Executive Summary
Endometriosis is a common health problem for women. An estimated 11% of U.S. women have the gynecologic disorder, which happens when the lining of the uterus grows outside of the uterus.
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In women with endometriosis, when the endometrial tissue enters the abdominal cavity, it attaches to organs in the abdominal and pelvic cavities, such as the ovaries, the intestines, or other organs or tissues. This tissue continues to follow the monthly menstrual cycle, and the resulting bleeding can cause inflammation, scarring, and pain.
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Researchers have identified patterns of genetic activity that may be used to diagnose endometriosis and its severity, which possibly offers an alternative to diagnostic surgery through a simple noninvasive procedure.
Endometriosis is a common health problem for women. An estimated 11% of U.S. women have the gynecologic disorder, which happens when the lining of the uterus grows outside of the uterus.1 In women with endometriosis, when the endometrial tissue enters the abdominal cavity, it attaches to organs in the abdominal and pelvic cavities, such as the ovaries, the intestines, or other organs or tissues. This tissue continues to follow the monthly menstrual cycle, and the resulting bleeding can cause inflammation, scarring, and pain. It is prevalent in 38% of infertile women and in 71-87% of women with chronic pelvic pain.2
Currently, laparoscopy is the only definitive way to diagnose and stage endometriosis that occurs on the pelvic lining and organs. However, the time lag can be more than a decade from symptom onset to diagnosis, which emphasizes the need for a less invasive, more cost-effective approach.
Researchers at the University of California San Francisco (UCSF) have identified patterns of genetic activity that may be used to diagnose endometriosis and its severity, which possibly offers an alternative to diagnostic surgery through a simple noninvasive procedure.3 The prototype diagnostic method not only distinguishes endometriosis from other disorders of the uterus, but it also can identify the severity of the disease.
This type of molecular diagnostic approach would not have been possible without advances in genomics and bioinformatics, said Linda Giudice, MD, PhD, distinguished professor and chair of obstetrics, gynecology, and reproductive sciences at UCSF in a release accompanying the publication. “Importantly, there are relatively few genes in each ‘classifier’ of disease or of no disease and endometriosis stage that have the potential for non-surgical diagnostic development,” said Giudice, who served as senior author of the paper. “The approach also could be used to detect disease recurrence without requiring surgery, and the newly identified gene profiles and pathways resulting from this approach have opened doors for innovative targeted therapy development for endometriosis-related pain and infertility.”
Review the results
To perform the study, researchers used samples from the National Institutes of Health (NIH)/UCSF Human Endometrial Tissue and DNA Bank established by Giudice. Scientists used DNA microarray technology to identify which genes were involved in making protein in each woman’s endometrial tissue. They looked at 148 samples:
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77 samples came from women with endometriosis.
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37 samples came from women without endometriosis but with other uterine/pelvic problems.
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34 samples came from women without any uterine conditions.
The investigators used machine learning, a computer-based technology, to analyze the gene activity of endometrium tissue samples. Machine learning allows computers to learn from an activity without explicit programming. Scientists then examine the interactions caused by the information on large numbers of genes being translated into proteins through a process called gene expression.
Not only could investigators in the study determine which samples came from endometriosis patients and those who did not have endometriosis, but they also could tell the difference between samples from endometriosis patients and those from patients with other uterine disorders. The new testing also allowed scientists to tell the difference between lesser and more advanced stages of endometriosis, and they were able to identify endometriosis at different points in the menstrual cycle.
“We’re looking ahead to potentially being able to do a test for endometriosis in the office, as opposed to general anesthesia in the operating room,” Giudice said. Clinicians could insert a thin plastic catheter through the cervix into the uterus to remove a sample of endometrial cells, a procedure that takes about 5-10 minutes, Giudice explained.
In the study, researchers found distinct patterns of gene expression involving inflammation and in activating the immune system in the endometrium of women with endometriosis. They also reported specific patterns of gene expression involved in building new blood vessels. Women with uterine fibroids and other pelvic disorders also showed signs of immune activation, although the gene expression in these conditions differed from that in women with endometriosis, they noted.
With findings in hand, the Reproductive Medicine Network, funded by the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development, has begun a multisite clinical trial that will test the method in a larger number of volunteers, said Louis DePaolo, PhD, chief of the NICHD Fertility/Infertility Branch and a coauthor of the current study.
What are the options?
What treatments are available to treat pain linked with endometriosis? The levonorgestrel intrauterine system has been used successfully to treat symptomatic endometriosis.4,5 The contraceptive injection subcutaneous depot medroxyprogesterone acetate (DMPA-SC, Depo-SubQ Provera 104, Pfizer, New York City) was given Food and Drug Administration approval in 2005 for treatment of pain related to endometriosis after research indicated it was as effective as leuprolide acetate, a gonadotropin-releasing hormone (GnRH) analog, for such use.6
According to Contraceptive Technology, combined oral contraceptives also decrease the menstrual pain suffered by women with endometriosis. This benefit is enhanced by use of extended-cycle pills, which reduce the number of painful episodes women have.7 The contraceptive implant (Nexplanon, Merck, Whitehouse Station, NJ) also might be effective in reducing pelvic pain associated with endometriosis.8(Read about upcoming treatments in the Contraceptive Technology Update article, “Endometriosis is the focus of new scientific research,” May 2014,)
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Buck Louis GM, Hediger ML, Peterson CM, et al. ENDO Study Working Group. Incidence of endometriosis by study population and diagnostic method: The ENDO study. Fertil Steril 2011; 96(2):360-365.
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American College of Obstetricians and Gynecologists. Practice bulletin no. 114: Management of endometriosis. Obstet Gynecol 2010; 116(1):223-236.
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Tamaresis JS, Irwin JC, Goldfien GA, et al. Molecular classification of endometriosis and disease stage using high-dimensional genomic data. Endocrinology 2014; 155(12):4986-4999.
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Bahamondes L, Petta CA, Fernandes A, et al. Use of the levonorgestrel-releasing intrauterine system in women with endometriosis, chronic pelvic pain and dysmenorrhea. Contraception 2007; 75(6 Suppl):S134-S139.
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Petta CA, Ferriani RA, Abrao MS, et al. Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis. Hum Reprod 2005; 20(7):1993-1998.
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Schlaff WD, Carson SA, Luciano A, et al. Subcutaneous injection of depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis-associated pain. Fertil Steril 2006; 85(2):314-325.
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Nelson AL, Cwiak C. Combined oral contraceptives. In: Hatcher RA, Trussell J, Nelson AL, et al. Contraceptive Technology: 20th revised edition. New York: Ardent Media; 2011.
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Walch K, Unfried G, Huber J, et al. Implanon versus medroxyprogesterone acetate: Effects on pain scores in patients with symptomatic endometriosis — a pilot study. Contraception 2009; 79(1):29-34.
