Tag: endometriosis

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Endometriosis cellular mapping could aid diagnosis, treatment

Endometriosis cellular mapping could aid diagnosis, treatment

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Researchers have analyzed almost 400,000 cells in order to build a detailed profile of endometriosis. Image credit: Westend61/Getty Images.
  • Endometriosis affects roughly 10{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of people who menstruate.
  • In endometriosis, tissue similar to the uterine lining grows elsewhere in the body, causing painful, heavy periods, abdominal and pelvic pain, and a range of other symptoms.
  • More research is needed for this condition for which there is still no cure, diagnosis can take many years, and treatments are often ineffective.
  • New research analyzing almost 400,000 cells has revealed a detailed molecular profile of endometriosis, which may help improve diagnostic and therapeutic options for people with the condition.

Endometriosis is “a systemic disease that is often painful and chronic.” According to the World Health Organization (WHO), it affects around 190 million people — some 10{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of people who menstruate worldwide.

People with the condition experience debilitating symptoms, due to the growth of tissue similar to the uterine lining, or endometrium, elsewhere in the body.

Symptoms may include:

  • heavy and painful periods
  • spotting between periods
  • pain during sexual intercourse or when emptying the bladder or bowels
  • abdominal, lower back, and pelvic pain
  • infertility.

Currently, there is no cure for endometriosis, but symptoms can be treated with medications, such as nonsteroidal anti-inflammatories (NSAIDs), birth control pills, hormonal IUD, surgery, or a combination of these treatments.

Dr. Steven Vasilev, board-certified integrative gynecologic oncologist and medical director of integrative gynecologic oncology at Providence Saint John’s Health Center and Professor at Saint John’s Cancer Institute in Santa Monica, CA, explained the issues to Medical News Today:

“Endometriosis diagnosis and treatment today remains surgical, based on removing or destroying endometriotic lesions growing on the peritoneum (internal skin-like lining of the body) and ovaries, combined with various hormonal modulations. There has not been a major clinical advance in endometriosis diagnosis and treatment outside these relatively narrow parameters in decades.”

Now, a new study led by researchers from Cedars-Sinai Medical Center in Los Angeles, CA, published in Nature Genetics, has analyzed almost 400,000 cells to generate cellular and molecular profiles of endometrial cells.

Its findings may lead to easier diagnosis and more effective treatments for endometriosis.

Although endometriosis affects 10{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of people who menstruate, there is a lack of research into the condition. To date, there has been little cellular data about endometriosis.

This, says Dr. Kate Lawrenson, research scientist, co-senior and corresponding author of the study, and associate professor of obstetrics and gynecology and biomedical sciences at Cedars-Sinai, iswhy they undertook this research:

“Endometriosis has a devastating effect on so many people, and is remarkably common. Unfortunately, it is also one of the most underfunded diseases there is, and many basic questions remain unanswered — which is why this research provides a huge leap forward in understanding the biology of his disease.”

“I hope that work like ours can help bring conversations about endometriosis into the forefront, to improve awareness and also increase much-needed funding for endometriosis research,” she told MNT.

In this new study, the researchers used state-of-the-art methods to analyze more than 370,000 cells from 21 participants, 17 of whom had endometriosis and four who did not.

They sampled different tissues — peritoneal endometriosis, ovarian endometriomas, eutopic endometrium samples, and uninvolved ovary tissues. Eutopic endometrium and uninvolved ovary tissues came from people with and without endometriosis.

“The methodology of the study is basic molecular biology. It has done something I have not seen in other endometriosis studies, which is [to] try and break down the various characteristics of endometriosis-type cells depending on [the] body location of the lesion. It is cataloging the cell type and surrounding microenvironment,” Dr. G. Thomas Ruiz, OB/GYN lead at MemorialCare Orange Coast Medical Center in Fountain Valley, CA, not involved in this study, explained for MNT.

The researchers analyzed the cells using droplet-based single-cell RNA sequencing. This method identifies which genes are transcribed to make RNA, determining which proteins the cell makes.

By identifying which genes are transcribed, researchers can see differences between the types of cells under investigation.

Using this method, the researchers identified molecular differences between the major subtypes of endometriosis, including peritoneal endometriosis and ovarian endometrioma.

Dr. Lawrenson explained their findings: “We saw a number of differences when we compared endometriosis cells to endometrium. The endometriosis cells are responding differently to hormones and communicate differently with the immune system.”

“The fact that they are behaving so differently is really exciting, as it potentially provides us with new opportunities for therapeutic targeting,” she added.

“This atlas of molecular findings will help researchers move the ball forward towards achieving earlier diagnosis, differentiation between subtypes of endometriosis, a better understanding of the overlap with ovarian cancer in a small but significant percentage of endometriosis patients, and insights into eventual development of molecularly targeted therapy for endometriosis,” said Dr. Vasilev.

So could this research lead the way to new diagnosis and treatment methods? Dr. Lawrenson believes so, and is investigating potential diagnostics for the condition:

“We urgently need a blood test for endometriosis and this is now one of our top research priorities in the laboratory. We were encouraged to see that in endometriosis, multiple cell types overproduce the same genes, which should make it easier to detect those genes in the blood.”

The research discovered that endometriosis cells and normal cells respond differently to the immune system. New therapies that target the immune system might prove effective in treating the condition, as Dr. Lawrenson explained.

“Recent advances suggest that we might be able to treat endometriosis by correcting how the immune system responds to lesions. This is particularly exciting because there might be immune therapies used for other diseases that could be rapidly repurposed for the treatment of endometriosis,” she told MNT.

There is still a need for further research, and Dr. Ruiz suggested directions this research might take: “Endometrioma, superficial versus deep infiltrating had very specific cellular characteristics. The next step would be in vitro studies to see if various endometriosis cell types act differently to current hormone treatments.”

With the mapping of endometriosis, this research has highlighted potential diagnostic and treatment pathways for investigation — it can only be good news for the many people with this debilitating condition.

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Women with endometriosis may face higher risk of stroke

Women with endometriosis may face higher risk of stroke

  • A new, big possible analyze analyzed information of 112,056 ladies more than 28 many years.
  • Making use of styles to regulate for opportunity confounding factors, the review concluded that ladies with endometriosis experienced a 34{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} larger chance of stroke.
  • Scientists cautioned that though the correlation involving endometriosis and stroke is vital to take note, the absolute chance for any unique in their lifetime for stroke stays reduced.

Women of all ages with endometriosis may perhaps facial area a increased risk of stroke, according to a substantial, future analyze revealed in Stroke, a journal of the American Stroke Affiliation, which is a division of the American Coronary heart Affiliation.

About 10{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of women of all ages of reproductive age are acknowledged to have endometriosis, which is a chronic and often unpleasant ailment where tissue comparable to the tissue that lines the uterus grows outside the house that organ.

Previously investigate, which includes this 2016 research, has uncovered endometriosis to be affiliated with an amplified risk of coronary coronary heart disease.

“Prior investigate from our staff noticed an affiliation involving endometriosis and enhanced possibility of hypertension, substantial cholesterol, and myocardial infarction,” Leslie Farland, Sc.D., initial writer of the study and assistant professor of epidemiology and biostatistics at the University of Arizona in Tucson, stated in an email to Professional medical Information Currently.

“Given that these situations are affiliated with stroke risk, we preferred to recognize if women of all ages with endometriosis also experienced an elevated danger of stroke,” Prof. Farland said.

The scientists made their analyze to defeat limits uncovered in other scientific tests hunting at endometriosis and the threat of stroke, which provided next up with participants about brief durations and limited accounting for likely confounding factors.

For their analyze, the scientists appeared at members of the Nurses’ Health and fitness Examine II (NHSII): 116,429 women of all ages who have been nurses involving the ages of 25 and 42 in 1989. Contributors in the NHSII have been mailed questionnaires each individual two decades via 2017 that questioned thoughts about diseases and danger factors.

Next, researchers excluded NHSII participants who had a record of stroke, myocardial infarction, most cancers (other than nonmelanoma pores and skin cancer) or a coronary artery bypass grafting just before June of 1989 or who had an endometriosis diagnosis that was not confirmed by laparoscope. That left 112,056 members, with 5,244 of these acquiring endometriosis. Between the chosen individuals, there were 893 incidents of strokes about 28 yrs of adhere to-up.

The researchers made use of models altered for achievable chance components such as the participants’ liquor intake, menstrual cycle pattern in adolescence and bodily activity. Moreover, researchers deemed no matter if the possibility of stroke could be affected by other variables this kind of as higher blood force, having a hysterectomy and postmenopausal hormone remedy.

Researchers identified females with a background of endometriosis experienced a 34{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} higher chance of stroke than females without having a background of endometriosis in styles adjusted for likely confounding aspects.

“This is crucial to be aware but not an extremely high greater chance,” cautioned Stacey Missmer, Sc.D., one more creator of the review and a professor of obstetrics, gynecology and reproductive biology at the Michigan Condition University Faculty of Human Drugs, informed MNT. “Also, the absolute chance for any specific in their life span for stroke nevertheless stays very small.”

Researchers located the association between endometriosis and increased chance of stroke to be partially mediated by occurrences of hysterectomies (the removing of the uterus) or oophorectomies (removing of the ovaries).

“We have been capable to compute that about 40{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of it could be … brought on by the large prevalence of hysterectomy, with and with no oophorectomy, but that suggests that there’s an supplemental 60{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} that … just can’t be attributed to that, that will have to have other elements in perform,” Prof. Missmer stated.

The association was also partially mediated by postmenopausal hormone remedy, beginning menopause at 45 years old or earlier as perfectly as getting a record of hypertension or substantial cholesterol. No substantial dissimilarities were seen in the connection involving endometriosis and stroke throughout many aspects which include age, system mass index or historical past of infertility.

For this research, most contributors (93{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809}) had been white women of all ages. Nonetheless, Prof. Farland explained to MNT that “we would hope the results of our examine to be generalizable to other racial and ethnic teams.”

Dr. Ken Sinervo, health-related director for the Centre for Endometriosis Treatment in Atlanta instructed MNT that endometriosis is far too usually “poorly managed by hysterectomy, which may possibly be pointless in many scenarios.”

“The outcome is an elevated hazard of cardiovascular conditions, which could in any other case be largely averted with appropriate use of Laparoscopic Excision,” Dr. Sinervo wrote, referring to the process the place a surgeon helps make tiny incisions in the patient’s reduce abdomen. Through those people, surgeons will insert a camera to look for endometriosis lesions which they take out working with a laparoscope.

Prof. Missmer stated she hopes this analyze will increase awareness between wellbeing practitioners and endometriosis people about the threats of hysterectomies.

“As this evidence builds of a partnership between that specific surgery and other lifelong, increased possibility elements, ladies need to be far more knowledgeable that there can be these other impacts of owning people surgical procedures and the clinicians who treatment for them require to also be conscious of that as perfectly,” she discussed.

Moreover, Prof. Missmer stressed that it is critical for wellbeing practitioners and endometriosis people to be cognizant that endometriosis can effect a woman’s cardiovascular and cerebrovascular wellness.

“It implies that main treatment medical professionals, not just gynecologists want to be … monitoring and having to pay awareness to all of the symptoms and chance things of a client with endometriosis,” she added.

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The problem with endometriosis research

The problem with endometriosis research

Women’s reproductive health attracts far less research funding than almost all other medical research. As for endometriosis — a condition that affects around 10{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of women of reproductive age — the lack of research is particularly striking. This debilitating condition can impact day-to-day life, education, work, and mental health, but its cause remains unclear, and there is no cure for it. Why is it so underresearched?

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Why is endometriosis still so underresearched? Image credit: Michele Pevide/Getty Images.

“That time of the month,” “shark week,” “crimson tide,” “got the painters in,” “on the blob,” “visit from Aunt Flo,” “the curse” — these are just a few of the many euphemisms for something experienced by 50{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of the female adult population: menstruation. But why are there so many? Are we afraid to call it by its name?

Could it be that society’s reluctance to speak plainly about periods is one of the reasons why issues with women’s reproductive health are so underrecognized and underresearched?

Most females start to menstruate between the ages of 9 and 15. Monthly cycles continue until the menopause, which, on average, happens at around 52 years of age. So most women will have in the region of 450 periods during their life.

For around 20{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of women, these are merely a monthly inconvenience. But for more than 80{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809}, they are accompanied by some measure of pain. And for 1 in 4 women, the pain can be severe enough to impact daily life.

We often normalize period pain as “part of being a woman.” For many, mild to moderate pain associated with menstruation can be controlled with over-the-counter pain relief, diet, and exercise.

However, debilitating pain is another matter. Menstrual Matters, a nonprofit online information hub, states that period pain “should not be regularly severe and debilitating.”

If it is, there is likely to be an underlying cause, which may need medical investigation. For pain that persists, occurs in the run-up to periods, and does not respond to pain relief, that cause may be endometriosis.

Endometriosis is “a systemic disease that is often painful and chronic.” Current estimates suggest it affects 176 million reproductive-age women worldwide.

Symptoms can include:

  • debilitating pain during menstruation
  • excessive bleeding during periods
  • pelvic pain at other times of the month
  • lower back pain
  • pain when emptying the bladder or bowels
  • pain during and after sexual intercourse

In severe cases, endometriosis can cause fertility issues. Some 40{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of women with infertility also have endometriosis.

The condition is characterized by the growth of tissue similar to the endometrium, or womb lining, in areas outside the uterus. This tissue — endometrial lesions — commonly grows in the following areas, though it can also infiltrate other parts of the body, such as the:

  • ovaries
  • fallopian tubes
  • ureters
  • bowels and bladder
  • abdominal wall

In line with the menstrual cycle, the lesions grow and bleed, forming scar tissue. This bleeding, inflammation, and scarring cause the characteristic pain of endometriosis.

A major issue with endometriosis is getting a diagnosis.

A 2019 review in the American Journal of Obstetrics and Gynecology (AJOG) explained why this might be:

“Despite its high prevalence and cost, endometriosis remains underfunded and underresearched, greatly limiting our understanding of the disease and slowing much-needed innovation in diagnostic and treatment options.”

Researchers acknowledge that endometriosis presents complex diagnostic challenges. Because the symptoms vary so much, the condition is often misdiagnosed as bowel and digestive disorders.

One 2020 United States study recorded that 75.2{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of patients reported being misdiagnosed with another physical health (95.1{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809}), a mental health problem (49.5{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809}), or both before they received an endometriosis diagnosis.

This study reported that misdiagnosis with a mental health problem was more common in those with younger age of endometriosis symptom onset.

The difficulty often leads to long delays between first reporting symptoms and a diagnosis of endometriosis. On average, women wait some 8.5 years for endometriosis to be confirmed, with some waiting much longer.

Doctors go through several stages to diagnose the condition, starting with palpating the abdomen to feel for lesions. They may use transvaginal ultrasound and MRI scans, but these do not always show lesions.

Healthcare professionals can only make a firm diagnosis of endometriosis by laparoscopy. This is a surgical process done under general anesthesia where a camera is inserted through a small incision in the abdomen to view the pelvic organs.

A 2021 focus group study in the Netherlands identified several issues with diagnosing endometriosis:

  • Most women do not feel their symptoms are taken seriously.
  • Many women believe their experiences of menstruation are normal, often because of what they are told by their mothers, so they do not seek treatment.
  • Medical professionals find it hard to differentiate between “normal” menstrual complaints and signs or symptoms suggestive of endometriosis.

Initially, most women are offered nonsteroidal anti-inflammatory drugs such as ibuprofen. However, little research has been done into whether these alleviate the severe pain caused by endometriosis, and anecdotal evidence suggests they have little effect.

As endometriosis is estrogen-dependent, medications that inhibit estrogen can be effective in controlling pain and inhibiting the growth of lesions. These include oral birth control pills and shots (Depo-Provera). However, some women experience side effects from these, such as headaches, irregular bleeding, and weight gain.

Gonadotropin-releasing hormone treatments offer an alternative. By suppressing reproductive hormones, they also restrict the growth of lesions. The side effect of suppressing these hormones is menopausal symptoms, such as hot flashes, tiredness, sleep issues, vaginal dryness, and joint pain. However, people can take low dose hormone replacement therapy to alleviate these.

For severe pain, or when other treatments have proven ineffective, surgery will be considered. Laparoscopy, as well as being used for diagnosis, is also used to remove endometrial lesions.

Most people gain short-term pain relief after the removal of lesions, and for some, the effect is long lasting. However, according to the American College of Obstetricians and Gynaecologists, up to 80{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of women see their pain return within 2 years.

As a last resort, hysterectomy — removal of the uterus — may be considered, but evidence for its benefits in treating endometriosis is inconclusive. It is a major irreversible procedure, and a woman who has a hysterectomy will no longer have periods or become pregnant.

In the U.S., endometriosis is diagnosed in approximately 1 in 10 women of reproductive age — diabetes is diagnosed in around 10{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of the U.S. population, both male and female.

In 2020, the U.S. government announced that funding for endometriosis research would be doubled to $26 million annually. In the same year, the National Institutes of Health (NIH) reported research spending on diabetes of $1,156 million.

Why the discrepancy? A 2021 study into gender disparity in research funding found that the “NIH applies a disproportionate share of its resources to diseases that affect primarily men, at the expense of those that affect primarily women.”

The authors went further, stating that diseases affecting primarily or solely men tended to be overfunded, whereas those affecting mostly or only women were underfunded.

And the pattern is repeated in the United Kingdom, where a 2018 analysis by the U.K. Clinical Research Collaboration found that only 2.1{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of publicly funded medical research went to reproductive health and childbirth.

According to Emma Cox, Chief Executive of Endometriosis UK, the National Institute for Health Research has funded more than 8,000 projects since its inception in 2006, only 11 of which address endometriosis.

“Women’s health, including endometriosis, has historically attracted far less research funding than other areas. We think this is because of a mixture of taboo and ignorance — whatever the reason, we are determined to put it right.”

– Emma Cox, Endometriosis UK

Lack of funding is not the only problem. Endometriosis is a complex condition. The symptoms vary so much between women that doctors used to think it was more than one condition. Therefore, it can be hard for researchers to know where to begin.

Some research has been done on animal models, but there are obstacles. Since primates are the most similar to people, they would be the best animals for modeling endometriosis. However, there are many objections to their use.

To avoid this problem, a team led by Prof. Philippa Saunders, chair of reproductive steroids at the University of Edinburgh, is developing a mouse model to study endometriosis. “The lowest species in which we can really do something meaningful is the mouse. That’s why the mouse is such an important model in reproductive research,” she says.

The researchers are studying the early development of the disease, with the aim of finding indicators of endometriosis in the blood. They hope this might provide a way of identifying the disease early before damage occurs.

However, Prof. Saunders is frustrated by the lack of funding for endometriosis research: “This progress was only possible because of increased pressure from patient groups who have been much more vocal over the last few years, working with clinical professionals to lobby funders.”

According to the 2019 review of endometriosis research in AJOG, “[c]omprehensive and interdisciplinary approaches to disease management and increased education and disease awareness for patients, healthcare providers, and the public are needed to remove stigma, increase timely and accurate diagnosis and treatment, and allow for new advancements.”

Emma Cox is one of many calling for more action:

“We would like government and other funders to address the historic underfunding of endometriosis research in order to identify the cause of the condition, work towards a cure, and develop better treatments. Developing better treatments is vital given that endometriosis can be a chronic and debilitating condition and current treatment options don’t work for everyone.”

As recently as 2020, the UK’s All-Party Parliamentary Group (APPG) on Endometriosis report highlighted that the cause of the condition was still unclear.

“Historically, with limited investment in research into women’s health in general, there’s been so little investment in research into endometriosis that we don’t even know what causes it, and without knowing the cause, a cure cannot be found,” it says.

The APPG called for “[c]ommitment for vital investment in research into the cause of endometriosis, treatment and management options, and diagnosis,” adding that:

“Without investment in research, this condition will rob the next generation of women [of] the education, care, and support they deserve.”

Lobbying groups and charities in both the U.K. and U.S. are working hard to raise awareness of endometriosis. But what is really needed is government commitments to fund more research.

Whether these will be forthcoming remains to be seen.