Some women look forward to their period week and the easing of premenstrual symptoms, while other women aren't quite as enthusiastic. But for women with endometriosis, the arrival of their period can cause normal daily activities like work and school to grind to a halt due to extreme and debilitating pain and, in some cases, heavy blood loss. Sufferers of this chronic condition can also experience other symptoms such as fatigue, bowel and bladder problems, along with infertility. Approximately one in ten women of reproductive age are estimated to be affected by endometriosis, with the prevalence being as high as 30-50% in women with infertility.
So, what exactly is endometriosis?
Each month cells in the lining of the uterus (endometrium) are built up to prepare for a potential pregnancy. If conception does not occur, the cells break down and leave the body as a period. In endometriosis, endometrial-like cells found elsewhere in the body act in this way, building up and then breaking down. This process in the wrong location results in inflammation and the formation of endometriosis lesions.
What causes endometriosis?
“While the exact cause of endometriosis is not known, there are many theories proposed to describe its pathogenesis,” Christine Metz, PhD, Professor, the Feinstein Institutes for Medical Research at Northwell Health tells Technology Networks. “One hypothesis is the events that occur in utero, such as the displacement of tissue that would normally develop into the uterus to sites outside of the uterus during embryo development. Another theory is the events that occur just after birth (such as endometrial bleeding caused by the withdrawal of mom’s hormones); and events that occur in adulthood (such as retrograde menstruation or the backflow of menstrual effluent into the pelvic cavity, where it can seed and develop into lesions). The theory of retrograde menstruation is the most commonly accepted theory. However, none of these theories have been proven.”
The role of genetics
Genetics are also thought to play an important role in endometriosis. “The female children of women with endometriosis have a six-fold increase in developing the condition compared to children of women without endometriosis,” Metz explains.
She goes on to tell us that: “Recent genome-wide association studies (GWAS) involving women with endometriosis and healthy controls revealed 27 loci or gene regions associated with the disease. However, the genetic underpinnings of endometriosis are quite complex and fine-mapping of each one of these regions is needed before we truly understand the role of genetics in endometriosis. These studies will likely reveal that this condition has numerous subtypes.”
Why is it taking so long to diagnose patients?
Despite an increasing understanding of the disease, endometriosis is notoriously difficult to diagnose, with studies suggesting that women on average wait over seven years for a diagnosis.
As Margaret DeFranco, Senior Research Nurse at the Feinstein Institutes for Medical Research at Northwell Health tells us, “There are many reasons why women with endometriosis experience delays in diagnosis. First, the symptoms of endometriosis are relatively vague and non-specific – including bloating and other gastrointestinal symptoms that encourage women to visit GI physicians (who do not typically diagnose/treat patients with endometriosis). Second, many teens and women are asymptomatic – many of these women end up being diagnosed later when confronted with infertility. Third, many teens and women opt to delay diagnosis or refuse it all together because definitive diagnosis requires invasive laparoscopic surgery. Many teens and women who find relief from their symptoms following treatment with oral contraceptives and/or hormone therapies may stop pursuing a definitive diagnosis. And finally, there is a pervasive dismissal of women’s complaints about pelvic pain (which has been described in the literature). Some young teens are told by their mothers/sisters/aunts/grandmothers – who may themselves have had endometriosis – that their symptoms that prevent them from attending school, athletic events and social activities are normal – so they do not seek help.”
Added to this, endometriosis research is severely underfunded, with only $6 million allocated for the disease in 2020
Moving towards a non-invasive diagnostic
DeFranco and Metz are part of The ROSE (Researchers OutSmart Endometriosis) study team, which since 2016 has been working hard to develop better ways to diagnose and treat the condition. Instead of relying on invasive laparoscopy procedures, the team are aiming to diagnose women with endometriosis through the analysis of menstrual effluent (blood). “Through our research, we have identified a significant difference in cells derived from menstrual effluent, the stromal cells that are very aggressive in patients with endometriosis. By identifying those cellular differences, we hope to develop an FDA approved non-invasive diagnostic test,” DeFranco tells us.
As part of the work, the team has already developed a first-of-its-kind menstrual effluent collection sponge, which offers an easier and more comfortable method of sample collection for the women taking part in the study. Unlike traditional methods such as menstrual cups or tampons, the sponge can be worn externally, on top of a pad.
At present, the ROSE study is enrolling women with symptoms of endometriosis who are likely to undergo diagnostic laparoscopic surgery soon. By comparing these patients’ menstrual effluent results with the laparoscopic surgery (the gold standard), the ROSE team will be able to prove that their method can diagnose endometriosis or predict which women should undergo diagnostic laparoscopic surgery. “These results are a crucial component of our multi-year FDA approval process for the menstrual effluent-based diagnostic,” Metz tells us.
Increasing our understanding of endometriosis
In addition to developing an improved method of diagnosing endometriosis, the ROSE study team is also working to increase our understanding of the genetic basis of the disease and relate it to what is occurring at the cellular level.
By studying the differences in menstrual effluent of women with endometriosis compared to women without endometriosis, the team hopes to be able to understand the disease better and develop more effective treatments.
A window into the uterus
It seems as though menstrual effluent has the potential to be a useful tool or biospecimen to study and screen for other uterine health issues such as uterine fibroids, uterine cancer and infertility. However, this doesn’t seem to be the case yet. “Believe it or not, menstrual effluent has not been well-studied. Based on our findings, we consider menstrual effluent to be a rich, easily attained sample and an effective window into the uterus,” DeFranco tells us. “We hope our findings will spark future studies of menstrual effluent that will lead to significant improvements in women’s health.”
Christine Metz and Margaret DeFranco were speaking with Anna MacDonald, Science Writer, Technology Networks.