About one-third of patients with endometriosis have persistent pelvic pain after surgical treatment, and the severity of pain before surgery is no guide to postoperative outcomes. Currently there are no clinically useful biomarkers for predicting response to endometriosis surgery, but dysregulated lipid metabolism has been reported in these patients.
Naoko Sasamoto, MD, MPH, assistant professor in the Department of Obstetrics and Gynecology at Brigham and Women’s Hospital, Kathryn L. Terry, ScD, associate professor in the OB/GYN Epidemiology Center, and colleagues conducted the first study of the relationship between presurgical blood metabolites and postsurgical pain in adolescents and young women with endometriosis. Such patients typically present with severe pelvic pain and peritoneal lesions, therefore they would particularly benefit from prognostic biomarkers. In Fertility and Sterility, the team reports prospective data linking higher presurgical levels of multiple lipid metabolites to increased risk of persistent postsurgical pelvic pain one year post surgery.
The Women’s Health Study: From Adolescence to Adulthood is an ongoing, U.S.-based longitudinal study of 1,549 adolescents and women oversampled for those with endometriosis who were enrolled between 2012 and 2018. They completed an extensive questionnaire at baseline and return annual follow-up questionnaires.
To assess life-impacting pelvic pain, the participants are asked, “To what extent has your general pelvic/lower abdominal pain interfered with your normal social activities with work and school in the last 3 months?” In the current analysis, persistent postsurgical pain was defined as moderate to severe life-impacting pelvic pain one year after surgery.
The analysis included 180 study participants (mean age 18.7 years) that had laparoscopically confirmed endometriosis and had blood collected up to 90 days before surgery. By the revised American Society for Reproductive Medicine (rASRM) classification, 176 participants had stage I/II endometriosis at diagnosis, and four others had stage III/IV disease.
Persistent postsurgical pain was reported by:
- 36% of participants overall
- 36% of participants with rASRM stage I/II
- 25% of participants with rASRM stage III/IV disease
21 metabolites in presurgical blood samples were significantly associated with the risk of persistent pain. Of the 19 metabolites tied to increased risk (ORs of 1.42–1.74), 15 were lipid-related:
- Seven lysophosphatidylethanolamines (LPEs)
- Two lysophosphatidylcholines (LPCs)
- Three phosphatidylcholines
- Three other lipid derivatives
Fucose (OR, 0.69), an essential sugar involved in glycosylation reactions, and pregnenolone sulfate (OR, 0.64), a precursor of progesterone, were linked to decreased risk.
77 study participants had blood samples collected not just at baseline but also five to six months after surgery. Metabolites elevated at both time points were generally associated with persistent postsurgical pain in the same direction as in the main analysis.
Persistently high levels of three metabolites were significantly associated with an increased risk of persistent pain:
- C16:0 LPE (OR, 7.55)
- C18:3 LPE (OR, 15.3)
- C32:0 diglycerides (OR, 5.28)
Fucose (OR, 0.12) and pregnenolone sulfate (OR, 0.15) were again significantly associated with decreased risk.
While validation in independent datasets is needed, these findings indicate plasma metabolites are promising biomarkers to identify adolescents and young adults with endometriosis who may have persistent pelvic pain after surgery.
Previous reports have indicated interleukin-1β, interleukin-6, and tumor necrosis factor-α contribute to endometriosis pain. It’s possible that elevation of LPEs and LPCs reflects upregulation of prostaglandin synthesis triggered by these pro-inflammatory mediators, an insight that may have therapeutic implications.