Endometriosis: diagnosing the “missed disease”

What is endometriosis?

Endometriosis is a condition that causes a build-up of endometrial-like cells outside of the uterus. In a healthy uterus, each month cells build up on the lining of the uterus forming the endometrium, preparing it for the potential of pregnancy. If this does not happen, the cells of the uterus lining break down and leave the body as a menstrual effluent (ME) – the period. The tissue that builds up for people with endometriosis thickens and breaks down throughout the menstrual cycle, becoming inflamed and forming endometriosis lesions, which causes a wide range of symptoms, as shown in Figure 1 (Source: Ellis K, Munro D, Wood R. The experiences of endometriosis patients with diagnosis and treatment in New Zealand. Front Glob Womens Health. 2022 Aug 31;3:991045. doi: 10.3389/fgwh.2022.991045).

Despite affecting 1 in 10 people with a uterus – roughly 1.5 million people in the UK alone ​– endometriosis is woefully understood and funded. This lack of information has resulted in many people struggling with their symptoms and the impact it has on their life, often for years while they await a diagnosis.  

These delays in diagnosis, coupled with a general lack of understanding of the condition, affects all areas of a patient’s life. One interviewee recalled: “I remember being at my Saturday job and having to go home because the pain was so bad, but on my way home I collapsed at the train station”.  

Clearly there is a need for better knowledge around endometriosis and the devices used for its diagnosis, treatment and management.

“I felt like a burden to the people in my life because I knew every month I would be in such pain and would be unable to do things.” Endometriosis patient

To make progress, it is important that we understand the journeys of people with endometriosis and how medical devices can support them. So, what are the experiences of people with this disease? Who are the people in the medical device industry innovating to improve its diagnosis, treatment and management? How can we hold the patients’ voices and experiences central to device developments and innovations? Below is a patient journey map that helps illustrate these issues: 

Endometriosis - the missed disease

The uncertainty surrounding endometriosis has led to excruciatingly long diagnosis time, which averages globally to between seven and nine years. As a result, endometriosis has been dubbed the “missed disease”. Considering that endometriosis can begin from a patient’s first period, the years taken to get a diagnosis can occur during formative years and have an impact on their wider life for a long time, with one interviewee highlighting “my diagnosis journey started early in my formative years – I missed out on so many experiences because of the pain… I was literally asking what is wrong with me?.”

So why is endometriosis the missed disease and how can medical devices tackle this?

Misdiagnosis

As mentioned above, endometriosis is a highly complex disease. This is compounded by the fact it shares symptoms with many other health conditions, meaning it can sometimes be misdiagnosed as conditions such as pelvic inflammatory disease (PID), ovarian cysts and irritable bowel syndrome (IBS). One patient was reportedly “misdiagnosed for over 10 years before finding out what was really going on.”

People with endometriosis are often more likely to also have other pelvic health conditions. One study found that 26% of patients with endometriosis also had fibroids, with another study suggesting there is a correlation between deep endometriosis and adenomyosis. These findings highlight the need for a holistic understanding of pelvic health, including how this affects diagnosis and treatment plans for patients.

Unconscious bias

As discussed in my previous article “How FemTech is tackling the gender health gap”, unconscious bias can affect many different areas of a patient’s health journey. Endometriosis is no different. Many women with endometriosis have felt that they were dismissed or not listened to. A survey of over 1,800 people with endometriosis found that 90% were dismissed or disbelieved by friends, family or healthcare professionals. In some experiences, this remained the case until their symptoms were “in the context of pregnancy”, as discussed by Angelina Chapin in her article about getting diagnosed with endometriosis. Moving women’s healthcare knowledge away from the ability to have a child is essential if we are to ensure that all people with a uterus receive the healthcare they require when they first need it, not solely when their health condition affects their reproductive health.

This raises the question: why is there a disconnect between the painful symptoms of people with endometriosis and how their symptoms are perceived by the wider community? One of the key reasons for this is a lack of awareness about endometriosis – one study found that only 46% of people actually know what endometriosis is.

This lack of knowledge is also seen in the medical industry. In an interview with the News Medical Life Sciences, Dr Davenport highlighted that currently “as little as 4 weeks out of 5 years of medical training may be spent on gynaecology; during that time, endometriosis may barely be mentioned.” With such lack of training about this complex condition, it is no surprise that healthcare professionals may struggle to recognise and diagnose it. Dr Annalise Weckesser suggests that, due to endometriosis being a common condition, it “warrants being part of generalist medical knowledge, rather than a condition only specialists have knowledge of.”

Physical testing

A number of physical exams and tests can be conducted by a gynaecologist to point towards a diagnosis of endometriosis. While some formations of endometriosis can be seen using imaging technology, some formations such as peritoneal endometriosis (endometrial-like tissue lining the abdominal cavity) cannot be seen with imaging technology. As a result, laparoscopic surgery is considered the gold standard for diagnosing endometriosis.

While the development of laparoscopy has revolutionised women’s health, this invasive method slows down diagnosis of endometriosis. Some patients and clinicians even delay diagnostic laparoscopic surgery on account of worries and concerns about the inherent risk of surgery in general. Speaking to Dr Frank Tu, a surgeon in the Chicago area specialising in pelvic pain, he highlighted that while the procedure is safe, “a non-invasive diagnosis method that could diagnose and stage endometriosis would help speed up diagnosis and ultimately reduce risk. This, together with the presence of symptoms, could work to help with diagnosis, staging and management of treatment”.

Is this a pipedream, or can it be made a reality?

Diagnosis breakthroughs in endometriosis

While the uncertainty around endometriosis paints a bleak picture, there are people working hard to learn what causes this disease and how this information can be used to support diagnosis and treatments. The following are some of the latest breakthroughs that have been helping to improve endometriosis diagnosis.

miRNA diagnostics

In 2016, scientists found multiple microRNA’s (miRNA) – small, single stranded noncoding RNA that regulate gene expression – that are more prevalent in people with endometriosis. The potential to use these markers in diagnosis shows great potential for improving endometriosis diagnosis and patient experiences.

While this was an exciting development, it is essential that scientific breakthroughs such as these are translated into technology that can support people with endometriosis. This is exactly what DotLab, a women’s healthcare technology company, is doing with their DotEndo diagnostic. The non-invasive blood test offers an alternative to diagnostic laparoscopic surgery, using identified miRNA to support the diagnosis of endometriosis with 90% accuracy.

Single cell analysis

Single cell analysis is a well-defined area of scientific research with large applications in oncology, whereby researchers are able to generate data from cells. One company, Hera Biotech, is working to bring this approach to endometriosis diagnosis. Through single cell analysis, the biotechnology company has been able to identify differences in the gap junctions of cells found in the endometrium for people with and without endometriosis. Gap junctions are responsible for the communication between cells, and the identification of this biomarker (which is causatively and definitively related to endometriosis) has allowed Hera Biotech to develop a definitive non-surgical diagnosis, helping to shorten time to diagnosis.

The technology requires an endometrium sample obtained during an in-office procedure using a uterine biopsy brush. This sample is then screened to allow for identification of changes in the expression profile of the cells – changes that are uniquely identified with endometriosis. Speaking to Somer Baburek, CEO of HERA Biotech, she highlighted the importance of solid science underpinning development, stating that “to start making a difference for people with endometriosis we need tools to be based on science, whether that be diagnosis, therapies or procedures.”

Technologies such as this that provide diagnosis and staging of endometriosis at an earlier stage could offer significant benefits for both patients and clinicians, as well as at a reduced cost compared to current surgical diagnosis.

Multi-diagnosis and menstrual effluent testing

With so many uterine diseases being comorbidities and having overlapping symptoms, navigating through a diagnosis can often be a process of elimination. This lengthy process is tiring for the patient and results in a delay in care. As Dr Frank Tu highlights, a “non-invasive test that can diagnose many different uterine disorders with one test would help support diagnosis”. This is exactly what Next Gen Jane is working to achieve. Its patented tampon technology allows for the collection of valuable data that is then used to diagnose and predict uterine diseases. The potential for this technology to improve patient experiences is amazing and promises a significant step forward for the improvement of women’s health.

Diagnostics companies are also realising that menstrual effluent shows great potential to support in a non-invasive diagnostic test for endometriosis. In 2018, a study was released detailing findings of reduced uterine natural killer cells in patients with endometriosis, relative to the control group. Uterine natural killer cells are an important part of the immune response to kill malignant and infected cells, with research also showing that these cells play an important role in endometrial decidualisation. Beginning in the second half of the cycle, decidualisation is the process that changes the cells forming the endometrium to prepare for the potential implantation of the fertilised egg, and then shedding of the lining.

This breakthrough in understanding the potential differences in ME between people with and without endometriosis shows potential to provide a non-invasive diagnosis. The ROSE (Research OutSmart Endometriosis) study is actively working in this space and has developed a first-of-its-kind ME sponge that can be worn externally on top of a pad.

In an area where women’s pain is so regularly considered psychological, providing a diagnosis and reason for these symptoms can support women and show that the medical industry cares about understanding their bodies, their experiences and working to find a solution.

“Having a diagnosis made the whole difference for me, an explanation as to why my periods were so heavy and so painful, so it wasn’t like I was failing as a woman.” Endometriosis patient.

The search for a treatment

Endometriosis can affect many areas of a patient’s life, including their physical and mental health as well as relationships and careers. As a result, patients are often willing to look far and wide for treatment and ways to ease the chronic pain. While there are a number of treatment options available, many people with endometriosis continue to experience chronic pain.

“You can feel isolated and alone, which is why it is important when you have endometriosis that you are getting multidisciplinary care: physical and mental.” Endometriosis patient.

“When I first got the diagnosis there were treatment options we could pursue. We have pretty much tried everything now.” Endometriosis patient.

Currently, there is no cure for endometriosis, with most treatment options aiming to slow down the growth of the endometrial-like tissue and easing symptoms. The combination oral contraceptive pill is a hormone treatment to help manage endometriosis, by thinning endometrial tissue and making periods shorter and lighter. The Mirena coil is an alternative hormone treatment, releasing progestogen-like substance over a period of five years, that reduces inflammation and therefore can reduce endometriosis symptoms. While for some patients a combination of hormonal treatments and painkillers can manage their condition, for many the symptoms of endometriosis remain a constant in their life.

“The doctor attempted to treat it with birth control and when that didn’t stop the pain; she said it was time for laparoscopy.” Endometriosis patient.

Reading stories and listening to people with endometriosis, pain stands out as the most prevalent life-impacting symptom. Laparoscopic surgery is focused on people whose pain is felt to be moderate to severe. It has been found to be effective at helping to treat the pain experienced due to endometriosis, with one study finding that six-months after surgery patients had a significant decrease in their pain. In recent years the increased use of robot-assisted surgery for endometriosis has also shown potential for improved patient outcomes when removing endometriosis tissue. Despite the potential benefits for patients and clinicians alike, more randomised control trials are needed to support the use of robotics for endometriosis and justify the higher initial costs of their implementation.

Unfortunately, if the endometrial lesions are not completely removed, they will grow back and the symptoms will return. While robot-assisted surgery is theorised to allow for greater removal of the diseased tissues, imaging and identifying endometriosis remains an issue. As a result, there are investigations as to how imaging can be improved during surgery to support surgeons in the removal of these lesions. A 2022 study investigated using new-infrared fluorescence imaging to improve the identification of endometriosis during surgery. Unfortunately, with only 61% of lesions containing endometriosis, it added little value.

“I have lesions on places that they cannot operate on, so I just manage the pain. Although the surgeries and recovery were nerve-wracking and I have hesitation about them, it was a positive experience in terms of the outcome.” Endometriosis patient.

After years of being dismissed by medical professionals, many women highlight the relief when they finally find a doctor who will listen and how this helps them through their journey from diagnosis to understanding treatment options. This in turn helps to build relationships of trust between the patient and clinician, with one patient highlighting how her “good relationship with her gynaecologist helps treatment.”

“All it took to change my life was for my doctor to show me empathy, and I wish more healthcare providers did the same.” Endometriosis patient.

Breakthroughs in potential treatments

Much like diagnosis, developing treatment options is reliant on scientific discovery about the disease and then implementation within medical devices and therapies. In addition to the more prevalent miRNAs found in patients with endometriosis, scientists have found two miRNAs with significantly lower levels in patients with endometriosis, miR – 3613 – 5p and Let -7b. As a result, scientists have researched increasing Let – 7b in patients to improve endometriosis. Testing in mice has found that increasing Let-7b reduces oestrogen signalling and lesion size, suggesting promise for an endometriosis treatment.

Other areas of women’s health show great potential for effective, minimally invasive treatment for women’s health issues. One great example of this is Ablatus, a company developing Luna, an enhanced ablation technology to treat fibroids for more women with better outcomes and experience. Its technology involves a flexible probe allowing for incisionless access to larger fibroids, as well as using bimodal electric tissue ablation to reduce the potential for damaging surrounding health tissue. As stated by CEO Dr Chung Looi, the company’s ethos focuses around “understanding patients and their needs and experiences to help develop an improved ablation technology that is more inclusive to millions of women globally”. The company’s patient-centric approach is a great example of how patient and clinician insights can be brought together with novel technology to improve treatments of women’s health issues. The potential for technology, like that of Ablatus, to provide minimally invasive, effective treatments for uterine-related conditions like fibroids and endometriosis is a great step towards improving patient journeys and quality of life.

Hope for the future

While the stories and journeys of people with endometriosis are often shrouded in pain and frustration, many people share their hope that things will be better in the future for people with endometriosis.

Tackling the challenges to improve the understanding of endometriosis and the care that patients receive requires stakeholders from all areas of the medical industry to challenge the status quo, understand their bias and perceptions of women’s health, and crucially, to listen to patients and women.

“We have to be hopeful that FemTech can cut through barriers and provide diagnostics and treatments.” Endometriosis patient.

Improving women’s health relies on the voices of women to be at the centre of the conversation, including scientific discovery and medical device development. Without understanding patients’ preferences and needs, it is impossible to create valuable solutions that will offer the best support and user experience. The medical device industry must work with clinicians and researchers to translate scientific and technical developments with patient voices to deliver innovative reliable device solutions that support women in the way they need.

“If it takes ten years, let’s start now.” Endometriosis patient.