Affecting around 190 million women and girls globally, endometriosis is caused by the growth of tissue – similar to those in the uterine lining – outside the uterus, leading to debilitating pelvic pain during sex and periods – which is usually a heavy flow.
As 50% of endometriosis patients deal with fertility issues, the economic cost that the condition has on the U.S. alone – both in terms of medical care and lost productivity – is estimated to be around $78-120 billion annually, according to Bruce Nicholson, CSO and co-founder of Hera Biotech, a U.S.-based women’s health company that is developing endometriosis diagnosis tests.
Nicholson explained that despite this pervasive challenge to women’s health, patients suffer an average delay of 8 years for diagnosis, which can only be done reliably with surgery.
While hormonal therapy can help alleviate symptoms, it fails to address infertility. Moreover, the surgical removal of lesions is often temporary as the lesions return 50% of the time, according to Nicholson.
“A major reason why we do not yet have better options has been the chronic underfunding of research in this area. Similarly common diseases, like diabetes and breast cancer (affecting 12-15% of the population) receive 15 and 30 fold greater levels of funding from the NIH, respectively. Rarer and similarly non-lethal diseases like Crohn’s disease, receives 65 fold more funding per patient,” said Nicholson.
“Despite these limitations, we have seen some significant progress in the study of endometriosis over the last 5-10 years.”
As uncovering the complexity of the gut microbiome has been crucial to healing inflammatory diseases, an intriguing link between the microflora and endometriosis could look into potential drug targets to treat the condition.
“Real therapeutics to interrupt or prevent the disease itself will require much more extensive studies on the cellular pathophysiology underlying lesion formation, and the signaling pathways that lead to disease progression. This is the strategy that has led to great recent advances in cancer research but this will take a concerted change in research funding for endometriosis to match the extent and severity of this disease,” said Nicholson.
Presently, with various clinical trials showing promise and with the discovery of new drug targets, there is hope for endometriosis care. As we observed International Day of Action for Women’s Health on May 28, let us take a look at some of the recent advancements in endometriosis research.
Potential breakthrough drug to begin clinical trials soon
While treatment for endometriosis depends on factors like age and the extent of the symptoms, surgery and hormone treatment are typically the only options. And the fact that there hasn’t been a new treatment in 40 years, expresses how difficult-to-treat the disease can be. But now, that’s all about to change.
A new drug, dichloroacetate, has the potential to be the first ever non-hormonal and non-surgical treatment for endometriosis. Researchers from the University of Edinburgh found that when cells from the pelvic wall in people with endometriosis were treated with dichloroacetate, the amount of lactate that was produced prior to administering the drug, decreased. This is key to endometriosis treatment because amplified lactate production in these cells has been associated with the manifestation of endometriosis, according to an earlier study funded by Wellbeing of Women, a U.K.-based charity focused on reproductive and gynecological health. Dichloroacetate was able to reduce the size of endometriosis lesions, as a result.
Calling the prospective treatment long overdue, Janet Lindsay, chief executive of Wellbeing of Women, said: “Too many women and girls are suffering from debilitating symptoms, such as chronic pelvic pain, fatigue and even fertility problems, and current hormonal and surgical treatments aren’t suitable for everyone. Dichloroacetate has the potential to be the very first non-hormonal and non-invasive treatment for endometriosis, which will be truly ground-breaking.”
For advancing in clinical trials, £250,000 has been awarded by Wellbeing of Women and the Scottish Government to the Universities of Edinburgh, Aberdeen and Birmingham, the study’s main collaborators.
New research will explore cannabis as a treatment for endometriosis
Medical cannabis has been studied for its anti-inflammatory properties and is used to alleviate side effects caused by chemotherapy, and has been prescribed for treating epilepsy and multiple sclerosis. An upcoming clinical trial by the Western Sydney University in Australia will investigate its potential benefits for the treatment of endometriosis.
The research, for which the university will receive $660,000 from the Wilson Foundation, will look into the effect of cannabis on the cell-signaling endocannabinoid system (ECS), as well as inflammatory markers. The double-blind randomized controlled trial will evaluate whether medicinal cannabis – in the form of cannabidiol (CBD) isolate or a balanced oil containing both CBD and delta-9-tetrahydrocannabinol (THC) – can counter symptoms like pain caused by endometriosis against a placebo.
As 59% of women who used cannabis for endometriosis-related pain relief reported that they do not rely on pain killers anymore, the trial is based on evidence from an earlier study that revealed that cannabis can regulate inflammation and immune function, through interaction with the ECS.
“Various phytochemicals, mainly CBD, from cannabis have well described analgesic, anti-inflammatory, and antidepressant actions, and can also reduce anxiety and nausea. Cannabis use in other chronic pain conditions has resulted in a “substitution effect” of pharmaceuticals, commonly opioid analgesics, by cannabis,” said Mike Armour, principal investigator of the study, and associate professor at NICM Health Research Institute at Western Sydney University, who explained that people in Australia who have taken cannabis to deal with the condition’s symptoms found that it improved sleep and gastrointestinal functions.
“However, there is still a lot we don’t know about how or why cannabis may affect endometriosis symptoms and possibly slow lesion progression. The trial will allow us to determine the effective dosage range, ideal THC to CBD ratio, duration of treatment and so forth,” said Armour.
Harnessing the target potential of the ECS – which after the brain, the female reproductive system has the most endocannabinoid receptors – Israel-based startup Gynica is developing a cannabinoid-based therapy for treating symptoms of endometriosis like chronic menstrual pain and painful intercourse. Studies for the therapy are ongoing.
Drug candidate for endometriosis shows higher efficacy than current treatment in animal studies
Meanwhile, the discovery of an overexpressed protein on endometriotic cells by the startup Fimmcyte, based in the biotech startup hotspot of Basel, has fueled a potentially revolutionizing therapy for endometriosis.
This observed overexpression, wherein otherwise has low expression on the lining of the uterus and the rest of the body, has paved the way for a possible drug target, one that is currently being explored by Fimmcyte. The company is developing a highly specific antibody that labels the endometriosis cells for clearance by the immune system, according to Mohaned Shilaih, co-founder of FimmCyte.
Over the past 18 months, the young biotech performed several studies on mice where patient-derived material was implanted, and it was found that the treatment was “highly effective and reduced the disease burden,” according to Shilaih. Not only did the therapy demonstrate efficacy that was higher than treatment with gonadotropin-releasing hormone (GnRH) antagonist, which is the current standard of care, but it also did not affect the hormonal balance, cycle, and ovarian weight in the mice.
Shilaih said: “Endometriosis affects one in 10 women globally, with more than 30% reporting dissatisfaction with hormonal and/or surgical interventions due to the side effects and lack of efficacy. FimmCyte’s treatment will provide a much needed non-hormonal therapy for women with endometriosis that could be safe and effective without undesirable side-effects.”
The company aims to continue research into its therapy and acquire funding for Investigational New Drug / Clinical Trial Authorization (IND/CTA) enabling studies, and hopes to begin clinical trials in 2025.
Managing endometriosis: the benefits of pelvic floor therapy
As there is abundant research that proves the effectiveness of physiotherapy for the rehabilitation of the pelvic floor for those who have bowel and bladder issues and for childbirth recovery, recent studies have shown that it could be key to tackling endometriosis-induced pain, which has been described as a sharp, stabbing sensation.
A 2021 study showed that upon incorporating pelvic floor therapy as part of their lifestyle, 17 women with deeply infiltrative endometriosis (DIE) – a type of endometriosis that can invade the organs near the uterus – showed increased levator hiatal area, which was observed in an ultrasound. The levator hiatal area is a region associated with the pelvis and is the largest potential hernial portal. The results led to pelvic floor relaxation, improved superficial dyspareunia – which causes pain at the vaginal opening during sex – as well as helped manage chronic pelvic pain.
Since then, pelvic floor therapy for patients with endometriosis has led the way for pain management for endometriosis and other pelvic pain-related issues – with around 80% of chronic pelvic pain being caused by endometriosis.
A more recent review also confirmed the effects of physiotherapy for treating endometriosis pain. Physiotherapy for patients with endometriosis includes kinesiotherapy, physical therapy and balneology. These measures have been effective in relieving pain through exercise and movements targeting the pelvic area.
Correlation between endometriosis and other inflammatory diseases found
As inflammation has been known to trigger endometriosis-related cell proliferation, recent research has found that the condition may be linked to other inflammatory as well as pain-inducing diseases.
“Several labs around the world have collaborated in genome wide sequencing studies to identify variants associated with endometriosis. This study mainly identified changes in later stage endometriosis associated with pain and inflammation, both consequences, but not causes of, endometriosis,” said Nicholson.
The collaborative study by U.S.-based biotech Celmatix and genomics company 23andMe along with other researchers, was a genome-wide association study meta-analysis of 60,674 cases and 701,926 controls of people of European and East Asian descent. 42 genome-wide significant loci comprising 49 distinct association signals were identified which explained up to 5.01% of disease variance and methylation of genes in endometrium and blood, many of which were associated with pain perception, according to the study.
The research found that endometriosis may be linked to 11 conditions including migraine, back and multisite chronic pain (MCP), and inflammatory conditions like asthma and osteoarthritis.
Further research could explore potential drug targets which could expedite interventions for not just endometriosis but other chronic pain-inducing conditions as well.
New technologies related to endometriosis
- Multi-level Structured Program for the Treatment of Endometriosis – Puerto Rico Science, Technology & Research Trust
- Reducing the Progression of Endometriosis with Short Treatment of Corticotropin-Releasing Hormone Receptor Antagonist – Puerto Rico Science, Technology & Research Trust