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

Peng Yuan, Yuan P, Yanhong Huang, Huang Y, Hao Wu, Hong Wu, Wu H, Zhongzhao Teng, Zenghui Teng, Teng Z, Jiawei Zhang, Jianfang Zhang, Zhang J, Xiaoyan Xin, Xin X
Human Reproduction · 2009 · vol. 25(2) , pp. 462–469 · doi:10.1093/humrep/dep386 · PMID:19897855 · W2103860711
Lab / animal OA: bronze CC0 ⤵ 10 in-corpus citations
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Levonorgestrel microspheres injected into endometrial cysts reduced endometriosis lesion size comparably to ovariectomy with minimal systemic side effects in a rabbit model.

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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.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Levonorgestrel Pseudopregnancy Animals Animals Disease Models, Animal Disease Models, Animal Drug Delivery Systems Drug Delivery Systems Endometriosis Endometriosis Endometriosis Female Female Levonorgestrel Levonorgestrel Microspheres Microspheres Pregnancy Pregnancy

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