Driven by the pain of endometriosis

In endometriosis, tissue resembling the lining of the uterus, which is shed each month during menstruation, grows outside of it, mainly in the pelvis. The misplaced tissue can lead to intense pain during periods; chronic pelvic pain; pain with sex, defecation or urination; and infertility. The causes of endometriosis remain murky, and the only treatments target the pain, not the origins of the disease. 

Now the University of Cincinnati College of Medicine's Katie Burns, PhD, is helping uncover the role of the immune system in endometriosis, while managing the disease herself.

The associate professor and director of the Division of Environmental Genetics and Molecular Toxicology in the Department of Environmental and Public Health Sciences was recently the subject of an in-depth feature in Science Magazine.

Burns told reporter Meredith Wadman that when she was a teenager and the pain of endometriosis became agonizing, she would crawl under her bed and lie on her stomach on the wood floor. She’d clutch a calculator and do math problems to distract herself from the feeling that invisible hands were wringing out her uterus like a washcloth.

Her parents shuttled her from doctor to doctor searching for the source of her pain, which became a constant presence once she got her period on the eve of her 13th birthday.

“They said it was growing pains. It was normal. It was nothing,” recalled Burns, now 47. “They took me out of the room and said to my parents: ‘This is psychological. She’s seeking help.’"

It wasn’t until Burns went away to college that she learned from her roommates that the pain that kept her in her room on Friday nights and that several times sent her to the emergency room wasn’t normal. Nor were the periods that soaked a super-plus tampon every hour, or her need to take ibuprofen constantly to be able to function.

That pain arises from inflammation and scarring in and around endometriosis lesions, and from nerves that infiltrate them. Most lesions are superficial, growing on the peritoneal membrane, which lines the walls of the pelvis, envelops the ovaries and the fallopian tubes, and drapes parts of the ureters, bladder and bowel. The ovaries are a common site, and lesions can develop into large cysts called endometriomas. The aberrant tissue can also reach deep into the muscular walls of the bowel, bladder and vagina. And it commonly affects certain ligaments that hold the uterus in place. 

Eventually, a gynecologist located a mass sitting under the skin on the right side of Burns's pubic area. Weeks before her 21st birthday, Burns underwent surgery and the mass was extracted. It relieved some of the pain. It also offered validation. Microscopic examination of the mass showed Burns had endometriosis.

“It was a relief,” she recalled. "There was actually something that was wrong. I wasn’t making this up.” 

Like many with endometriosis, Burns was disappointed by the few treatment options. Standard birth control pills combining a synthetic version of estrogen with the progesterone analog progestin are a first-line treatment that reduces natural estrogen production to ease pain. Other hormone-based therapies come with their own hazards including hot flashes, night sweats, and with prolonged use, bone thinning.

Surgery is still required for a diagnosis of endometriosis. It can also ease symptoms by removing lesions, although they can be exceedingly tricky to spot. Even after clean removals, the disease often recurs.

Late in her PhD program, Burns began to look for a postdoctoral position that would let her study endometriosis. That became a life spent in the lab, tracking the roots of the disease. She and others have set their sights on the immune system, revealing that it not only fails to clear the errant growths, but seems to be essential to their establishment and flourishing, as lesions become epicenters of chronic, low-grade inflammation that can affect the whole body.

Although many labs studying the immune system in endometriosis were focused on macrophages, which are hardy and long-lived in the lab, making them easier to study, Burns decided to focus on neutrophils — “a cell type that people have really thrown out,” literally and figuratively, she says, partly because they are famously hard to keep alive.

In 2020, Burns’s team began the painstaking work of studying neutrophils collected from menstrual fluid samples. 

Under a microscope, the neutrophils from the menstrual fluid of women without endometriosis had plump, purple-stained nuclei, each with the usual two or three lobes. But in the fluid of those with endometriosis, these nuclei had four, five or even more lobes, yet they were condensed and shrunken. 

“It shocked us. It’s absolutely beautiful,” Burns said.

Read how this discovery is leading to a non-invasive diagnostic test and the rest of the article.

Featured image at top: Katherine (Katie) Burns, PhD. Photo/Joe Fuqua/University of Cincinnati.