Written by Dr. Amy Zheng
Endometriosis is a complex, chronic, and painful condition affecting 10-15% of women of reproductive age. Depending on the severity, endometriosis can have profound effects on the lives of affected individuals. Yet, despite global awareness campaigns, endometriosis remains poorly understood, leading many women to suffer from under-diagnosis and ineffective treatment options.
What is endometriosis?
Endometriosis occurs when tissue that normally lines the inside of the uterus (the endometrium) travels outside and adheres to nearby organs. The displaced tissue triggers inflammation that can result in scar tissue and distortion of pelvic organs. In more advanced stages, ovarian cysts called endometriomas can form.
Endometriosis causes a range of symptoms, with debilitating menstrual pain being the most common. The pain can also occur from sexual intercourse as well as urination and bowel movements. Living with this ongoing pain severely affects women’s quality of life, interfering with their physical and mental well-being, sleep, work, school, and relationships.
Moreover, up to 50% of women with endometriosis experience infertility, and up to 50% of infertile women have been diagnosed with endometriosis.
Chronically underfunded
While its symptoms are numerous and hard to live with, research on endometriosis is poorly funded, ranking 266 out of 302 research and disease categories that were supported by the NIH in 2019. As a result, the pathophysiology of endometriosis is not well understood. There is currently no cure for endometriosis, and standard treatment options have limited effectiveness.
The treatments for endometriosis are restricted to hormonal therapies (e.g. birth control, gonadotropin-releasing hormone agonists) and surgery. While helpful in alleviating symptoms, hormonal remedies come with their own set of adverse side-effects and do not address the root cause of endometriosis or provide long-term results. The same can also be said for surgery, another less than ideal treatment for women with endometriosis. Conservative surgery aims to remove endometriotic lesions while preserving reproductive organs, but the recurrence rate is very high, reaching up to 50% at 5 years. Even a hysterectomy cannot guarantee complete symptom relief.
What’s worse is that the lack of funding that’s preventing effective treatments is also preventing insight into the direct cause of endometriosis. Surgery is currently the only way to definitively diagnose someone with the condition, and without more money and researchers to investigate endometriosis, a cause will be harder to find, making a cure more challenging to secure.
How genes shed insight on endometriosis
While the cause of endometriosis remains largely unknown, mounting evidence suggests an interplay between environmental and genetic factors. Twin studies have shown the approximate heritability of endometriosis to be ~50%. As such, multiple genes have been found to increase endometriosis risk.
Variations in genes associated with the immune response, for example, are frequently implicated in the development of endometriosis. The theory is that these genes contribute to the cells in the immune system’s ability to remove the ectopic endometrial tissue. One example is IL1A, which is involved in immune responses and is an essential inflammatory mediator. Another implicated gene is BLYS, which is crucial in the activation of the adaptive immune system.
Genes involved in the formation of the extracellular matrix, a complex network of proteins involved in cell-cell adhesion and structure, have also been linked to the development of endometriosis. This finding is likely due to variants that cause the endometrial cells to become more “invasive,” making them stick to other tissues. However, the genetic component of endometriosis doesn’t stop there.
Researchers believe increased exposure to estrogen is a risk factor for endometriosis. As a result, it is unsurprising that variation in estrogen receptor 1 (ESR1) is associated with a predisposition to developing the condition, as is the estrogen response gene GREB1.
There is also a critical question as to whether environmental factors, such as exposure to toxic chemicals, could contribute to endometriosis. However, when researchers found a potential link between polyhalogenated aromatic hydrocarbons and endometriosis in Rhesus monkeys, the question was answered. CYP1A1 is a gene that’s involved in the metabolism of such toxic chemicals, and variation in the gene is associated with the development of endometriosis.
Discovering a therapeutic treatment
More and more people with chronic illnesses are turning to natural remedies to supplement their treatment regimes. One such natural remedy is cannabis, which contains various compounds with antioxidant, analgesic, and anti-inflammatory properties.
While not typically discussed, cannabis’ therapeutic effects can alleviate common symptoms of endometriosis. The plant contains several phytocannabinoids and terpenes that can target four specific adverse effects of the condition.
1. Inflammation
Cannabidiol (CBD) is a famous non-psychoactive cannabinoid found in cannabis. It is associated with several health benefits and also has anti-inflammatory effects. In addition, THC, another primary cannabinoid found in cannabis plants, contains potent anti-inflammatory effects. The anti-inflammatory properties in both cannabinoids and terpenes such as myrcene, linalool, and limonene can provide immense relief for women with endometriosis, as inflammation is a painful consequence of the condition.
2. Pain
One of the dominant symptoms of endometriosis is chronic pain. CBD and THC have been shown to suppress pain through interaction with the glycine receptors of the central nervous system. As a result, both cannabinoids could be successful in treating pain and alleviating discomfort that women with endometriosis feel for weeks or months at a time.
3. Nausea
Many women with endometriosis suffer from nausea. This symptom likely occurs as a result of a combination of pain, poor sleep, anxiety, and low appetite. However, both CBD and THC have anti-nausea effects. The phytocannabinoids are frequently sought after by those going through chemotherapy to prevent nausea and vomiting. Various research studies also provide evidence of the compounds’ anti-nausea effect, which happens through their activation of the 5-HT1A receptors in the brain.
4. Sleep Issues
In addition to THC and CBD, terpenes are great solutions for regulating sleep, which women with endometriosis have trouble getting when they’re experiencing so much pain. Terpenes that have anxiety and sedative effects, like phytol and alpha-pinene, activate the brain’s GABA system to lower anxiety, increase calm, and promote sleep. Research studies also indicate that linalool increases adenosine, a sedating hormone that helps encourage sleep, and that limonene can help decrease symptoms of insomnia.
The dependence on natural solutions
Cannabis can represent a possible solution that alleviates some symptoms associated with endometriosis, without the negative side effects of conventional medication. The plant can target inflammation, relieve pain, reduce nausea, and improve sleep. Other potential outcomes could be a reduction in anxiety, improved appetite, and enhanced energy.
However, hopefully, in the future, research on the benefits of cannabis and the pathophysiology of endometriosis will provide new treatment options for affected women. Endometriosis is a debilitating condition for the women who experience it, and without proper funding, women will have to look for natural and creative solutions — like cannabis — to alleviate their symptoms.
Dr. Amy Zheng is a neuroscientist and co-founder of Strain Genie, a precision medicine startup leveraging genetic data to provide personalized cannabis recommendations. She received her Ph.D. from UCLA with emphasis in brain injury research and neuroimaging methodologies. Her published work can be found here.
