Investigation of the Effects of Partial Estrogen Antagonist Tamoxifen and Aromatase Inhibitor Letrozole on the Endometrium in Rats and Determination of the Effects in Combination with Nonselective Cox Inhibitor Acetylsalicylic Acid (Aspirin)

Abstract

Objective : This study investigates the effects of tamoxifen, a selective estrogen receptor modulator, and letrozole, an aromatase inhibitor, on the endometrium in a rat model. It further evaluates the combined impact of these drugs with acetylsalicylic acid (aspirin), a non-selective COX inhibitor, through immunohistochemical and biochemical analyses, aiming to compare endometrial alterations and the potential mitigating effects of aspirin. Methods : Seventy female rats were divided into seven groups receiving tamoxifen, letrozole, their combinations with aspirin, and control treatments. Endometrial tissues were analyzed for VEGF, COX-2, Ki-67, BCL-2, and PECAM-1 expression using immunohistochemistry, while serum VEGF-C levels were quantified via ELISA. Statistical comparisons were conducted across groups. Results : Tamoxifen significantly increased VEGF and COX-2 expression in the endometrium compared to controls, whereas aspirin co-administration significantly reduced these levels. No significant Ki-67 expression changes were observed in the glandular epithelium or stroma. Tamoxifen did not affect BCL-2 expression in the epithelium but decreased stromal expression. PECAM-1 expression remained unchanged across groups, and tamoxifen-induced serum VEGF-C elevation was not statistically significant. Conclusions : Tamoxifen increases VEGF and COX-2 expression, potentially contributing to endometrial pathologies, while aspirin co-administration effectively mitigates these effects, suggesting its protective role against uterine complications. Letrozole demonstrated minimal endometrial impact, reinforcing its favorable safety profile. The combination of tamoxifen and aspirin may represent a viable strategy to alleviate endometrial side effects in clinical applications.