Presurgical blood metabolites and risk of postsurgical pelvic pain in young patients with endometriosis

Abstract

Objective: To identify metabolites in presurgical blood associated with risk of persistent postsurgical pelvic pain 1 year after endometriosis surgery in adolescent and young adult patients.

Design: Prospective observational study within the Women's Health Study: From Adolescence to Adulthood, a US-based longitudinal cohort of adolescents and women enrolled from 2012-2018.

Setting: Two tertiary care hospitals.

Patient(s): Laparoscopically confirmed endometriosis patients (n = 180) with blood collected before their endometriosis surgery. Of these, 77 patients additionally provided blood samples 5 weeks to 6 months after their surgery. We measured plasma metabolites using liquid chromatography tandem mass spectrometry, and a total of 390 known metabolites were included in our analysis.

Intervention(s): None.

Main outcome measure(s): Persistent postsurgical pelvic pain, defined as severe, life-impacting pelvic pain 1 year after endometriosis surgery.

Result(s): Most patients (>95%) were at stage I/II of the revised American Society for Reproductive Medicine classification. Their average age at diagnosis was 18.7 years, with 36% reporting persistent postsurgical pelvic pain. Of the 21 metabolites in presurgical blood that were associated with risk of persistent postsurgical pelvic pain, 19 metabolites, which were mainly lipid metabolites, were associated with increased risk. Only 2 metabolites-pregnenolone sulfate (odds ratio = 0.64, 95% confidence interval = 0.44-0.92) and fucose (odds ratio = 0.69, 95% confidence interval = 0.47-0.97)-were associated with decreased risk. Metabolite set enrichment analysis revealed that higher levels of lysophosphatidylethanolamines (false discovery rate = 0.01) and lysophosphatidylcholines (false discovery rate = 0.01) in presurgical blood were associated with increased risk of persistent postsurgical pelvic pain.

Conclusion(s): Our results suggest that dysregulation of multiple groups of lipid metabolites may play a role in the persistence of pelvic pain postsurgery among young endometriosis patients.

Keywords: Adolescent; biomarkers; endometriosis; metabolomics; postsurgical pelvic pain.

Figure 1.. Metabolites associated with risk of persistent post-surgical pelvic pain at one-year after endometriosis surgery in the A2A (n=180).

Odds ratios and 95% confidence intervals per 1 standard deviation increase in metabolite levels are presented for the 21 metabolites associated with risk of severe pelvic pain at one-year after surgery (p-value < 0.05). All estimates were adjusted for age, fasting status, and pelvic pain severity at baseline.

Figure 2.. Metabolite set enrichment analysis (MSEA) results on enriched metabolite groups associated with persistent post-surgical pelvic pain at one-year after endometriosis surgery.

Red shades represent positive coefficients while blue shades represent negative coefficients. Significance of the association is overlaid on the heat map as follows: ** FDR<0.05, * FDR<0.20.