Antiproliferative effects of anastrozole, methotrexate, and 5-fluorouracil on endometriosis in vitro and in vivo.
Fertility and sterility 2009 Dec 31; In press
Ngô C, Nicco C, Leconte M, Chéreau C, Weill B, Batteux F, Chapron C
Université Paris Descartes, Faculté de Médecine, EA 1833, ERTi, AP-HP Hôpital Cochin, Paris; Université Paris Descartes, Faculté de Médecine, AP-HP Hôpital Cochin, Service de gynécologie obstétrique II et Médecine de la Reproduction, Paris.
OBJECTIVE: To investigate the effects of antiproliferative drugs (anastrozole, methotrexate, and 5-fluorouracil [5-FU]) on the proliferation of endometriotic cells in vitro and in vivo. DESIGN: Ex vivo study on human endometrial and endometriotic cells in culture; establishment of a murine model using mice implanted with human endometriosis. SETTING: University research center. PATIENT(S): Ten patients with ovarian endometrioma, 10 patients with deep infiltrating endometriosis, and 10 patients without endometriosis. INTERVENTION(S): Stromal and epithelial cells were extracted from endometrial and endometriotic biopsies from patients with endometriosis and from patients without endometriosis. Cells were treated in vitro with anastrozole, methotrexate, progesterone, or 5-FU. Human endometriotic lesions were implanted in nude mice. Mice were treated with 5-FU or phosphate-buffered saline during 4 weeks before sacrifice and extraction of the endometriotic implants. MAIN OUTCOME MEASURE(S): Stromal and epithelial cell proliferation and pathology score of endometriotic implants. RESULT(S): Although anastrozole, methotrexate, and progesterone were ineffective, 5-FU significantly decreased the proliferation of endometriotic cells in vitro and controlled the growth of both cells from ovarian endometrioma and deep infiltrating endometriosis. CONCLUSION(S): Considering common features between endometriotic cells and tumor cells, the use of 5-FU could be an option in the management of severe endometriosis.
Keywords: anastrozole methotrexate fluorouracil endometriosis