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

Peng Yuan, Yanhong Huang, Hao Wu, Hong Wu, Zenghui Teng, Zhongzhao Teng, Jiawei Zhang, Jianfang Zhang, Xiaoyan Xin
Human Reproduction · 2009 · vol. 25(2) , pp. 462–469 · doi:10.1093/humrep/dep386 · PMID:19897855 · W2103860711
article OA: bronze CC0 ⤵ 10 in-corpus citations
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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 Disease Models, Animal Drug Delivery Systems Endometriosis Endometriosis Female Levonorgestrel Microspheres Pregnancy Pseudopregnancy Rabbits

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