Hum. Reprod. Advance Access published online on June 23, 2009
Human Reproduction, doi:10.1093/humrep/dep195
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High serum follistatin levels in women with ovarian endometriosis
1 Division of Obstetrics and Gynecology, Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Policlinico ‘Le Scotte’, Siena, Italy 2 Department of Obstetrics and Gynecology, University of Minas Gerais, Belo Horizonte, Brazil 3 Endometriosis Unit, University of São Paulo, São Paulo, Brazil 4 Day Surgery Free-Standing Unit ‘Palagi’, Florence, Italy
5 Correspondence address. Tel: +39-0577-586-649; Fax: +39 0577 233.454; E-mail: petraglia{at}unisi.it
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
Key words: follistatin/endometriosis/CA-125/ovarian cyst/diagnostic accuracy
Submitted on August 7, 2007; resubmitted on March 13, 2009; accepted on March 26, 2009.