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


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.
Yuan
Peng
P
Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, No. 17 Changle West Road, Xi'an, Shaan'xi 710032, China. ypfmmu@gmail.com
Huang
Yanhong
Y
Wu
Hong
H
Teng
Zenghui
Z
Zhang
Jianfang
J
Xin
Xiaoyan
X
D000818:Animals; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004715:Endometriosis / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D016912:Levonorgestrel / Q000008:administration & dosage*; D008863:Microspheres; D011247:Pregnancy; D011555:Pseudopregnancy / Q000139:chemically induced*; D011817:Rabbits
D016912:Levonorgestrel