Induction of a local pseudo-pregnancy via levonorgestrel-loaded microspheres for the treatment of endometriosis in a rabbit model.

Abstract

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.

• Authors: Peng Yuan, Yanhong Huang, Hong Wu, Zenghui Teng, Jianfang Zhang, Xiaoyan Xin
• Journal: Human reproduction (Oxford, England) (Hum Reprod) Vol. 25 Issue 2 Pg. 462-9 (Feb 2010) ISSN: 1460-2350 [Electronic] England
• PMID: 19897855 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Levonorgestrel

Topics

• Animals
• Disease Models, Animal
• Drug Delivery Systems
• Endometriosis (drug therapy, pathology)
• Female
• Levonorgestrel (administration & dosage)
• Microspheres
• Pregnancy
• Pseudopregnancy (chemically induced)
• Rabbits