Endometriosis: Causes and the important role of the endocannabinoid system (part 2)

UncategorizedWomen's health Jul 2022

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About the causes and symptoms of endometriosis and why the endocannabinoid system plays a promising role in the treatment of endometriosis

Endometriosis (EM) affects many women during their reproductive years and is associated with pain and infertility, which can also affect psychological well-being and quality of life. EM is a common condition. Characteristically, tissue that resembles the tissue that normally lines the inside of the uterus – called the endometrium – grows outside the uterus.

The endometrial-like tissue outside the uterus reacts to hormonal stimuli and behaves like endometrial tissue: it thickens, breaks down and bleeds with each menstrual cycle. However, since this tissue cannot leave the body, it becomes trapped and leads to internal bleeding, inflammation and fibrosis. The surrounding tissue can also become irritated, eventually forming scar tissue and adhesions that can cause pelvic tissues and organs to stick together. These changes are associated with chronic and often debilitating cyclical pain and infertility. 

Theories about the causes of endometriosis

Although the exact cause of endometriosis is not yet known, there are various theories:

Retrograde menstruation

In retrograde menstruation, menstrual blood containing endometrial cells flows back through the fallopian tubes into the pelvic cavity instead of leaving the body. These endometrial cells remain attached to the pelvic walls and the surfaces of the pelvic organs, where they grow and continue to thicken and bleed during each menstrual cycle.

Conversion of abdominal peritoneal cells

In the so-called “induction theory”, experts assume that hormones or immune factors promote the transformation of peritoneal cells – cells that line the inside of the abdomen – into endometrial-like cells.

Conversion of embryonic cells

Hormones like oestrogen can turn embryonic cells – cells in the earliest stages of development – into endometrial-like cell implants during puberty.

Surgical scars

After surgery, e.g. a hysterectomy or caesarean section, endometrial cells can become attached to a surgical incision.

Transport of endometrial cells

The blood vessels or the tissue fluid system (lymphatic system) can transport endometrial cells to other parts of the body.

Disturbance of the immune system

A problem with the immune system can lead to the body not being able to recognise and destroy endometrial-like tissue that grows outside the uterus.

Unfortunately, none of these theories fully explains why endometriosis occurs. It is likely that a combination of factors causes the disease.

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Symptoms and treatment of endometriosis

The main symptom of endometriosis is pelvic pain, which often accompanies menstruation and is called dysmenorrhoea. Although many women experience cramps during their menstruation, sufferers describe menstrual pain that is much more severe than normal. Other common signs and symptoms of endometriosis include painful sexual intercourse (dyspareunia), pain during bowel movements or urination, excessive bleeding and infertility. 

Due to the multi-layered pathogenesis, the treatment of pain in EM patients is a medical challenge. EM-associated pain mechanisms are complex and interrelated and can be divided into three main categories: nociceptive, inflammatory and neuropathic pain.

Current pain management strategies for EM focus mainly on medical treatments with a single mechanism of action, such as hormone therapy, analgesics or non-steroidal anti-inflammatory drugs (NSAIDs) and/or surgical resections. For this reason, current medical treatment is inadequate as it is associated with a high likelihood of recurrence of symptoms and/or only partial relief of chronic pelvic pain.

In addition, EM pain is often associated with psychological problems and fatigue, which can further exacerbate the pain. Therefore, a multi-mechanism therapeutic approach is needed to treat the complex symptoms in EM patients. 

Endometriosis is associated with endocannabinoid deficiency

Endocannabinoids were only discovered in 1992 and have only recently been studied in detail. Endocannabinoids and their receptors are present throughout the body. The endocannabinoid system is ubiquitous in the female reproductive system and there is evidence that virtually all phases of female reproduction are regulated by ECS signalling. Cannabinoid receptors are present in the endometrium, myometrium, ovarian cortex, medulla and fallopian tubes. They influence the menstrual cycle, the maturation of the ovaries and the implantation of an embryo. 

The endocannabinoid system (ECS) has recently gained attention in the treatment of EM-related pain. Significant differences in the concentrations and expressions of the components of the ECS have been found in the endometrium of women with endometriosis compared to control subjects. Endometriosis seems to be associated with a reduced number of CB1 receptors and a higher number of CB2 and TRPV1 receptors. This alteration of the ECS components could trigger the nociceptive, inflammatory and neuropathic pain in EM.

In addition, the ECS in endometriosis has been shown to interact with specific mechanisms in the body associated with pain development, such as inflammation, cell proliferation and cell survival. These mechanisms play a crucial role in endometriosis-associated pain and in the development of the disease, its maintenance and its recurrence. 

The interactions between the ECS and pain-associated mechanisms in EM patients occur at multiple levels: Central and peripheral nervous system changes, involvement of neuropathic and inflammatory pain, psychological interaction with the pain experience, hormonal variability of pain, and expression of cannabinoid receptors, enzymes and ligands. Therefore, modulation of the ECS appears to be an excellent therapeutic strategy as it potentially combines all these factors. 

Effects of cannabis on EM-associated pain and related symptoms

Cannabis contains secondary compounds known as exogenous cannabinoids (e.g. THC and CBD). This class of natural compounds interacts with the ECS receptors in our body. Therefore, cannabis can be an effective option for alleviating various EM-related symptoms. For example, one of the main features of endometriosis is inflammation. Cannabis has anti-inflammatory properties. Another symptom of endometriosis is (often chronic) pain. Studies show that cannabis is helpful for chronic pain. Endometriosis can also cause accompanying symptoms such as anxiety and depression, which cannabis can also help with.

According to international surveys, cannabis is one of the most commonly used self-treatment strategies for endometriosis symptoms and reportedly has the highest self-rated efficacy in reducing pain among patients. However, the exact mechanism by which these agents may help is poorly understood. It is hoped that the research groups currently pioneering the field of cannabis endometriosis worldwide will further uncover the true background.

In a survey, EM clinical patients were asked about their experiences with cannabis and cannabidiol (CBD) for the treatment of endometriosis and pelvic pain symptoms. Most patients (67.5-75.9%) who had tried cannabis and/or CBD products reported that both cannabis and CBD were moderately or very effective for pelvic pain. An online cross-sectional survey in Australia found that 13 % of women with endometriosis use cannabis products to manage symptoms and pain. The reported effectiveness in reducing pain was so high that pharmaceutical medication, especially opioids, could be reduced by at least half for them. In addition, the women reported significant improvement in sleep problems, nausea and vomiting.

Another cross-sectional survey in New Zealand showed similar results, reporting that cannabis is an effective way to treat pain and other endometriosis symptoms and can replace opioid and painkiller use. Cannabis was most commonly used for pain relief and to improve sleep. Respondents reported that their symptoms were ‘much better’ for pain (81%), sleep (79%) and nausea or vomiting (61%). More than three quarters of respondents reported that cannabis reduced their normal medication use. More than half were able to stop taking other medications completely; analgesics and opioids were the most common class of painkillers that were reduced.

A recent observational study of women with recurrent EM showed the benefit of CBD on various EM symptoms after six months of oral/vaginal use. The use of CBD oils and CBD suppositories not only subjectively improved the patients’ quality of life, but also reduced pain intensity on the numerical rating scale. CBD also significantly improved sleep quality and other psychosomatic aspects.

In addition, the number of sick leaves decreased. The relaxing, anti-anxiety, analgesic and anti-inflammatory effects of CBD significantly improved the patients’ quality of life during the six months. Patients reported that CBD treatment improved self-assessment of physical and psychological well-being. These studies were selected from the growing body of evidence on the use of cannabis for symptom control in EM. Overall, the women reported good efficacy of cannabis in relieving pain and other symptoms, with few adverse side effects reported. 

However, the exact mechanism by which these substances may help is poorly understood and still being researched. Hopefully, the groups currently pioneering cannabis endometriosis treatment around the world will continue to uncover it.

The content of this article does not constitute or replace medical advice. It is important that you see your doctor if you have any health concerns and that you work with medical professionals to develop treatment plans that are right for you.

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