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New therapeutic targets for endometriosis could be on the horizon

Microscopic photo of endometrium showing brown staining in many of the tissue’s stromal cells, along with blue glands essentially devoid of brown staining. The brown pigment indicates the presence of BDNF (brain-derived neurotrophic factor), a potent growth factor protein that stimulates nerves to proliferate and migrate through the tissue, increasing the transmission of pain. 

UB study reveals how neurotrophins and their receptors could be novel therapeutic targets for pelvic pain in endometriosis

By Ellen Goldbaum

Release Date: August 9, 2023

BUFFALO, N.Y. – New research on the connection between endometrial lesions and pain in endometriosis could lead to new therapies for this chronic, painful and poorly understood condition that affects 5-10% of women worldwide and costs an estimated $69 billion in medical and surgical expenses. Endometriosis is a condition where tissue similar to uterine tissue develops and grows outside of the uterus, causing chronic pain that can be severe.

Published online in May in the American Journal of Pathology and featured on the cover of the journal this month, the work was led by researchers in the Department of Obstetrics and Gynecology in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, in collaboration with researchers at the University of Michigan.

Robert N. Taylor, MD, PhD, senior author on the paper and professor of obstetrics and gynecology and pathology and anatomical sciences in the Jacobs School, describes the drawbacks of current endometriosis treatments.

“Laparoscopic surgical removal of endometriosis lesions remains a primary mode of treatment, but it can be expensive, with attendant risks of complications, and often is associated with recurrence,” he says. “Hormonal medications have been useful but their long-term use is associated with menopausal symptoms and side effects.”

The new research focuses on the potential connection between the presence of nerves in endometriosis lesions and pain. “The association of pain with endometriosis has been known for a hundred years,” Taylor says, “but the relationship between the volume of lesions and the degree of pain symptoms is poorly correlated.”

To determine how lesions and pain are related, the UB researchers teamed up with researchers at the University of Michigan, who Taylor says are experts in the brain’s perception of pain and central sensitization or nociplastic pain, which is a quality of pain that does not arise from an identifiable injury or lesion.

The UB team of scientists has studied the biology of the uterus and endometriosis lesions for decades and now focuses on how nerves present in those tissues are peripheral generators of pelvic pain.

Only in the past 20 years has it been established that the density of nerves in endometriosis lesions and the endometrium (the inner lining of the uterus) is higher in women with endometriosis.

“This led us to propose that this phenomenon might be explained by the excessive expression of neurotrophins, proteins that stimulate the growth and migration of neurons,” Taylor says. “This paper addresses the molecular pathways that are activated in endometriosis and offer new targets for therapy.”

Using established neural biomarkers isolated from endometrial tissue biopsies obtained from eight adult women (four patients with endometriosis and four without), the researchers were looking to identify biochemical mediators of endometriosis-associated pelvic pain. They used immunofluorescence histochemistry, a technique that visualizes parts of a cell with fluorescently labeled antibodies, to confirm that neurons are present in human endometrial tissue. Endometrial stromal cells isolated from the issue expressed neurotrophins and their receptors.

The researchers propose that IL-1β, a potent inflammatory protein, activates a membrane receptor in endometrial stromal cells, predominantly through the c-Jun N-terminal kinase (JNK) pathway, to promote neurotrophin and neurotrophin receptor production and signaling. That increase, in turn, activates the development of new neurons in the brain, which can potentially create a vicious cycle of inflammation and perceived pelvic pain.

The researchers also found that tropomyosin receptor kinase A/B expression, one of the main neurotrophin receptors in endometrium, was almost twice as high in cells from patients with endometriosis than in those from control subjects, an increase that also is mediated through the JNK pathway.

“We therefore postulate that clinical trials using JNK inhibitors have the potential to reduce neuroinflammation in women with endometriosis,” says Taylor.

“It is our hope that by identifying and correlating peripheral and central generators of pain, we can come up with new pharmacological approaches for treating endometriosis symptoms,” Taylor says. 

“Targeted therapies of the future have the promise of blocking nerve growth and pain transmission, ideally without compromising endocrine function,” he says. “This is the ultimate goal of our research.”

UB co-authors include Sarah L. Berga, MD, chair of the Department of Obstetrics and Gynecology in the Jacobs School and Jie Yu, research associate professor in the department. 

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• Published: 06 February 2024

Surge in endometriosis research after decades of underfunding could herald new era for women’s health

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Advances in organoids and the role of the microbiome and diet are leading to new diagnostics and treatments for endometriosis, motivating a precision health approach to this long-neglected disease.

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Rahmioglu, N. et al. Nat. Genet. 55 , 423–436 (2023).

Article   CAS   PubMed   PubMed Central   Google Scholar  

Fonseca, M. A. S. et al. Nat. Genet. 55 , 255–267 (2023).

Article   CAS   PubMed   Google Scholar  

Shin, S. et al. J. Pathol. 261 , 323–334 (2023).

Wang, Y. et al. Front. Immunol. 14 , 1133672 (2023).

Horne, A. W. et al. Lancet 396 , 909–917 (2020).

Masuda, H. et al. Reprod. Biomed. Online 43 , 3–13 (2021).

Cousins, F. L. et al. J. Obstet. Gynaecol. Res. 49 , 1090–1105 (2023).

Article   ADS   PubMed   Google Scholar  

Orr, N. L. et al. J. Path. Clin. Res. 9 , 302–312 (2023).

Article   Google Scholar  

Filby, C. E. et al. J. Pers. Med. 11 , 1314 (2021).

Article   PubMed   PubMed Central   Google Scholar  

Muraoka, A. et al. Sci. Transl. Med. 15 , eadd1531 (2023).

Chadchan, S. B. et al. Cell Death Discov. 9 , 28 (2023).

Lucarini, E. et al. Pain 163 , 861–877 (2022).

Nishimoto-Kakiuchi, A. et al. Sci. Transl. Med. 15 , eabq5858 (2023).

Bendifallah, S. et al. NEJM Evid. 2 , 7 (2023).

Viganò, P. et al. J. Endometr. Uterine Disord. 2 , 100031 (2023).

Bendifallah, S. et al. J. Clin. Med. 11 , 612 (2022).

Scheck, S. M. et al. Aust. N. Z. J. Obstet. Gynaecol. https://doi.org/10.1111/ajo.13765 (2023).

Article   PubMed   Google Scholar  

Marečková, M. et al. Preprint at bioRxiv https://doi.org/10.1101/2023.11.03.564728 (2023).

Gnecco, J. S. et al. Med. 4 , 554–579.e9 (2023).

Zondervan, K. T. et al. Nat. Rev. Dis. Primers 4 , 9 (2018).

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The Endometriosis Foundation of America Announces Formation of Scientific and Medical Board

“The Endometriosis Foundation of America has worked for over ten years to fund landmark endometriosis research and push the medical and scientific communities to focus on this disease that impacts so many, but continues to be largely ignored. Our newly announced Scientific Advisory Board brings together some of the greatest minds in the world to guide our scientific strategy into our next decade as a foundation and thus work to improve the lives of 200 million women living with endometriosis.” said Tamer Seckin, MD, co-founder of EndoFound.

NEW YORK (November 11, 2021) –  The  Endometriosis Foundation of America (EndoFound) , the leading non-profit for endometriosis, today announced the formation of their Scientific and Medical Board with 26 international charter members serving an initial three-year term with no term limits. Chairing the committee is Dr. Dan Martin, Scientific & Medical Director at EndoFound. EndoFound co-founder Tamer Seckin, MD will also sit on the Board.

The Board will help guide the scientific strategy of EndoFound including its scientific research.  Specifically, they will help define the grants objectives, review grant applications, review medical and scientific material for the website and other communications, as well as review the revamped EndoEducation program to be rolled out at schools across the country.

“The Endometriosis Foundation of America has worked for over ten years to fund landmark endometriosis research and push the medical and scientific communities to focus on this disease that impacts so many, but continues to be largely ignored. Our newly announced Scientific Advisory Board brings together some of the greatest minds in the world to guide our scientific strategy into our next decade as a foundation and thus work to improve the lives of 200 million women living with endometriosis.” said Tamer Seckin, MD, co-founder of EndoFound.

“I am proud to Chair the Scientific Advisory Board for the Endometriosis Foundation of America. Our ultimate mission at EndoFound is funding research to develop new diagnostic tools and treatments, and ultimately find a cure for endometriosis. This group of celebrated experts will work with us to bring more awareness and education to the masses about this disease to help achieve our goal”, added Dan Martin, MD, Chair of the EndoFound Scientific Advisory Board and EndoFound Scientific and Medical Director

Charter members of the Endometriosis Foundation of America’s Scientific and Medical Board: 

• Ayse Ayhan, MD PhD - Consultant Pathologist, Hamamatsu & Hiroshima University School of Medicine & Seirei Mikatahara Hospital, Japan
• Piraye Beim, PhD  - Founder and CEO, Celmatix, USA
• SerdarBulun, MD  - John J. Sciarra Professor of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, USA
• Katie Burns, PhD  - Assistant Professor of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, USA
• Noemie Elhadad, PhD - Associate Professor of Biomedical Informatics, Columbia University Department of Biomedical Informatics, USA
• Asgi Fazleabas, PhD  - University Distinguished Professor and Associate Chair of Research, Michigan State University Department of Obstetrics, Gynecology and Reproductive Biology, USA
• Caroline Gargett, MD - NHMRC Leadership Fellow, Theme Leader, Women's Health, The Ritchie Centre; Head, Endometrial Stem Cell Biology Laboratory, Hudson Institute of Medical Research; Postgraduate Co-ordinator, Department of Obstetrics and Gynaecology, Monash University, Australia
• Victor Gomel, MD  - Professor Emeritus in the Department of Obstetrics and Gynecology, University of British Columbia, Canada
• Peter Gregersen, MD - Professor, Institute of Molecular Medicine, Feinstein Institutes for Medical Research; Professor, Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, USA
• Linda Griffith, PhD -  Director, Center for Gynepathology Research; Member, Center for Environmental Health Sciences; Member, Center for Emergent Behaviors of Integrate Cellular Systems; Member, Koch Institute for Integrative Cancer Research, USA
• Sun-Wei Guo, PhD  - Professor, Fudan University, Shanghai College of Medicine, Department of Biochemistry and Molecular Biology,            China
• Keith Isaacson, MD  - Director of Minimally Invasive Gynecologic Surgery and Infertility, Newton Wellesley Hospital; Associate Professor of Obstetrics and Gynecology, Harvard School of Medicine, USA
• Pinar Kodaman, MD, PhD  - Associate Professor of Clinical Obstetrics, Gynecology & Reproductive Sciences; Director, Advanced Endoscopic Reproductive Surgery Program; Director, Reproductive Endocrinology and Infertility Elective, USA
• Philippe Koninckx, MD, PhD  - Professor of Obstetrics and Gynecology, Gruppo Italo Belga, Research Director, Latifa Hospital, Italy / Belgium
• Mario  Malzoni, MD  - Director of the National Center for Endometriosis (Malzoni Group); Chief of the Center for Advanced Pelvic Surgery; Honorary-Professor Emeritus at the University and Research Centre in Moscow (RUSSIA); Scientific Director of the Malzoni Group, Italy
• Dan Martin, MD  - Scientific & Medical Director, EndoFound, USA
• Liselotte Mettler, MD, PhD - Emeritus Professor, University Clinics of Schleswig-Holstein, Consultant, German Medical Center (GMC), Germany
• Christine Metz, PhD  - Professor, Institute of Molecular Medicine, Feinstein Institutes for Medical Research; Associate Dean, Elmezzi Graduate School of Molecular Medicine; Professor, Departments of Obstetrics & Gynecology and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell; Director, Faculty Affairs, Feinstein Institutes for Medical Research, USA
• Resad Pasic, MD, PhD  - Professor of Obstetrics and Gynecology and Director of the Fellowship in Minimally Invasive Gynecologic Surgery; University of Louisville Department of Obstetrics and Gynecology and Women’s Health, USA
• Marc Possover, MD, PhD  - Director at Possover International Medical Center; Prof. of Neuropelveology at Univ. of Aarhus; Associate Prof. at Univ. of Cologne; Honorary and Founding President at International Society of Neuropelveology, Switzerland
• Harry Reich, MD  - Honorary Medical Director Emeritus and Senior Medical Advisor to EndoFound, USA
• Tamer Seckin, MD  - President and Founder, EndoFound; Director, Seckin Endometriosis Center; Clinical Associate Professor, Zucker School of Medicine at Hofstra Northwell, USA
• Ie-Ming Shih, MD, PhD  - Richard W. TeLinde Distinguished Professor; Johns Hopkins Medicine Department of Gynecology and Obstetrics, USA
• Hugh Taylor, MD -  Anita O'Keeffe Young Professor of Obstetrics, Gynecology, and Reproductive Sciences and Professor of Molecular, Cellular, and Developmental Biology; Chair of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine; Chief of Obstetrics and Gynecology, Yale-New Haven Hospital, USA
• Robert N. Taylor, MD, PhD  - Professor of Obstetrics and Gynecology and Assistant Dean, University at Buffalo, Department of Obstetrics and Gynecology, Jacobs School of Medicine & Biomedical Sciences, USA
• Arnaud Wattiez, MD  - Head of GYN Department at Latifa Hospital; Head of Gynecological Endoscopy Courses at IRCAD; Professor of Obstetrics and Gynecology at University of Strasbourg, UAE 

Endometriosis Foundation of America

EndoFound is the country’s largest non-profit 501(c)(3) organization dedicated to increasing disease recognition, providing advocacy, facilitating expert surgical training, and funding landmark research for endometriosis. Engaged in a robust campaign to inform both the medical community and the public, EndoFound places particular emphasis on the critical importance of early diagnosis and effective intervention while simultaneously providing education to medical professionals and their patients. To learn more or get involved go to www.endofound.org/ .

EndoFound Media Contacts:

Lauren Peteroy Kelly, Scenario PR

Jeanne Rebillard, EndoFound  [email protected]

Copyright endonews.com © 2024. All Rights Reserved - by Domino Media - Sitemap - Author Login

All rights are reserved. Is is not allowed to copy any information or picture without given permission. Legal Information: The information in endoNews.com - treatment, statistics and education is specially prepared for non professional public. Although this site contains up to date materials, actuality of the information or links are not guarantied the site management has not responsible by law. You should not diagnose or treat yourself depending on these information. By searching on this spesific web site you are automaticaly accepting these legal rules. 1809

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A Debilitating Illness, Often Ignored

Nearly one in 10 women experiences the chronic pain of endometriosis, but for many the symptoms are dismissed. Why is this still happening?

By Dani Blum

Sarah Digby barely remembers her first period, but the third is locked in her brain. She was in a seventh-grade reading class in San Antonio, her feet propped up on the desk chair in front of her, when the pain shot down from her pelvis to the back of her legs. Her feet went numb. She worried she wouldn’t be able to move. She tried to breathe slowly, to stop herself from panicking, while the pain that would define the next decade of her life set in.

As she grew up, Ms. Digby thought she just had “a weird body.” She bled through pads, underwear, sheets. She woke herself up one night, screaming from the pain. “I thought: It must be my fault — I must not know how to control my period the way everyone else does,” she said. In her early 20s, the pain became so intense that she collapsed on the subway and in the shower. She once passed out on a plane, and the last thing she remembered was buzzing for a flight attendant as they prepared to close the cabin door.

It wasn’t until Ms. Digby was almost 27, nearly 15 years after she started menstruating, that she was diagnosed with endometriosis, a chronic condition that affects 10 percent of women and girls, according to the World Health Organization . But the broad range of symptoms and a lack of awareness about how to recognize and treat the disease can prevent patients from getting help. There is no cure for endometriosis, but doctors and researchers are uncovering tools to manage the often debilitating pain that comes with the disease. Without an accurate diagnosis, though, patients like Ms. Digby are left grasping for answers.

When Ms. Digby did seek medical attention, she was told that she might have ovarian cysts, that she might have a sexually transmitted infection and that her intrauterine device had led to pelvic inflammation. She felt “medically gaslit,” she said, until she stumbled across an article about endometriosis and sought out a center in New York, where she lives, specifically designed to treat it.

“We all know the symptoms of a heart attack,” Ms. Digby, 32, said. “Why don’t we know the symptoms of an extremely common disease?”

Why does endometriosis cause so much pain?

Endometriosis comes with a tangled knot of symptoms, many of which are characterized by extreme pain. Painful sex. Painful urination and bowel movements. Menstrual cramps that cause stabbing pain and aches in the abdomen and lower back. Gastrointestinal disruptions, like painful diarrhea and constipation, which patients often confuse for signs of another health issue.

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‘Women Suffer in Silence': New Study Finds Way to Diagnose Endometriosis Without Surgery

A new study conducted by a team of new york researchers has discovered a way to diagnose endometriosis without invasive surgery., by linda gaudino • published march 29, 2022 • updated on march 29, 2022 at 3:43 pm.

"Drug seekers" and "pill poppers" are some phrases that have been used to describe women seeking medical help from the suffering brought on by a chronic condition often mistakenly chalked up to "period pain." One study found a new way to diagnose endometriosis without the agony and costs of invasive surgery.

Endometriosis is an inflammatory condition when tissue that normally lines the uterus grows outside onto other organs. Over 11% of women between the ages of 15 to 44 may have this disorder, according to the Office on Women's Health .

Patients can experience a variety of symptoms, such as menstrual cramps, pain during sex, digestive problems, spotting, and infertility. The cause is unknown but could be linked to genetic factors or immune system disorders.

24/7 New York news stream: Watch NBC 4 free wherever you are

"Initially, painful periods, not normal -- that's a stigma that still exists that women are just going to suffer. No, pain is not ever normal, so let's get rid of that," 36-year-old April Summerford told NBC New York.

Many times during visits to the doctor, she was told she was normal and powered through the pain. In her experience, one doctor avoided her endometriosis diagnosis simply by remembering the line, “I don’t want it to be endo because I can’t help you.”

Over 1,800 women nationwide participated in this study, including Fresno, Calif. native Summerford, who has been battling infertility and the disease since she first started her menstrual cycle as a teen.

Get Tri-state area news delivered to your inbox. Sign up for NBC New York's News Headlines newsletter.

Approximately, 30% to 50% of endometriosis patients may experience infertility, based on the American Society for Reproductive Medicine . 

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"The severity does not correlate with disease symptoms, so you can have very severe disease with very mild symptoms. And then there are some people who do not have symptoms at all, and they learn about their diagnosis in an infertility workup or even in a C-section," Dr. Christine Metz told NBC New York.

Dr. Metz is one of the lead scientists at the Feinstein Institutes for Medical Research who worked on this study. She is also the co-director of Research OutSmarts Endometriosis (ROSE), which first launched this project in 2017.

The team studied menstrual effluent as a way to non-invasively diagnose the condition and identified cells in the blood that could differentiate between healthy and sick patients.

"We really pioneered studying menstrual effluent in the setting of any condition. It was not well studied prior to us jumping in, and it was really only studied for regenerative medicine purposes because there are stem cells as the endometrium regrows every single month," said Dr. Metz.

These findings are one step further toward acquiring tolerable treatments and shortening the delay between symptoms and diagnosis.

"The only treatment that has been developed in the last 12 years is also hormone-based just like all the other treatments developed thus far, and none of them treat the disease. They treat pain," added Dr. Metz.

March marks Women's History Month and Endometriosis Awareness Month. The team is recruiting the next phase of participants. To learn more about clinical trials, click here .

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Painful Endometriosis Could Hold Clues To Tissue Regeneration, Scientist Says

Terry Gross

It's estimated that one in 10 women experience endometriosis during their reproductive years, a condition where cells that line the uterus go rogue by moving to other organs, taking root and spreading there, leading to terrible pain. Many women who have the disorder struggle to be properly diagnosed.

As Linda Griffith, a top biological engineer at MIT, relates in a recent New York Times article by Rachel Gross, it was years before she knew why she was experiencing exceptionally heavy periods and debilitating pain.

"I was told it was normal. I was told that I was under stress ... [that] I was rejecting my femininity," Griffith says now.

When a doctor finally diagnosed her with endometriosis in the late 1980s, Griffith says, "I was relieved to know that finally somebody found something wrong with me — because I knew something was wrong."

Her treatment involved hormone therapy and multiple surgeries, including a hysterectomy. Her personal experience, Griffith says, has informed her research, as she's come to see the study of the endometrium as a great way to unlock some of the mysteries of tissue regeneration.

Griffith first became famous in the science world for her work in grafting living tissue shaped like a human ear onto the back of a mouse — an achievement that's helping tissue engineers figure out the rich mix of factors needed to grow skin and cartilage for human transplant. In 2009, she co-founded the MIT Center for Gynepathology Research , where she broadened the scope of her work to include endometriosis.

"The regeneration of the endometrium is weirdly not studied as much as it should be," she says. "But it's fascinating because you get about a centimeter of growth of tissue that has beautifully formed blood vessels, an immune system, all of the structures of the tissue — over a period of about two weeks."

To understand endometriosis and find better treatments, she says, society needs to become more comfortable addressing women's reproductive health in general.

"It is not acceptable in society really to talk about your period," she says. "There's many period problems: Heavy menstrual bleeding, fibroids, all of these kinds of things. You just don't talk about your period. So that has to change."

Interview highlights

On the remarkable qualities of the cells of the endometrium, which is shed each month when a women gets her period and which then regenerates

There's very rapid cell growth. There's no scarring in a normal individual, and understanding that might help us with heart regeneration and other kinds of wound healing. ... There's also an enormous influx of different kinds of immune cells throughout the cycle we don't really understand: Are immune cells migrating in from blood? Are they proliferating in place? We know that certain kinds of immune cells in the uterus are very different than elsewhere in the body. So there's a lot of fascinating things that orchestrate this beautiful event every month going on under the direction of these hormones.

Linda Griffith received a MacArthur "Genius" Fellowship in 2006 for her work in tissue engineering. Melissa Blackall/www.melissablackall.com/National Academy of Engineering hide caption

Linda Griffith received a MacArthur "Genius" Fellowship in 2006 for her work in tissue engineering.

On what is happening in the body with endometriosis

We don't know exactly what causes it, but what we find in patients is that the lining of the uterus, the endometrium, is found growing outside the uterus. It can grow on the lining of the abdomen. It can invade the bladder, it can invade the bowel. It can land on the ovaries and cause a big cyst. When it causes symptoms and it's found growing there, we call it endometriosis.

On why endometriosis can be so painful

We don't know all of the reasons. There's a lot of speculation around why it causes so much pain. It could be because there's inflammation that comes from leaking blood every time the woman has her period. The little lesions that are growing in the abdomen also can bleed. They cause the blood vessels to become very leaky. And whenever you have an accumulation of blood, you get inflammation. This can send signals for pain.

Shots - Health News

How 'bad medicine' dismisses and misdiagnoses women's symptoms.

Think about it: When you even just get a paper cut, it hurts, right? Now imagine that you have a whole bunch of those all over the inside of your body. It's going to hurt for the same reasons and more. If you have something like a blister that goes on and you're continually irritating it, it's going to hurt. Later, when the disease progresses, you can get distortion of the internal organs. The ovary may spin out of place. This can pull on a nerve all the time. So it's like you're constantly, constantly being kicked or something, because that nerve is being pulled all the time by the distortion of the organs that comes from scar tissue that builds up and glues things together.

On the notion of "period privilege," and how it can prevent women from being diagnosed with endometriosis

Some women just don't understand that other women could have these terrible, terrible things happening, because they themselves don't experience those symptoms. "Period privilege," as I'm calling it, could be active or passive. Passive is just they don't think about it and they kind of find it hard to believe. But active — and I encountered this a lot — is women saying, "It can't be that bad." And some of these women are gynecologists, like the one who treated my niece who had endometriosis, and the gynecologist told my sister my niece was making everything up. So I think period privilege is one of those things where women who don't have menstrual problems don't believe the women who do. Either just they don't think about it, or they actively say, "Don't talk about it," because it makes women look weak.

Goats and Soda

A menstrual expert's surprising tips on how to talk about your period.

On the prevailing theories about how endometrial tissue migrates

There's potentially a lot of different ways it could happen. There are theories that during [fetal] development you have migration of cells from the neural crest and you get cells migrating all over the body to their respective ultimate positions. And sometimes [with] the cells moving along in a train, some cells fall off the train. And then when you go through puberty, the cells that fell off the train are sitting there and they can develop into the endometrium or other tissues. So that is a probable cause in some women — that they had a developmental issue.

There's also a lot of evidence that in ... people who are in their 20s or 30s, that menstrual tissue, instead of all going out the cervix as it should, it goes out the fallopian tubes. And this happens in all women. When you have women undergoing surgery during their periods, you can find menses in the abdominal cavity. So it happens in all women. But what we don't know is why in some women it may not be cleared away by the immune system as it should. There are about 10% of women who have endometriosis. So why that tissue wouldn't be cleared away, we don't exactly know. Is it something strange about their endometrium? Is their endometrium very aggressive or is it something strange about their abdominal cavity? Is the immune system weak or not proper or is it fertile ground for the endometrium?

On why she initially hid her disease from her colleagues

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I was diagnosed in 1988 and joined the faculty in 1991. ... That was at a time when the premier endocrinology textbook — I had to teach endocrinology at Harvard Medical School at the time — it had a tiny chapter, two or three pages, on endometriosis and it said: "The typical patient is a nulliparous [never given birth] white woman in her late 30s who's highly educated and has an anxious personality." The textbook said that. [In] 1991.

We call that a diagnosis bias. Because the people who would get diagnosed were the people who had resources and who would be persistent and had access to care.

We know endometriosis affects all different races, all different [societies] around the world — everybody has about the same incidence of endometriosis. So to get back to why didn't I study it? I just didn't want to think about it. At that time, you didn't talk about gynecology. You still don't talk about it if you have a gynecology disease and you're an engineering professor or any kind of science professor. So I hid. I had elaborate rituals — how I ran my life — to hide the fact that I had a gynecology disease. Nobody really knew it. You just didn't talk about it.

Amy Salit and Kayla Lattimore produced and edited the audio of this interview. Bridget Bentz, Molly Seavy-Nesper and Deborah Franklin adapted it for the Web.

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• basic research
• reproductive health
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Global study shows the experience of Endometriosis is rooted in genetics

Researchers at the University of Oxford, in collaboration with 25 teams across the world, have published the largest study to date of the genetic basis of endometriosis.

Their study included DNA from 60,600 women with endometriosis and 701,900 without. It revealed compelling evidence of a shared genetic basis for endometriosis and other types of pain seemingly unrelated to endometriosis, including migraine, back pain and multi-site pain. The study has also revealed that ovarian endometriosis has a different genetic basis from other disease manifestations. The results open up new avenues for designing new medical treatments targeting subtypes of endometriosis, or even the repurposing of existing pain treatments for endometriosis.

Endometriosis has enormous implications on the quality of a woman’s life. This severe inflammatory condition occurring in 5-10% of women of reproductive age (190 million globally) can cause constant and intense pelvic pain, fatigue, depression, anxiety, and infertility. It is characterized by the presence of tissue that resembles the uterus lining (endometrium) outside the uterus. The location of these endometriotic deposits is primarily on organs within the pelvis (e.g. ovaries, pelvic surfaces and ligaments, bowel or bladder), although more rarely it can also be found outside of the pelvis. The huge impact on the health of many women is compounded by the fact that endometriosis can only reliably be diagnosed through surgery and sometimes imaging, and often takes many years to diagnose (eight years on average from first symptoms). Treatment is limited to repeated surgeries, and hormonal treatments with many side-effects that do not allow women to get pregnant.

It is known that endometriosis can run in families, and therefore that genetic factors (heritability) play a role in how it develops in some women but not in others. Very little is known about the causes of endometriosis, and studying genetics - by comparing the DNA code in women with and without the disease - can give us clues to the biological processes that are the basis for onset and progression.

By conducting the largest genetic study ever conducted, the researchers found 42 areas across the genome that harbour variants that increase risk of endometriosis. By linking these variants to the profiles of molecules in endometrium and blood, they identified a range of genes that were differently expressed in these tissues and therefore had a likely role in disease development. This list of genes is important for further work to develop of new treatments, better targeted to subtypes of disease. For instance, they found that some genetic variants were more associated with ovarian ‘cystic’ endometriosis than superficial disease spread throughout the pelvis.

What they noted in particular is that many of the implicated genes play a role in pain perception and maintenance. Indeed, they found that there was a shared genetic basis for endometriosis and a range of other chronic pain types such migraine, back pain, and multi-site pain. This could be related to so-called sensitisation of the central nervous system, which makes individuals suffering from chronic pain more prone to other types of pain. These findings open up the possibility of designing new pain-focussed non-hormonal treatments, or repurposing existing pain treatments, for endometriosis.

Dr Nilufer Rahmioglu , Senior Research Scientist at the Wellcome Centre for Human Genetics , University of Oxford, and first author of the study commented: 'Using different datasets of women with and without endometriosis, some of which had unprecedented detailed data on surgical findings and pain experience collected using standardised criteria, allowed us to generate a treasure trove of new information about genetically driven endometriosis subtypes and pain experience.'

Professor Krina Zondervan , Co-Director of the Endometriosis CaRe Centre , and Head of the Nuffield Department of Women’s & Reproductive Health , University of Oxford, senior author on the paper, commented: 'Endometriosis is now recognised as a major health issue affecting women’s lives. This study involved the analysis of DNA from more than 60,000 women with endometriosis worldwide, in an unprecedented collaboration of 25 academic and industry groups contributing their data and time. It has provided a wealth of new knowledge on the genetics underlying endometriosis, which will help the research community in their efforts to come up with new treatments and possibly new ways of diagnosing the disease benefiting millions of women worldwide.'

The full paper, ' The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions ', is published in Nature Genetics .

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NYT article discusses endometriosis as a “key to unlocking some of biology’s greatest secrets”

Dr. Griffith at home with her husband, Doug Lauffenburger, a systems biologist at M.I.T. Credit… Ilana Panich-Linsman for The New York Times

In this cover story of  The New York Times Health Section, CGR Director Linda Griffith highlights the seriousness and prevalence of endometriosis. She discusses the important work CGR researchers are doing to understand and address this widespread disease.

RESPONSE: From the outpouring of response to the April 27, 2021 New York Times article about our endometriosis research, we learned that women with gynecology diseases and those who love them want to be heard , to learn about research and therapies, and to teach others what they learn.

We are thus happy to announce the launch this summer of a series of educational events, and provide opportunities for volunteering to help with research and awareness! Sign up to our mailing list to learn more about the life in the lab at the MIT Center for Gynepathology Research!

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Endometriosis: How new treatment 'changed my life'

Taking the dog for a walk is a routine task for most people. But Jessica Rafferty would often have to cut outings short due to crippling pain.

She, like one in 10 women, lives with endometriosis - a condition where tissue similar to the lining of the womb grows elsewhere inside the body. It can be incredibly painful, and can take years to diagnose.

And there is no known cure.

But Jessica is part of the search for effective treatments. She is among 30 women taking part in the University of Edinburgh study looking at dichloroacetate, a drug currently used to treat rare metabolic conditions in children.

It helps to control lactate levels, which have been found to be higher in patients with some cancers and endometriosis.

• Endometriosis care needs urgent improvement, MPs say
• Endometriosis: The condition that can take over seven years to diagnose

Jessica, who's 24, went to hospital about 200 times, with her symptoms initially attributed to IBS and coeliac disease. She even had her appendix removed, before endometriosis was finally discovered to be the underlying cause.

But during the 12-week trial, her symptoms dramatically improved.

"The pain decreased immensely. I was able to go and take the dog out and do six-mile walks - and do things that on a daily basis I would not do, or if I did try and do them I would be in a lot of pain.

"It's definitely changed my life so far, having been on this treatment after so many failed treatments and medications and operations."

Dichloroacetate's key benefit is that, unlike every other drug currently used to treat the condition, it is non-hormonal.

Andrew Horne, professor of gynaecology and reproductive sciences, who is leading the study, says: "Clearly endometriosis affects a young female population many of whom are wanting to try and get pregnant, so they don't want to take hormones; they don't want to take a contraceptive. So this would be a very different approach."

What is endometriosis?

• It's where tissue similar to the lining of the womb grows elsewhere inside the body - often around reproductive organs, bowel and bladder
• Like the womb lining, tissue builds up every month then bleeds
• However, unlike a period, there is no way for the blood to escape
• The build-up of trapped blood can result in internal lesions and scar tissue
• Some people experience no symptoms but for many others the pain can be debilitating, and the condition can lead to infertility
• There is currently no known cause or cure for the condition.

Prof Horne says even though it's too early for any conclusive results on how well the drug works, the findings so far are "exciting". The team is hoping to expand, and receive enough funding for a much larger trial involving up to 400 volunteers.

The work is among a number of research projects offering hope for people with the condition that will be highlighted at the World Congress on Endometriosis.

Current treatment options are limited to repeated surgeries (including full hysterectomies), hormonal drugs or painkillers such as ibuprofen or paracetomol.

Another study, by experts at the University of Oxford, is seeking to unlock the genetic secrets of the condition.

For the past three years, Prof Krina Zondervan and her team have been analysing tissue samples donated by 60,000 patients with endometriosis around the world. It's the largest study of its kind ever undertaken.

Their soon-to-be published work reveals new details about endometriosis, including confirmation that it is not one single condition. They have also uncovered genetic links to other inflammatory conditions such as asthma and osteoarthritis, and pain conditions such as migraines and back pain.

Prof Zondervan says they hope the understanding will mean they can investigate whether drugs currently used for those conditions could be repurposed to treat endometriosis: "And that will really speed up the process of drug discovery."

In simple terms, now that a link has been discovered, a drug used to treat asthma could be tweaked to treat endometriosis. That process would be a lot quicker than building a drug from scratch.

The potential breakthroughs have been welcomed by campaigners, who argue research into the condition has been chronically underfunded.

Emma Cox, CEO of Endometriosis UK, says: "Research is vital, offering hope for those with endometriosis and future generations.

"We need to know so much more to support those living with this chronic disease to manage their sometimes debilitating symptoms, and to one day find a cure".

As promising as this research might prove to be, approval for any new non-hormonal drug treatment is likely to be a few years away.

But for a community which has often felt overlooked, ignored and disbelieved, there is comfort in knowing that potential medical breakthroughs are on the horizon.

Endometriosis care 'needs urgent improvement'

Medics missed woman's endometriosis for 17 years.

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Research priorities for endometriosis differ among patients, clinicians, and researchers

Affiliations.

• 1 Columbia University Fertility Center, Columbia University Irving Medical Center, 1790 Broadway, PH, New York, NY 10019. Electronic address: [email protected].
• 2 MRC Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK.
• 3 Center for Infertility and Reproductive Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
• 4 Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, MA; Boston Center for Endometriosis, Boston Children's Hospital and Brigham & Women's Hospital, Boston, MA; Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI.
• 5 Department of Epidemiology and Biostatistics, Mel & Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ.
• PMID: 32142827
• DOI: 10.1016/j.ajog.2020.02.047

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Endometriosis: New Research, New Directions

— greater awareness of the diseases toll is spurring new research on multiple fronts.

by Diana Swift , Contributing Writer, MedPage Today Reviewed By in Hee (Jeannie) Kim, MD, FACOG, Associate Professor, Division of Gynecologic Specialty Surgery, Program Director, Fellowship in Minimally Invasive Gynecologic Surgery, Department of Obstetrics and Gynecology, Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, New York City

"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

As endometriosis maintains its stranglehold on at least 10% of those born with a uterus worldwide, researchers are hopeful that heightened awareness of this systemic inflammatory condition will lead to routine screening, earlier diagnosis, increased research funding, and novel, non-hormonal treatments.

Wanted: A New Attitude in Education

According to Serdar Bulun, MD, chair of the Department of Obstetrics and Gynecology at Northwestern University in Chicago, medical training and textbooks need to be overhauled to address the burden of this disease.

"There's still a huge disconnect in the textbooks, with the thinking being that this is just primary dysmenorrhea of adolescence and it will magically disappear when a young woman reaches her early 20s," Bulun said. "But the probability is that a female fetus is already disposed to endometriosis in utero and if endometriosis is not recognized early, it will evolve into the full debilitating syndrome."

Another misconception in current medical training is that a bit of surgery will solve the problem. "We have to understand that endometriosis is preventable and treatable, but it is something a woman will have to live with for the rest of her life," Bulun said. "You can't just resect a few pieces of tissue and it will go way. That's what surgeons told patients back in 1980, and it has continued to trickle down into the textbooks used today."

Clinical Screening

Hugh Taylor, MD, chair of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine in New Haven, Connecticut, noted that targeted, endometriosis-specific questioning by doctors about menstrual periods will hasten diagnosis and should be part of every young woman's basic clinical examination.

"You can't just ask about pain, because pain is subjective and no one knows if their pain is worse than someone else's," he explained. Pointed questions should focus objectively on disability – for example, how much school, work, and social time is actually being lost to menstrual problems?

"Traditionally, there's been a terrible 10-year delay in diagnosis, and greater awareness among the public and professionals is key," Taylor continued. "We're just starting to recognize the total systemic nature of the disease so it can be correctly diagnosed. There's enough critical mass now to make a difference."

He said he agrees that the medical curriculum needs updating, but that's easier said than done as "everyone interested in change is looking to get a piece of the curriculum pie."

Biomarkers for Noninvasive Diagnosis

Many researchers are looking at genetic markers as harbingers of endometriosis. At the Feinstein Institutes for Medical Research in Manhasset, New York, the ROSE (Research Outsmart Endometriosis) group is assessing genetic markers associated with endometriosis by characterizing and comparing tissues from affected and unaffected women in hopes that such a classification will lead to a simple diagnostic tool.

Taylor said he is optimistic that the next few years will see a quick and easy blood test providing early diagnostic clarity. His team has been researching microRNAs. "There are about 20,000 of these in the circulation. They don't get translated into proteins but you can find the signatures of many diseases in them, including endometriosis," he said.

In 2020, Taylor and his Yale colleague Valerie Flores, MD, published a study in American Journal of Obstetrics & Gynecology showing that microRNA biomarkers reliably distinguished endometriosis from other gynecologic pathologies. Such a noninvasive assay could serve many women, reduce the time to diagnosis, surgical risk, decades of discomfort and lost time, disease progression, comorbidities, and healthcare costs, Taylor explained.

His team is also investigating why some patients do not respond to progesterone therapy. "Inflammation contributes to progesterone resistance, but it is not the whole story since some endometriosis remains resistant to progesterone even when we remove the inflammation in the lab," he said. Faulty precursor stem cells in the endometrium are another avenue of inquiry, and the group is targeting stem cells in animal trials.

New Treatments

The therapeutic holy grail are medications that do not involve estrogen suppression, the current mainstay of therapy. "Estrogen deprivation works, but it also deprives other organs like the brain of the estrogen they need to function properly," and it stops ovulation in women who want to become pregnant, Taylor said.

He said he foresees next-generation treatment evolving in two broad categories: immune modulators to get the immune system to reject extrauterine endometrial tissue and targeted molecular agents of the sort used in cancer therapy.

Hormone-based therapy will likely remain at the therapeutic core for this estrogen-driven disease for the foreseeable future, Bulun said. "Endometriosis is a function of ovulation and menstruation. If a drug doesn't stop that, it won't work."

He noted that risk is greater in modern women since they are exposed to far more menstrual cycles than their ancestors – with earlier menarche, fewer pregnancies, and less ovulation-suppressing breastfeeding, and longer lifespans. "The total number or menses over a woman's lifetime has increased 10-fold. But this is not a normal process from an evolutionary perspective. You don't need to have so many uninterrupted cycles," he said.

Bulun said he hopes the pharmaceutical industry can come up with strategies for interrupting ovulation/menses with minimal side effects and no impact on ovarian reserve. "The best we can do with current technology is decrease the severity of ovulation, so we need new options."

In the meantime, newer hormone-based treatments that block follicle-stimulating hormone and luteinizing hormone help decrease inflammation and pain, noted Adi Katz, MD, of Lenox Hill Hospital in New York City. "There are also several new studies looking at pain treatment with nerve-stimulating electrodes."

Alternatives to Surgery

Some women will always require the removal of unresponsive endometriotic adhesions, and minimally invasive nonsurgical procedures to do this are under investigation. Borrowing a page from the oncologist's handbook, a recent study adapted an experimental therapy called nanoparticle-mediated magnetic hyperthermia, which is used to remove cancerous tissue. The magnetic particles target vascular endothelial growth factor receptor 2, which abounds in endometriotic tissue. Delivered intravenously and targeted locally, the particles generate heat when exposed to an alternating magnetic field. At temperatures above 46°C, the endometriotic tissue dies within 20 minutes. This method appears to be safe and well-tolerated in humans and animals.

Curbing the Inflammatory Response

Controlling the systemic inflammation and associated pain of established endometriosis is another treatment goal. "Medication that goes beyond symptom management to disease treatment will likely be done with immunotherapy," Katz said.

Some researchers are homing in on a possible causative role for macrophages in endometriotic pain. For example, a U.K. team found that levels of the hormone insulin-like growth factor (IGF)-1 in pelvic cavity tissue from women with endometriosis were higher than in unaffected women and aligned with the severity of their pain scores. In cell culture experiments, the group showed that adding IGF-1 from macrophages promoted nerve cell growth and activation, and in mice with endometriosis blocking the cell receptor for IGF-1 reversed their previously observed pain behavior. Therefore, distinguishing potentially harmful macrophages from healthy ones may lead to targeted molecular treatments for pain.

A review by a Chinese team highlighted several therapeutic agents currently under investigation for application in endometriosis, including:

• Pentoxifylline, a methylxanthine with anti-inflammatory properties that acts as a phosphodiesterase inhibitor, has been proposed for treating endometriosis. This drug has long been used for cerebrovascular and peripheral vascular diseases, as well as other conditions involving defective microcirculation
• N-palmitoylethanolamine, a structural analog of anandamide, has anti-inflammatory, immunosuppressive, analgesic, neuroprotective, and antioxidant effects. It inhibits mast cell activation, blocking the crosstalk between mast cells and nociceptive nerve fibers peripherally. It downregulates microglial cell behaviors and thus reduces associated central pain hypersensitization and has successfully reduced pain due to chronic lumbosciatalgia
• Anti-angiogenic drugs used in cancer treatment to inhibit the growth of tumor-supporting blood vessels are another type under scrutiny for possible use in endometriosis. In addition, natural antioxidants such as grape-sourced resveratrol and immune-modulating biologics such as the tumor necrosis factor inhibitors used to treat psoriasis, rheumatoid arthritis, and Crohn's disease may mitigate endometriotic inflammation as well

Preliminary lab and mouse studies by a team that included Taylor and Flores found that the Janus kinase inhibitor tofacitinib (Xeljanz) reduced the burden of endometriotic lesions and might well prove effective in humans.

Rebalancing the Microbiota

Mounting evidence suggests that, as in other painful chronic diseases, the microbiota is important for proper immune function. A dysbiotic gut, and disruptions in other microbial milieus such as that of the reproductive tract, may foster the development of endometriosis, chronic pelvic pain, and subfertility.

The microbiome appears to affect estrogen regulation as modulated by the estrobolome, as well as inflammation and other endometriosis-promoting mechanisms within the genital tract.

This ecosystem also plays a role in the gut-brain axis, which mediates pain. One future option may be to manipulate colonies of bacterial, fungal, and viral microorganisms to increase strains associated with good immune function and the absence of endometriosis and reduce those linked to harmful immune-disturbing strains.

The microbiota of affected women does appear to differ. A study of human and animal microbiota found that bacteria were enriched and more diverse in endometriosis patients, although there was no consensus on which specific microbiota compositions were associated with the disease.

However, vaginosis-associated bacteria and Lactobacillus depletion in the cervicovaginal microbiome were associated with endometriosis and infertility in the majority of studies. Moreover, animal studies supported a bidirectional relationship between the gut microbiota and endometriosis onset and progression.

In other chronic pain conditions such as inflammatory bowel disease (IBD), exposure to antibiotics, artificial sweeteners, and chemical food additives have all been considered as possible contributors to immune dysfunction and the rising prevalence of IBD. A question is whether these dietary and other environmental exposures could also be immune-impacting culprits in endometriosis?

Reducing Environmental Exposures

Investigators such as Anna Pollack, PhD, MPH, of George Mason University College of Health and Human Services in Fairfax, Virginia, are seeking to clarify the possible role of different endocrine-disrupting chemicals involved in endometriosis in order to inform policies for reducing exposure and risk. Her group is comparing tissue samples from eutopic endometrium with those from ectopic endometrium, measuring for a range of chemical exposures to evaluate the dose of these chemicals in target tissue.

"Per- and polyfluorinated substances – or PFAS – are ubiquitous in many consumer products, and we found they were also ubiquitous in eutopic endometrial tissue," Pollack said. "While there was no evidence that PFAS in endometrial tissue were associated with the development of endometriosis, several were associated with the risk of more severe disease -- that is, American Society of Reproductive Medicine stages 3 or 4 versus stages 1 or 2." The next step may be to investigate if PFAS may be linked to disease subtype such as [superficial] endometriosis versus deep-infiltrating disease or endometriomas.

Other investigators are focusing specifically on diethyl hexyl phthalate, a chemical that commonly occurs in insecticides, cosmetics, and food packaging and is present in high levels in endometriosis patients.

Research Funding on the Rise

Endometriosis research has long suffered from underfunding , but that is starting to change. In 2020 Congress voted to double to $26 million the existing funding for endometriosis, which in 2019 was only $13 million, which equated to less than $1 per year for each diagnosed U.S. patient.

Increasing recognition among members of the public and the medical profession is a first essential step. "The biggest obstacle we face is still lack of awareness of this common condition," Taylor said. "About two-thirds of patients will respond to a simple birth control pill, and if we can catch endometriosis early before it evolves into the full syndrome, we can help a lot of women."

Katz is optimistic that there may even eventually be a cure for endometriosis: "If we can understand the disease process, if we can identify what causes endometriosis to grow and implant, and how the immune system responds, we can successfully block the development of endometriosis," she said.

Read the previous installments of this series:

Part 1: Endometriosis: Understanding the Pathogenesis and Pathophysiology

Part 2: Diagnosing Endometriosis

Part 3: Managing Endometriosis: Research and Recommendations

Part 4: Case Study: Endometriosis or Hernia?

Part 5: Endometriosis: Fertility and Pregnancy

Part 6: The Latest on What to Know About Managing Endometriomas

Part 7: Enhancing the Doctor-Patient Dialogue About Endometriosis

Part 8: Case Study Mystery: Swollen, Painful Belly Button During Menstruation

Part 9: Endometriosis: Why Is Research Funding So Low?

Part 10: Endometriosis's Links to Inflammatory Conditions and Other Diseases

Part 11: Endometriosis: Mitigating Risk, Progression, and Severity

Diana Swift is a freelance medical journalist based in Toronto.

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