms.”

  • Wang, Y. Y., Leng, J. H., Shi, J. H., Li, X. Y., & Lang, J. H. (2010). Relationship between pain and nerve fibers distribution in multiple endometriosis lesions. Zhonghua fu chan ke za zhi, 45(4), 260. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20646536 

“There was significantly different distribution of nerve fibers in multiple endometriosis lesions, which was correlated with dysmenorrhea, anus pain, dyspareunia and chronic pelvic pain, not with clinical staging.”

  • McKinnon, B., Bersinger, N. A., Wotzkow, C., & Mueller, M. D. (2012). Endometriosis-associated nerve fibers, peritoneal fluid cytokine concentrations, and pain in endometriotic lesions from different locations. Fertility and sterility, 97(2), 373-380. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22154765 

“The presence of endometriosis-associated nerve fibers appear to be related to both the pain experienced by women with endometriosis and the concentration of PF cytokines; however, this association varies with the lesion location.”

  • Wang, G., Tokushige, N., & Fraser, I. S. (2011). Nerve fibers and menstrual cycle in peritoneal endometriosis. Fertility and sterility, 95(8), 2772-2774. Retrieved from https://pubmed.ncbi.nlm.nih.gov/21334610/ 

“There was no difference in the density of nerve fibers across the menstrual cycle in peritoneal endometriotic lesions. These findings may explain why patients with peritoneal endometriosis often have painful symptoms throughout the menstrual cycle.” 

“Position and depth of invasion of endometriotic implants greatly impacts the procedure performed. Deeply infiltrating endometriosis (DIE) consists of endometriotic nodules that invade greater than 5mm into the peritoneal or organ surface. The type of pelvic pain is correlated to the location of the DIE implants and can aid in pre-operative assessment of each patients individualized symptoms (1). Patients with DIE are more likely to have noncyclic CPP, most likely related to the infiltration of subperitoneal or visceral nerves by the implant. This is facilitated by activation of prostaglandins and chemokines associated with local angiogenic and neurogenic environments. This is thought to increase C-type nerve fibers and increase sensation of CPP due to the constant inflammatory state that endometriosis creates (15). The stroma of these lesions expresses receptors for nerve growth factor (NGF), which aids in recruitment of sensory nerve fibers (16). This increase in innervations allows for further pain perception in affected individuals. The increase in these nociceptors is further enhanced by sensitization with estrogen, which is found in abundance due to local implant estradiol (E2) production.”

*angiogenic- forms new blood vessels, neurogenic- forms new nerves, nociceptors-pain receptors

“The pelvis is highly vascularized and enervated, which is why pain impulses from this region are processed and sent to the brain. This, along with multiple other factors, contributes to the pain syndrome that is associated with endometriosis. Peritoneal fluid in women with endometriosis contains high levels of nerve growth factors that promote neurogenesis, the ratio of sympathetic and sensory nerve fibers is significantly altered within endometriotic tissue, and the nerve density within endometriotic nodules is increased.7,8 Also, the cytokines and prostaglandins produced by mast cells and other inflammatory cells attracted to ectopic endometrial-like tissue can activate nerve fibers and can trigger nearby cells to release inflammatory molecules.5,6,8,9

“Another source of pain is nerve fiber entrapment within endometriotic implants.4 The cyclical sciatic pain, weakness, and sensory loss can all stem from endometriotic entrapment of the sciatic, femoral, or lumbosacral nerve roots.9 There are numerous descriptions of sacral radiculopathy occurring in patients with endometriosis, and there are even descriptions of wheelchair-bound patients becoming fully ambulatory after treatment of infiltrative endometriosis.9

“Central sensitization is another mechanism that promotes endometriosis-associated pain. Patients become highly sensitive to subsequent painful stimuli because of endometriosis-induced neuroplastic changes in descending pathways that modulate pain perception.10 In response to a subsequent insult (ie, nephrolithiasis or peritoneal organ injury), women can experience pain from endometriosis as a result of inability to engage descending inhibition pathways.”

“Initial work on mapping of pain associated with the endometriosis lesions resulted in some thought-provoking findings. The classic black lesions were found to be painful in only 11% of patients when the lesion was touched. Similarly, white lesions were painful in 20% of patients with red lesions at 37%, and clear lesions at 32% were the most painful (Table 1). These results added further reason as to why initial therapy had such poor results. Surgeons would only “see” the black lesions and removed them, but these were the least painful lesions. The most painful clear lesions were not “seen” at laparotomy and therefore remained, as did the pain. What became apparent next, while mapping the patient, was the fact that the pain extended 28 mm beyond the visible border of the lesion onto what looked like “normal” peritoneum ((Figure 1). Therefore, if the surgeon only removed the lesion at its border, the microscopic disease in the previously identified normal looking peritoneum was left, and persistence or recurrence of the symptoms was encountered.” 

  • Fraser, I. S. (2010). Mysteries of endometriosis pain: Chien‐Tien Hsu Memorial Lecture 2009.Journal of Obstetrics and Gynaecology Research, 36(1), 1-10. Retrieved from https://pubmed.ncbi.nlm.nih.gov/20178521/  “The more that one looks at the condition endometriosis, the more one realises that it is a unique and complex condition exhibiting a bizarre range of deviations from normal endometrial and myometrial physiology, and presenting with a challenging range of pain‐related symptoms. The changing nature of the pain is not well defined, and the molecular mechanisms leading to pain generation are far from clear. Recent research has begun to reveal some of these links between expression of unusual molecules in the eutopic endometrium and ectopic lesions, microanatomical changes in the pelvic nervous sytem, neuronal dysfunction and the later development of neuropathic pain.” 
  • Miller, E. J., & Fraser, I. S. (2015). The importance of pelvic nerve fibers in endometriosis. Women’s health, 11(5), 611-618. Retrieved from https://pubmed.ncbi.nlm.nih.gov/26314611/

“Several lines of recent evidence suggest that pelvic innervation is altered in endometriosis-affected women, and there is a strong presumption that nerve fibers demonstrated in eutopic endometrium (of women with endometriosis) and in endometriotic lesions play roles in the generation of chronic pelvic pain. The recent observation of sensory C, sensory A-delta, sympathetic and parasympathetic nerve fibers in the functional layer of endometrium of most women affected by endometriosis, but not demonstrated in most women who do not have endometriosis, was a surprise. Nerve fiber densities were also greatly increased in myometrium of women with endometriosis and in endometriotic lesions compared with normal peritoneum. Chronic pelvic pain is complex, and endometriosis is only one condition which contributes to this pain. The relationship between the presence of certain nerve fibers and the potential for local pain generation requires much future research.” 

“Our group discovered that ectopic growths harvested from ENDO rats and women with established endometriosis develop their own C-fiber (sensory afferent) and sympathetic (autonomic efferent) nerve supply. The supply is derived from nerve fibers innervating nearby territories that sprout branches into the growths [10], [11]. This discovery suggests that, rather than the growths alone, it is the ectopic growth’s own innervation that is a major contributor to the maintenance and modulation of pain in established endometriosis.” 

  • Anaf, V., Chapron, C., El Nakadi, I., De Moor, V., Simonart, T., & Noël, J. C. (2006). Pain, mast cells, and nerves in peritoneal, ovarian, and deep infiltrating endometriosis. Fertility and sterility, 86(5), 1336-1343. Retrieved from https://doi.org/10.1016/j.fertnstert.2006.03.057 

“The presence of increased activated and degranulating mast cells in deeply infiltrating endometriosis, which are the most painful lesions, and the close histological relationship between mast cells and nerves strongly suggest that mast cells could contribute to the development of pain and hyperalgesia in endometriosis, possibly by a direct effect on nerve structures.” 

“The objective of this study was to evaluate the significance of severe preoperative pain for patients presenting with ovarian endometrioma (OMA)…. After multiple logistic regression analysis, uterosacral ligaments involvement was related with a high severity of chronic pelvic pain [odds ratios (OR) = 2.1; 95% confidence interval (CI): 1.1–4.3] and deep dyspareunia (OR = 2.0; 95% CI: 1.1–3.5); vaginal involvement was related with a higher intensity of lower urinary symptoms (OR = 13.4; 95% CI: 3.2–55.8); intestinal involvement was related with an increased severity of dysmenorrhoea (OR = 5.2; 95% CI: 2.7–10.3) and gastro-intestinal symptoms (OR = 7.1; 95% CI: 3.3–15.3). CONCLUSIONS: In case of OMA, severe pelvic pain is significantly associated with deeply infiltrating lesions. In this situation, the practitioner should perform an appropriate preoperative imaging work-up in order to evaluate the existence of associated deep nodules and inform the patient in order to plan the surgical intervention strategy.”

“In the brain stem, the neurotransmitters serotonin and norepinephrine modulate pain transmission through ascending and descending neural pathways. Both serotonin and norepinephrine are also key neurotransmitters involved with the pathophysiology of depression. Tricyclic antidepressants are effective treatments for pain and depression; selective serotonin reuptake inhibitors provide less benefit. Duloxetine and venlafaxine, which are serotonin and norepinephrine reuptake inhibitors, were shown in clinical trials to alleviate pain and depressive symptoms. Diabetic neuropathy and other chronic pain syndromes were also shown to benefit from duloxetine and venlafaxine. Antidepressants remain fundamental therapeutic agents for depression and anxiety disorders. Their extended use into chronic pain, depression with physical pain, physical pain with or without depression, and other potential medical conditions should be recognized.”

  • Grundström, H., Gerdle, B., Alehagen, S., Berterö, C., Arendt‐Nielsen, L., & Kjølhede, P. (2019). Reduced pain thresholds and signs of sensitization in women with persistent pelvic pain and suspected endometriosis. Acta obstetricia et gynecologica Scandinavica, 98(3), 327-336. Retrieved from https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/aogs.13508

“Women with pelvic pain and suspicion of endometriosis should probably be treated more thoroughly to prevent or at least minimize the concomitant development of central sensitization.”

Links:

  • “Hormones and chemicals released by endometriosis tissue also may irritate nearby tissue and cause the release of other chemicals known to cause pain….Some endometriosis lesions have nerves in them, tying the patches directly into the central nervous system. These nerves may be more sensitive to pain-causing chemicals released in the lesions and surrounding areas. Over time, they may be more easily activated by the chemicals than normal nerve cells are. Patches of endometriosis might also press against nearby nerve cells to cause pain.” https://www.nichd.nih.gov/health/topics/endometri/conditioninfo/Pages/symptoms.aspx

Reference

Bloski, T., & Pierson, R. (2008). Endometriosis and chronic pelvic pain: unraveling the mystery behind this complex condition. Nursing for women’s health, 12(5), 382-395. doi: 10.1111/j.1751-486X.2008.00362.x

Ferrero, S., Vellone, V. G., & Barra, F. (2019). Pathophysiology of pain in patients with peritoneal endometriosis. Annals of translational medicine, 7(Suppl 1). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462618/

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