This study aimed to determine whether hormonal hypersecretion could cause morphological problems in the mouse vagina and affect the ovaries and nearby extra uterine organs. All mice were synchronized to estrus before the experiment. Then human chorionic gonadotropin (hCG), progesterone, and testosterone were continuously administered for about 6 days to maintain hormone hypersecretion, and then morphological changes were analyzed, and Matrix metalloproteinases (MMPs) activity and Casp-3 expression were evaluated. As a result of the analysis, in the case of hCG, the morphological change did not show a significant difference from the vagina of normal estrus. In the case of progesterone, changes were observed in the mucosa zone and basal membrane, and it was confirmed that the activity of MMPs was increased in squamous epithelium cells. On the other hand, in the case of testosterone, overall changes in vaginal tissues were observed, and MMPs activity was increased to a very high level in all sections. The expression of Casp-3 was also the highest compared to other groups. Therefore, as a result of this study, it is thought that hormone hypersecretion affects the morphological changes of the vagina other than the ovaries and uterus and induces the activity of MMPs to cause morphological degeneration of tissues.