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“For a scientist, it’s fascinating the way so many systems and influences seem to be involved with the development of this disease, but that can also become distracting,” said Osteen, professor of Obstetrics and Gynecology, professor of Pathology, and director of Vanderbilt’s Division of Women’s Reproductive Health and Research Center, which houses the flagship academic research program of the Endometriosis Association, an international advocacy group.

With each completed menstrual cycle, the lining of the uterus, called the endometrium, builds up in preparation for pregnancy and then breaks down to be shed in menstruation. A great majority of women have retrograde menstruation, which permits some of the shed tissue to disperse through the pelvic cavity.

In endometriosis, wayward endometrial tissue implants outside the uterus, on the ovaries, fallopian tubes, the outer uterus and its supporting ligaments, the pelvic wall, intestines, bladder and points beyond. The implants build up and shed in rhythm with menstruation, the bleeding causes irritation and thus scarring, cysts, and the fusing or adhesion of normally separate tissues, including adhesions that block the reproductive tract. The pain of endometriosis may extend beyond the menstrual phase, and may include sharp pain during intercourse. Though primarily a disease of the reproductive years, it also can occur in adolescence before menstruation, and it’s by no means rare in menopausal women.

Endometriosis is the second most common cause of hysterectomy (fibroids are first). While the prevalence of endometriosis among infertile women is put at 40 percent, it’s commonly thought that somewhere around 10 percent of all women of childbearing age have the disease to one degree or another.

“We’ve had students working in our own lab who literally sit and rock from the pain,” Osteen said.

“In harsh cases, on a scale from 1 to 10, the pain is 15,” said Esther Eisenberg, M.D., professor of Obstetrics and Gynecology and the third member of Vanderbilt’s endometriosis team.

Osteen has led laboratory studies that have been highly influential for today’s emerging understanding of endometriosis. He is currently a primary investigator for three studies funded by the National Institutes of Health, including two Research Project Grants (R01) and an Interdisciplinary Research Consortium grant (U54): one study examines progesterone failure in the endometrium of patients with endometriosis; another examines the relationship between endometriosis and the failure of a protective anti-inflammatory protein called CD55; a third study examines whether environmental toxins play a role in endometriosis.

Bruner-Tran is the primary investigator for an NIH-funded study aimed at developing a new model of experimental endometriosis using genetically immune-compromised mice. These mice will allow closer examination of the role of the immune system in the pathophysiology of endometriosis.

The four grants are interactive, with Osteen and Bruner-Tran being co-investigators on each other’s grants.

“Translational research can only be successful when basic scientists have clinical partners like Esther. It is essential that physicians and scientists talk to one another,” Osteen said.

Endometriosis is a disease that wants not only to be felt, but to be ultimately seen as well. Definitive diagnosis entails visualization, the physician peering through an endoscope as the patient lies anesthetized.

The average time from onset to a diagnosis is currently about seven years. Those years may or may not be pain ridden. Some of the possible sites for implantation of the disease are fully wired for pain, others much less so, and in any given case there’s no reason to expect severity of pain to correlate with severity of disease. In fact, it’s possible to have considerable damage while remaining pain free.

It would be madness for doctors to order endoscopy for every patient who reports menstrual pain. On the other hand, the pain of undiagnosed endometriosis has been linked to cases of suicide in younger women, Osteen said. Bruner-Tran said that even though there’s no cure, some patients voice tremendous relief upon hearing their diagnosis, because their anguish at last is given a physical explanation.

“It’s really a hard disease to study, because you can’t get to it early on,” Eisenberg said.

There are a number of treatments that can hold the disease and its symptoms at bay, ranging from narcotics to birth control pills for suppression of periods in women not seeking pregnancy to laparoscopic surgery for clearing away implants and diseased tissue. Endometriosis is studied not in humans but in the lab. By the time a patient receives a diagnosis, no one is about to ask her to delay use of a known effective treatment to participate in a clinical trial.

For Osteen and Bruner-Tran, the cause of endometriosis remains elusive, but less so than a decade ago. The known and suspected factors still range from hormonal to immunological to genetic to environmental and epigenetic. The disease continues to invite inquiry of a range and complexity as rich and extended as any in today’s medicine. As findings from the lab have mounted, the character and causes of endometriosis have begun to attract greater interest from pharmaceutical companies, and morale among researchers is noticeably higher than it was a decade ago, Osteen said.

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