Lena Nguyen, Class of 2021
Endometriosis is a disease that affects up to 1 in 10 women and occurs when endometrial tissue, a tissue normally found inside the uterus, grows outside of it (Bulletti et. al 2010). Over half of women with endometriosis experience dysmenorrhea, or painful menstruation, and the condition is a common factor in infertile women. Other symptoms include chronic pelvic pain and pain during intercourse. In addition to symptoms, endometriosis is associated with a higher risk of ovarian cancer and cardiovascular conditions (Shafrir et. al 2018). Despite the prevalence and severe consequences, the disease often goes unnoticed or even ignored by medical professionals (Culley et. al 2013). Women experience an average delay of 3.7 years to 5.7 years from seeking help to a diagnosis, in large part due to women being told their pain is normal or trivial and being refused referrals for medical testing. In addition, doctors are unequipped to help women with endometriosis because they lack awareness and knowledge of the disease. Endometriosis has no cure and has a high recurrence rate, meaning surgical removal of the misplaced tissue is generally not enough. Therefore, most treatments focus on alleviating symptoms.
There are no definitive causes for endometriosis, and there needs to be more research done to test the current popular theories. One common theory is that endometriosis comes from retrograde menstruation, which is when menstrual blood flows back into the fallopian tubes (Hickey et. al 2020). However, considering the high rate of retrograde menstruation, it is likely not the only factor in endometriosis. Different theories suggest that cells outside the uterus randomly become endometrial tissue or that endometrial cells travel outside the uterus through the bloodstream, though the exact mechanisms of these have yet to be studied. From genetic research, endometriosis is shown to have heritable aspects, but it is not directly inherited.
So far, proper diagnosis requires an invasive operation to see the endometrial tissue, but many researchers are looking for potential biomarkers as a better diagnostic tool. Biomarkers can be anything present in the body so long as it is measurable and found at abnormal levels in patients with the condition. In the case of endometriosis, these studies for biomarkers can be challenging because not everyone with endometriosis experiences the same symptoms if they experience any at all. In these cases, all participants would have to be surgically tested to be certain if they have the disease or not. In addition, patients have varying degrees of symptoms that can overlap with other conditions such as irritable bowel syndrome. One study did find a distinct difference between endometriosis patients and healthy patients. They found that an abundance of a protein called CD200 decreases the ability of macrophages, a type of white blood cell, to degrade cells outside their natural environment (Weng et. al 2020). A separate study looked at the ratio of two molecules called soluble VCAM-I and soluble ICAM-I that are involved in cell adhesion as a potential biomarker (Kuessel et. al 2017). The study showed that the ratio could be used to identify endometriosis with 86.7% specificity, the rate of getting a positive diagnosis correct, and 90.3% sensitivity, the rate of getting a negative diagnosis correct. Unlike the previous study, this one took into account women with varying symptoms, menstrual cycles, and misplaced tissue size and found that their results still hold.
Other recent research looks to potential cures for endometriosis by restricting the spread of misplaced tissue directly. One study considered a treatment to reduce endometrial tissue attachment to the abdominal cavity lining by investigating hyaluronan, a compound associated with the binding of tissue to the abdominal cavity. The researchers inhibited the production of hyaluronan with a different compound known as 4-methylumbelliferone, or 4-MU, and discovered that blocking the production of hyaluronan reduced attachment and invasion by endometrial cells (McLaughlin et. al 2020). Another study considered myricetin, a compound used to treat other gynecological diseases. In a series of tests with mice, the researchers found that myricetin induced cell death in the misplaced tissue and decreased the volume of the tissue over a week-and-a-half time period (Park et. al 2020). There is a long way to go before these tests can be conducted on human patients, but studies on mammals are exciting steps towards more relevant research.
Endometriosis is a common and debilitating condition, and people with the condition often have lower quality of life as well as chronic pain. There is a severe lack of knowledge on the disease by researchers and doctors, leading to many women left untreated and unheard. At the very least, the recent research on endometriosis diagnosis and cures is promising. As public awareness of endometriosis grows, so too will the number of patients whose lives improve as a result.
References
Bulletti C., Coccia M.E., Battistoni S., Borini A. Endometriosis and Infertility. Journal of Assisted Reproduction and Genetics. 2010;27:441-447
Shafrir A. L., Farland L. V., Shah D. K., Harris H. R., Kvaskoff M., Zondervan K., Missmer S. A. Risk for and consequences of endometriosis: A critical epidemiologic review. Best Practice & Research Clinical Obstetrics & Gynaecology. 2018;51:1-15
Culley L., Law C., Hudson N., Denny E., Mitchell H., Baumgarten M., Raine-Fenning N. The social and psychological impact of endometriosis on women's lives: a critical narrative review. Human Reproduction Update. 2013;19(6):625-639
Hickey M., Ballard K., Farquhar C. Endometriosis. British Medical Journal. 2020;368:m622
Weng L., Hou S., Lei S., Peng H., Li M., Zhao D. Estrogen-regulated CD200 inhibits macrophage phagocytosis in endometriosis. Journal of Reproductive Immunology. 2020;138
Kuessel L., Wenzl R., Proestling K., Balendran S., Pateisky P., Yotova 1st, Yerlikaya G., Streubel B., Husslein H. Soluble VCAM-1/soluble ICAM-1 ratio is a promising biomarker for diagnosing endometriosis. Human Reproduction. 2017;32(4):770-779
McLaughlin J. E., Santos M. T., Binkley P. A., Sultana M., Tekmal R. R., Schenken R. S., Knudtson J. F. Inhibition of Hyaluronic Acid Synthesis Decreases Endometrial Cell Attachment, Migration, and Invasion. Reproductive Sciences. 2020;https://doi.org/10.1007/s43032-019-00100-w
Park S., Song G. T., Lim W. Myricetin inhibits endometriosis growth through cyclin E1 down-regulation in vitro and in vivo. The Journal of Nutritional Biochemistry. 2020;https://doi.org/10.1016/j.jnutbio.2019.108328
Image Source: Thierry Falise [Internet]. Flickr; cited 2020 Feb 17. Available from: https://www.flickr.com/photos/iloasiapacific/8055935073
Cited:
1.https://link.springer.com/article/10.1007%2Fs10815-010-9436-1 (2010)
2.https://academic.oup.com/humupd/article/19/6/625/839568#14541279 (2013)
3.https://www.sciencedirect.com/science/article/abs/pii/S0165037820300115?via%3Dihub (2020, also: pretty sure they meant over-expressed instead of ever-expressed in the highlights)
4.doi: 10.1093/humrep/dex028
5.https://link.springer.com/article/10.1007%2Fs43032-019-00100-w
6. https://doi.org/10.1016/j.jnutbio.2019.108328
7.Shafrir, A. L., Farland, L. V., Shah, D. K., Harris, H. R., Kvaskoff, M., Zondervan, K., & Missmer, S. A. (2018). Risk for and consequences of endometriosis: A critical epidemiologic review. Best Practice & Research Clinical Obstetrics & Gynaecology. doi:10.1016/j.bpobgyn.2018.06.001
8.https://www.bmj.com/content/348/bmj.g1752
There are no definitive causes for endometriosis, and there needs to be more research done to test the current popular theories. One common theory is that endometriosis comes from retrograde menstruation, which is when menstrual blood flows back into the fallopian tubes (Hickey et. al 2020). However, considering the high rate of retrograde menstruation, it is likely not the only factor in endometriosis. Different theories suggest that cells outside the uterus randomly become endometrial tissue or that endometrial cells travel outside the uterus through the bloodstream, though the exact mechanisms of these have yet to be studied. From genetic research, endometriosis is shown to have heritable aspects, but it is not directly inherited.
So far, proper diagnosis requires an invasive operation to see the endometrial tissue, but many researchers are looking for potential biomarkers as a better diagnostic tool. Biomarkers can be anything present in the body so long as it is measurable and found at abnormal levels in patients with the condition. In the case of endometriosis, these studies for biomarkers can be challenging because not everyone with endometriosis experiences the same symptoms if they experience any at all. In these cases, all participants would have to be surgically tested to be certain if they have the disease or not. In addition, patients have varying degrees of symptoms that can overlap with other conditions such as irritable bowel syndrome. One study did find a distinct difference between endometriosis patients and healthy patients. They found that an abundance of a protein called CD200 decreases the ability of macrophages, a type of white blood cell, to degrade cells outside their natural environment (Weng et. al 2020). A separate study looked at the ratio of two molecules called soluble VCAM-I and soluble ICAM-I that are involved in cell adhesion as a potential biomarker (Kuessel et. al 2017). The study showed that the ratio could be used to identify endometriosis with 86.7% specificity, the rate of getting a positive diagnosis correct, and 90.3% sensitivity, the rate of getting a negative diagnosis correct. Unlike the previous study, this one took into account women with varying symptoms, menstrual cycles, and misplaced tissue size and found that their results still hold.
Other recent research looks to potential cures for endometriosis by restricting the spread of misplaced tissue directly. One study considered a treatment to reduce endometrial tissue attachment to the abdominal cavity lining by investigating hyaluronan, a compound associated with the binding of tissue to the abdominal cavity. The researchers inhibited the production of hyaluronan with a different compound known as 4-methylumbelliferone, or 4-MU, and discovered that blocking the production of hyaluronan reduced attachment and invasion by endometrial cells (McLaughlin et. al 2020). Another study considered myricetin, a compound used to treat other gynecological diseases. In a series of tests with mice, the researchers found that myricetin induced cell death in the misplaced tissue and decreased the volume of the tissue over a week-and-a-half time period (Park et. al 2020). There is a long way to go before these tests can be conducted on human patients, but studies on mammals are exciting steps towards more relevant research.
Endometriosis is a common and debilitating condition, and people with the condition often have lower quality of life as well as chronic pain. There is a severe lack of knowledge on the disease by researchers and doctors, leading to many women left untreated and unheard. At the very least, the recent research on endometriosis diagnosis and cures is promising. As public awareness of endometriosis grows, so too will the number of patients whose lives improve as a result.
References
Bulletti C., Coccia M.E., Battistoni S., Borini A. Endometriosis and Infertility. Journal of Assisted Reproduction and Genetics. 2010;27:441-447
Shafrir A. L., Farland L. V., Shah D. K., Harris H. R., Kvaskoff M., Zondervan K., Missmer S. A. Risk for and consequences of endometriosis: A critical epidemiologic review. Best Practice & Research Clinical Obstetrics & Gynaecology. 2018;51:1-15
Culley L., Law C., Hudson N., Denny E., Mitchell H., Baumgarten M., Raine-Fenning N. The social and psychological impact of endometriosis on women's lives: a critical narrative review. Human Reproduction Update. 2013;19(6):625-639
Hickey M., Ballard K., Farquhar C. Endometriosis. British Medical Journal. 2020;368:m622
Weng L., Hou S., Lei S., Peng H., Li M., Zhao D. Estrogen-regulated CD200 inhibits macrophage phagocytosis in endometriosis. Journal of Reproductive Immunology. 2020;138
Kuessel L., Wenzl R., Proestling K., Balendran S., Pateisky P., Yotova 1st, Yerlikaya G., Streubel B., Husslein H. Soluble VCAM-1/soluble ICAM-1 ratio is a promising biomarker for diagnosing endometriosis. Human Reproduction. 2017;32(4):770-779
McLaughlin J. E., Santos M. T., Binkley P. A., Sultana M., Tekmal R. R., Schenken R. S., Knudtson J. F. Inhibition of Hyaluronic Acid Synthesis Decreases Endometrial Cell Attachment, Migration, and Invasion. Reproductive Sciences. 2020;https://doi.org/10.1007/s43032-019-00100-w
Park S., Song G. T., Lim W. Myricetin inhibits endometriosis growth through cyclin E1 down-regulation in vitro and in vivo. The Journal of Nutritional Biochemistry. 2020;https://doi.org/10.1016/j.jnutbio.2019.108328
Image Source: Thierry Falise [Internet]. Flickr; cited 2020 Feb 17. Available from: https://www.flickr.com/photos/iloasiapacific/8055935073
Cited:
1.https://link.springer.com/article/10.1007%2Fs10815-010-9436-1 (2010)
2.https://academic.oup.com/humupd/article/19/6/625/839568#14541279 (2013)
3.https://www.sciencedirect.com/science/article/abs/pii/S0165037820300115?via%3Dihub (2020, also: pretty sure they meant over-expressed instead of ever-expressed in the highlights)
4.doi: 10.1093/humrep/dex028
5.https://link.springer.com/article/10.1007%2Fs43032-019-00100-w
6. https://doi.org/10.1016/j.jnutbio.2019.108328
7.Shafrir, A. L., Farland, L. V., Shah, D. K., Harris, H. R., Kvaskoff, M., Zondervan, K., & Missmer, S. A. (2018). Risk for and consequences of endometriosis: A critical epidemiologic review. Best Practice & Research Clinical Obstetrics & Gynaecology. doi:10.1016/j.bpobgyn.2018.06.001
8.https://www.bmj.com/content/348/bmj.g1752
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