Study Focuses on Molecular Changes Associated With Different Kinds of Endometriosis Pain

Endometriosis affects up to 10% of women of reproductive age, yet the underlying molecular drivers of the disease are not well understood. The primary symptom of the disease is pelvic pain, which can severely impact a patient’s quality of life. In addition, endometriosis often leads to infertility.

Naoko Sasamoto, MD, PhD, MPH, a gynecologist and clinical oncologist at Brigham and Women’s Hospital, is focused on developing novel therapeutics that target the underlying causes of the disease.

Dr. Sasamoto recently published a study in Human Reproduction looking at proteomic profiles in blood plasma that are associated with different pain subtypes in adolescents and young adults with endometriosis. Current treatments are ineffective for many patients and have high recurrence rates.

“Seeing the devastating effects that endometriosis has had on so many women is very motivating to me and drives me to really understand this disease,” she says. “We hope that by learning more about what causes these different types of pain, we can develop a more personalized approach for treating patients.”

Correlating Types of Pain With Molecular Signatures

Not all people with endometriosis experience the same kind of pain. Some patients have pain only at certain times in their menstrual cycle. For others, the pain may be more frequent—and less predictable. Pain may also be associated with urination or bowel movements, especially during menstrual periods.

“Endometriosis is actually a very heterogeneous disease,” Dr. Sasamoto says. “What we showed in this paper is that distinct biological pathways may be associated with different pain subtypes.”

The findings not only shed light on what causes the disease’s symptoms but also suggest that different therapeutic approaches might be beneficial for treating different disease subtypes.

For example, endometriosis associated with acyclic pelvic pain was correlated with an upregulation of immune cell adhesion pathways. Meanwhile, patients with bladder pain had an upregulation of immune cell migration, and those with bowel pain had a downregulation of multiple immune pathways.

Cohort Study Provides Valuable Samples and Data

For their study, the researchers used samples collected through the Women’s Health Study: from Adolescence to Adulthood, which includes a longitudinal cohort of adolescents and young women who contributed biospecimens such as urine, saliva, blood, cells, tissue, and peritoneal fluid as well as information about their pain. Half of the 1,500 patients have confirmed endometriosis, and the other half are controls.

The SOMAScan proteomics assay, which can detect levels of 1,305 proteins, was used to analyze the patients’ plasma samples. The findings from the test were then correlated with patients’ reported symptoms.

The Women’s Health Study includes data and samples from patients diagnosed with endometriosis at a young age. “We’re very lucky to have access to data of these younger patients,” Dr. Sasamoto says. “Most patients are diagnosed in their mid-30s, and this study enables us to learn much more about how endometriosis develops in the early stages.”

Pursuing Personalized Treatments for Endometriosis

Currently, endometriosis therapy is similar for all patients, regardless of what kind of pain they are experiencing. Treatments consist of some type of hormone therapy along with medications for pain management. Many patients ultimately need surgery, and, even then, recurrence rates are high.

“This study suggests that we need to pay more attention to phenotyping the different kinds of pain and developing new treatments based on those phenotypes,” Dr. Sasamoto says. However, additional research is needed before more personalized treatments can be evaluated in clinical trials—something that she and her colleagues will continue to focus on.

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