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Stanford-Led Team Makes Strides Toward Better Endometriosis Diagnosis, Treatment.

News Editors/Health/Medical Writers

STANFORD, Calif.--(BUSINESS WIRE)--June 16, 2003

A Stanford-led team of researchers has opened the way to a new approach for diagnosing and treating endometriosis. The study, in the July issue of Endocrinology, used microarray technology to identify genes likely to contribute to the disease, which affects 10 to 15 percent of women of reproductive age and 35 to 50 percent of women with infertility.

"This new information has great potential to improve diagnosis of endometriosis," said senior author Linda Giudice, M.D., Ph.D., professor of obstetrics and gynecology at the Stanford School of Medicine. "The findings suggest targets for new drugs that could minimize the disease," added Giudice, who directs the division of reproductive endocrinology and infertility at the school. Stanford researcher Lee Kao, M.D., Ph.D., led the study, collaborating with Giudice and others at Stanford along with researchers from the University of California-San Francisco, Vanderbilt University and the University of North Carolina-Chapel Hill.

In endometriosis, endometrium tissue normally found lining the uterus grows elsewhere, spreading to other areas within a woman's pelvic cavity and abdomen -- usually the fallopian tubes, ovaries and intestines. While some women with endometriosis have no symptoms, many experience pelvic pain and severe menstrual cramps.

Diagnosing endometriosis usually involves surgery and general anesthesia; treatment typically involves surgical removal of tissue or medication. Both routes pose problems. The condition often relapses after surgery and the medications have undesirable side effects and are sometimes ineffective.

In the study, researchers collected biopsies of endometrium from 15 volunteers, eight with endometriosis and seven without, during the several-day window in a menstrual cycle when a fertile woman's uterus is receptive to an embryo's implantation. Their goal was to uncover differences in gene expression in the two groups of women.

The scientists used a microarray, also known as a gene chip, to simultaneously screen 12,868 genes -- about a third of the predicted number in the human genome. Each gene tells the body how to make RNA, which in turn makes one or more specific proteins, a process called gene expression. Proteins then carry out specific activities in the body's cells.

The screening revealed 91 genes that had more than a twofold increase in gene expression in women with endometriosis compared to those without the disease, and 115 genes that had more than a twofold decrease.

The researchers next zeroed in on genes that seem especially relevant to endometriosis-related infertility. To do this, they combined their new findings with findings from their earlier study, which used microarray screening to compare gene expression in fertile women during their receptive and non-receptive periods.

Analyzing these findings together revealed 12 genes of particular interest for endometriosis-related infertility. Eight sparked interest because their expression increased during the window of implantation in women without endometriosis but decreased at that time in women with the disease. Three other genes were noteworthy for the opposite reason: their expression decreased in healthy women but increased in women with endometriosis. Another gene, which decreased expression during the window of implantation in healthy women, decreased further in women with the disease.

"These genes are likely to have a role in the development of the disease and its related implantation failure," said Kao. The identified genes make proteins involved in important cellular processes, including embryo attachment, embryo toxicity, immune function, programmed cell death, sex hormone regulation and blood vessel development.

Next, the researchers plan to validate their findings and follow new leads. "These are exciting findings and they can potentially lead to new tools for diagnosis and treatment of endometriosis and infertility. This is brand new information," said Kao.

One of the first projects will be to test a microarray designed for diagnosing endometriosis, which could make diagnosis a less-invasive, less-expansive process. Diagnosis with a chip would rely on just a blood test or a biopsy; while it remains unclear which technique would be better, either would represent an improvement over the current method of surgery under general anesthesia. "We have put a diagnostic chip together conceptually and hope to have it made soon," said Giudice, adding that the consortium plans to test the chip's reliability. She estimates it will be available for widespread use in a few years if testing goes well.

More information about endometriosis is available from the government publication Endometriosis, at http://www.nichd.nih.gov/publications/pubs/endometriosis.pdf. For additional information, contact the Endometriosis Association, 8585 North 76th Place, Milwaukee, WI 53223; 414/355-2200; http://www.EndometriosisAssn.org/.

This research was funded by the National Institutes of Health; the National Institute for Child Health and Human Development; the NIH Office of Women's Health Research; the NIH Women's Reproductive Health Research Career Development Program; the German Research Foundation; and the Endometriosis Association.

Stanford University Medical Center integrates research, medical education and patient care at its three institutions -- Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu.
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Date:Jun 16, 2003
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