High serum follistatin levels in women with ovarian endometriosis

Follistatin is an activin-binding protein produced by several tissues, including endometrium and endometriotic implants. We aimed to quantify follistatin in patients with ovarian endometriosis and investigate its value as a diagnostic marker. Women undergoing laparoscopic excision of ovarian endometrioma (n = 52) or other benign ovarian cysts (n = 52) were studied, plus women with non-ovarian endometriosis (n = 11) and healthy controls (n = 27). Serum was collected from all subjects, and peritoneal and cystic fluid from a subset with endometrioma. Follistatin was measured by enzyme-linked immunosorbent assay. The diagnostic accuracy of follistatin to detect endometrioma was evaluated by receiver operating characteristic (ROC) curve and compared with cancer antigen (CA)-125. Serum follistatin was increased in women with ovarian endometrioma (2080 +/- 94 pg/ml) compared with controls (545 +/- 49 pg/ml, P < 0.001), other benign ovarian cysts (795 +/- 60 pg/ml, P < 0.001) or non-ovarian endometriosis (1271 +/- 115 pg/ml, P < 0.001). Cystic fluid showed a higher concentration of follistatin (9850 +/- 4461 pg/ml) than peritoneal fluid (1885 +/- 261 pg/ml, P < 0.001) and serum (P < 0.001). Follistatin levels detected 48/52 cases of endometrioma (92% sensitivity) at 1433 pg/ml cut-off, corresponding to 92% specificity. CA-125 detected only 44% of endometriomas with 90% specificity. ROC curve comparison showed follistatin was more accurate than CA-125 to discriminate women with endometrioma either from controls or women with other benign ovarian cysts (P < 0.0001). Serum follistatin is increased in women with endometriosis and allows clear distinction between endometrioma and other benign ovarian cysts. Follistatin has the sensitivity and specificity to become a useful clinical marker of ovarian endometrioma.