The aromatase inhibitor letrozole reduces adhesion formation after intraperitoneal surgery in a rat uterine horn model

Objective

To investigate, in an experimental animal study, the effects of letrozole and tamoxifen in the reduction of adhesion formation following abdominopelvic surgery.

Study design

Thirty female Wistar albino rats were included and divided into three groups. One group received 500 μg/d tamoxifen and a second group received 1 mg/kg/d letrozole through an enteric tube. A third group did not receive any drugs and served as the control group. On the fifth day, a laparotomy was performed and the right uterine horn was injured by monopolar cautery. The left uterine horn was incised with a scalpel and sutured. The preventive therapy protocols were continued for 7 days after surgery. On the 14th day after first surgery the animals were sacrificed, and the intraperitoneal macroscopic adhesion formation and microscopic adhesion features were evaluated. The Kruskal–Wallis test was used to compare the scores of the macroscopic adhesion scores and histologic features among the three groups, followed by a post hoc Mann–Whitney test. The total histological score was analyzed with a one-way ANOVA, followed by post hoc Bonferroni correction tests. p values ≤0.05 were considered statistically significant. The level of significance was set at p ≤ 0.016 for the post hoc tests.

Results

The letrozole and tamoxifen groups had significantly lower adhesion scores for the right uterine horn than the control group (p = 0.005 and p = 0.013, respectively). For the left horn, however, only the letrozole group had a lower macroscopic adhesion score than the controls (p = 0.011). The total histological score was significantly lower in the letrozole group than in the control group (p = 0.014), but no differences were found between the tamoxifen group and the control group (p = 0.954). Inflammation, fibroblastic activity, collagen formation and vascular proliferation were significantly lower in the letrozole group compared with the control group (p < 0.05). The foreign body reactions were similar among the three groups (p > 0.05). Tamoxifen administration did not result in any significant effects on the histological scores (p > 0.05).

Conclusion

Letrozole resulted in a significant decrease in postoperative macroscopic adhesion formation and the total histological scores, but tamoxifen did not demonstrate a similar effect on the histological scores.