Effect of aromatase inhibitors on the endometrium and ovary with their possible role in ovulation in adult albino rats: a histological, immunohistochemical, morphometric, and hormonal assay

ABSTRACT

Aromatase inhibitors act by inhibiting estrogen synthesis and depletion of its concentrations in the circulation. The aim of the study was to investigate the effect of exemestane and letrozole on the endometrium and ovary with their possible role in ovulation in adult albino rats. Thirty adult female albino rats were used and divided into control and experimental groups. Rats in the experimental group were further divided into subgroup IIA and subgroup IIB. In subgroup IIA each rat was given exemestane at 1 mg/kg/day and in subgroup IIB each rat was given letrozole at 5 mg/kg/day by means of a gastric tube for five consecutive ovarian cycles. Specimens from their ovaries and endometrium were taken and prepared for H and E staining and for immunohistochemical staining for vascular endothelial growth factor study. Morphometric study of endometrial thickness and surface area percentage of immunoreaction in the endometrium was evaluated. Hormonal assay of luteinizing hormone and follicular stimulating hormone was carried out. Significant decrease in endometrial thickness was observed in the exemestane-treated group. The letrozole-treated group revealed significantly thickened endometrium. The exemestane-treated group showed markedly disturbed ovarian architecture in the form of thickened germinal epithelial cell layer and multiple corpora lutea with atretic follicles. The letrozole-treated group revealed an ovarian cortex with multiple stages of follicular development. The vascular endothelial growth factor immunoreaction of the letrozole-treated group showed significant highly positive cytoplasmic reaction. Significant decrease in luteinizing hormone level in the exemestane group and significant increase in the letrozole group were detected. It is concluded that letrozole improved the endometrial thickness and may have a role in ovulation induction. In contrast, exemestane led to disruption of the endometrium and ovary. Therefore, not all aromatase inhibitors help in ovulation