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
Kaveri S. Parker,
Jan R. Crowley,
Alisa J. Stephens-Shields,
Adrie van Bokhoven,
M. Scott Lucia,
H. Henry Lai,
Gerald L. Andriole,
Thomas M. Hooton,
Chris Mullins,
Jeffrey P. Henderson
Affiliations
Kaveri S. Parker
Center for Women's Infectious Diseases Research, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
Jan R. Crowley
Department of Internal Medicine, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
Alisa J. Stephens-Shields
Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, United States
Adrie van Bokhoven
Department of Pathology, University of Colorado, Aurora, CO, United States
M. Scott Lucia
Department of Pathology, University of Colorado, Aurora, CO, United States
H. Henry Lai
Division of Urologic Surgery, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
Gerald L. Andriole
Division of Urologic Surgery, Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
Thomas M. Hooton
Division of Infectious Diseases, Department of Medicine, University of Miami School of Medicine, Miami, FL, United States
Chris Mullins
Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States
Jeffrey P. Henderson
Center for Women's Infectious Diseases Research, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
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 3–6 months of longitudinal follow up. These results raise the possibility that an underlying biochemical abnormality contributes to symptoms in patients with severe IC/BPS.
