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Breaking the Endo Cycle

April 2003

by Amanda Gallagher

A thousand metal staples clamp into a womanís side as she waits for the inevitable jab of an acutely sharpened dagger. The torture isnít literal Ė but the pain is very real. Itís the pain a woman with endometriosis may experience every month.

The gynecological disease affects an estimated 5 percent to 7 percent of all women, yet it is rarely discussed and often misdiagnosed. It occurs when tissue that typically lines the uterus begins to grow outside of the uterus and attach to other parts of the pelvic cavity, such as the ovaries and intestines, ultimately leading to scarring and inflammation.

Endometriosis can cause severe, even debilitating, menstrual pain, gastrointestinal problems, fatigue and worse. "I couldnít get pregnant," said Vicky Karleskint, a San Antonio woman who suffered from the disease.

While treatment options are available, there is no known cause or cure. But that may change, thanks to the groundbreaking research of Robert Schenken, M.D., professor and chair of obstetrics and gynecology, and his co-investigator, Craig Witz, M.D., associate professor, obstetrics and gynecology and chief of the division of reproductive endocrinology and infertility.

The National Institutes of Health awarded Dr. Schenken an $894,000 grant to pinpoint the exact cause of endometriosis. He and Dr. Witz are examining factors that lead to initiation of the earliest endometriosis lesions.

"We are investigating CD44, which is a protein that is expressed on many different cell types, including endometrial cells," Dr. Schenken said.

Endometrial cells are the cells that line the uterus. Each month these cells accumulate, and if a woman isnít pregnant, they shed through her cervix during menstruation. It sounds simple, but the monthly cycle becomes a little more complicated.

"When the endometrial cells shed, they donít all go out the cervix with the menstrual blood. Some flow backward through the fallopian tubes," Dr. Schenken said. "This is called retrograde menstruation. Almost every woman has some retrograde menses, but not every woman will develop endometriosis."

That may be because of altered CD44 in the patients who develop endometriosis. Drs. Schenken and Witz believe an altered form of the protein causes endometrial cells to stick to peritoneal cells, which line the abdominal cavity. If a woman has an altered form of CD44, her endometrial cells will clump together during retrograde menstruation and form growths or lesions outside of the uterus.

"When the cells stick to the peritoneum, they begin to establish their own blood supply. The blood supply is regulated by estrogen," Dr. Schenken said.

The resulting growths may bleed at the time of menstruation. Since the blood canít exit the body through the cervix, the growth bleeds internally, causing inflammation, pain and infertility.

While the condition is excruciating for many women, itís not easy to diagnose.
"It is enigmatic in that some patients who have developed severe endometriosis have very few symptoms, while others with early stages of the disease are in extreme pain," Dr. Witz said.

Karleskint was a classic example. "I had monthly pain, but I thought it was normal," she said. "I didnít know I had endometriosis until I couldnít get pregnant and went to fertility specialists. Nobody noticed anything until Dr. Witz performed an exploratory surgery."

Dr. Witz told Karleskint her case was quite advanced. Her ovary was attached to her intestines, her fallopian tubes were attached to her pelvic wall and one tube was completely closed. "I was very surprised, but in a way, I was relieved," Karleskint said. "I finally had some answers. I was thankful they got it in time before I had to have a complete hysterectomy."

Dr. Witz was able to remove the excess tissue with laparoscopic surgery. Karleskint is now the mother of a 4-year-old little girl. But her battle isnít over. She would like to have another child, but in order to treat the endometriosis she must either take hormone therapy that prevents fertility or face another surgery down the road.

That is why the work of Drs. Schenken and Witz is so important. "Nobody knows the exact genetic nature, but if we can determine the specific factors involved in CD44, we can conceivably develop new medical approaches to prevent endometrial cells from attaching," Dr. Schenken said.

Already, the teamís work has gained critical acclaim in the medical community. Their findings made the covers of Fertility and Sterility and Human Reproduction, both official publications of medical societies. Theyíve also produced an award-winning video on the topic.

"I believe that we are cutting-edge," Dr. Witz said. "It has been controversial as to whether endometrial cells would attach to mesothelial cells (cells lining the abdominal organs). Other groups declared this would happen only if there was damage to the mesothelial cells. We have gone to great lengths to prove this is
not true."

Those lengths will eventually stretch how doctors can treat, prevent or even cure the disease. "I would hope there would be better treatments in the future and surgery wouldnít be the only option," Karleskint said.

Her hopes could soon come true. The study began in April 2003 and will last four years Ė a relatively short time in a journey that could finally put an end to endometriosis.


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