Hum. Reprod. Advance Access published online on November 7, 2009
Human Reproduction, doi:10.1093/humrep/dep386
Induction of a local pseudo-pregnancy via levonorgestrel-loaded microspheres for the treatment of endometriosis in a rabbit model
1 Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, No. 17 Changle West Road, Xi'an, Shaan'xi 710032, China 2 Department of Pharmacology, Fourth Military Medical University, No.17 Changle West Road, Xi'an, Shaan'xi 710032, China
3 Correspondence address. Tel: +86-13772138327; E-mail: ypfmmu{at}gmail.com (P.Y.)/xin_xiaoyan{at}126.com (X.X.)
BACKGROUND: Endometriosis is a chronic disease that responds to systemic pseudo-pregnancy therapy. However, side effects limit their long-term use, and recurrence often occurs after cessation of medication. Reducing side effects whereas improving therapeutic efficacy of pseudo-pregnancy therapy seems contradictory, but appealing. In order to address this dilemma, the efficacy and side effects of local pseudo-pregnancy therapy were investigated for the first time in an endometriosis animal model.
METHODS AND RESULTS: Levonorgestrel-loaded polylactic acid microspheres (LNG-microspheres) were prepared by using an oil-in-water emulsification–solvent evaporation method. Rabbits with experimental endometriosis were randomized to treatment with local pseudo-pregnancy therapy, local blank microspheres, systemic pseudo-pregnancy therapy, ovariectomy or the control. Local pseudo-pregnancy was induced by injection of LNG-microspheres directly into endometrial cysts. Compared with the systemic pseudo-pregnancy group, significantly higher intra-cystic drug levels were maintained for at least 6 months with much lower serum levels in the local pseudo-pregnancy group (P < 0.01). The high intra-cystic levonorgestrel simulated a state of potent pregnancy, which induced size reductions and endometrial atrophy comparable to those of ovariectomy. Moreover, major metabolic parameters and ovarian function were not disturbed by local pseudo-pregnancy therapy.
CONCLUSIONS: Induction of a local pseudo-pregnancy could achieve therapeutic efficacy comparable to that of ovariectomy without provoking any marked side effects in a rabbit endometriosis model. Thus it may be a preferable option for patients with endometriosis.
Key words: endometriosis/levonorgestrel/local pseudo-pregnancy/microsphere/rabbit
Submitted on August 14, 2009; resubmitted on September 29, 2009; accepted on October 8, 2009.