Urocortin is a neuropeptide, member of the corticotropin-releasing hormone family, that is produced by the human endometrium. Ovarian endometrioma is a prevalent gynecologic disorder still lacking specific serum markers. In the present study we measured systemic levels of urocortin to assess the diagnostic performance of its determination in distinguishing endometriomas from other benign ovarian cysts. Plasma urocortin was measured by radioimmunoassay in women with ovarian endometrioma (n=40) and in women with benign, nonendometriotic ovarian cysts (n=40). The diagnostic accuracy of urocortin measurement was evaluated by receiver operating characteristic curve and compared with the standard marker, CA 125. To support the local origin of the peptide, we also evaluated its localization in endometriomas by immunohistochemistry and its concentrations in cyst fluid and peritoneal fluid of 12 women with endometrioma. Plasma urocortin levels were twice as high in women with endometrioma (median 49 pg/mL, interquartile range 41-63 pg/mL) than in the control group (19 [15-23] pg/mL, P<.001) and significantly higher in the cystic content of endometriomas than in the peritoneal fluid and plasma (P<.05). The peptide was immunolocalized in endometrioma glands and stromal capillary vessels. Elevated plasma urocortin levels detected 88% of the cases of endometrioma with 90% specificity, whereas CA 125 detected only 65% of the cases with the same specificity. Plasma urocortin is increased in women with endometriomas, and its measurement may be useful for the differential diagnosis of endometrioma compared with other benign ovarian cysts. II.