Urinary Metabolomics Identifies a Molecular Correlate of Interstitial Cystitis/Bladder Pain Syndrome in a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Cohort.
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a poorly understood syndrome affecting up to 6.5% of adult women in the U.S. The lack of broadly accepted objective laboratory markers for this condition hampers efforts to diagnose and treat this condition. To identify biochemical markers for IC/BPS, we applied mass spectrometry-based global metabolite profiling to urine specimens from a cohort of female IC/BPS subjects from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. These analyses identified multiple metabolites capable of discriminating IC/BPS and control subjects. Of these candidate markers, etiocholan-3α-ol-17-one sulfate (Etio-S), a sulfoconjugated 5-β reduced isomer of testosterone, distinguished female IC/BPS and control subjects with a sensitivity and specificity >90%. Among IC/BPS subjects, urinary Etio-S levels are correlated with elevated symptom scores (symptoms, pelvic pain, and number of painful body sites) and could resolve high- from low-symptom IC/BPS subgroups. Etio-S-associated biochemical changes persisted through 3-6months of longitudinal follow up. These results raise the possibility that an underlying biochemical abnormality contributes to symptoms in patients with severe IC/BPS.
Center for Women's Infectious Diseases Research, Washington University in St. Louis School of Medicine, St. Louis, MO, United States; Division of Infectious Diseases, Washington University in St. Louis School of Medicine, St. Louis, MO, United States; Department of Internal Medicine, Washington University in St. Louis School of Medicine, St. Louis, MO, United States.
Kaveri S
KS
Parker
Department of Internal Medicine, Washington University in St. Louis School of Medicine, St. Louis, MO, United States.
Jan R
JR
Crowley
Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, United States.
Alisa J
AJ
Stephens-Shields
Department of Pathology, University of Colorado, Aurora, CO, United States.
Adrie
A
van Bokhoven
Department of Pathology, University of Colorado, Aurora, CO, United States.
M Scott
MS
Lucia
Division of Urologic Surgery, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, United States; Department of Anesthesiology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States.
H Henry
HH
Lai
Division of Urologic Surgery, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, United States.
Gerald L
GL
Andriole
Division of Infectious Diseases, Department of Medicine, University of Miami School of Medicine, Miami, FL, United States.
Thomas M
TM
Hooton
Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.
Chris
C
Mullins
Center for Women's Infectious Diseases Research, Washington University in St. Louis School of Medicine, St. Louis, MO, United States; Division of Infectious Diseases, Washington University in St. Louis School of Medicine, St. Louis, MO, United States; Department of Internal Medicine, Washington University in St. Louis School of Medicine, St. Louis, MO, United States. Electronic address: jhenderson@DOM.wustl.edu.
Jeffrey P
JP
Henderson
D000328:Adult; D015415:Biomarkers / Q000652:urine; D015331:Cohort Studies; D018856:Cystitis, Interstitial / Q000175:diagnosis / Q000652:urine*; D005260:Female; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D010147:Pain Measurement; D013256:Steroids / Q000652:urine*; D013431:Sulfates / Q000652:urine*
D015415:Biomarkers; D013256:Steroids; D013431:Sulfates