Evaluation of pharmacokinetics and safety of a long-term estradiol-releasing stent in rat uterine

PURPOSE: Intrauterine adhesion (IUA), often leading to gynecological complications including amenorrhea, abdominal pain and infertility, is frequently induced by injuries to the endometrium. Hence it would be of great benefit to take efforts to prevent adhesion after intrauterine operations. Orally administration of 17β-estradiol (E2) is commonly used to promote endometrium regeneration, but is limited by low concentrations at the injured sites. We aim at preparing an E2-releasing uterine stent, which could improve the efficiency of E2 therapy and be utilized for IUA prevention. METHODS: We designed a silicone rubber stent, which could be implanted in the uterine cavity and continuously release E2 in long term. Stents were placed in rodent uterine, and removed at different time points. Remaining E2 in stent was measured by high performance liquid chromatography (HPLC), and organ E2 concentrations were detected by enzyme-linked immuno sorbent assay (ELISA). Endometrium morphology was examined by histological staining of paraffin sections. RESULTS: Our stent showed a controlled release of E2 in rodent uterine for over 60 days, and significantly increased E2 concentration in serum and in situ uterine. After the stent was removed from uterine, E2 rapidly reverted to a normal level. Also, the stent did not induce pathological changes in endometrium. CONCLUSIONS: The uterine stent provided abundant local E2 in uterine cavity with satisfactory safety. The silicone rubber based E2-releasing uterine stent could be further advanced by adjusting its shape and E2 load for its clinical application, and might promisingly help lowering the incidence of IUA.