Abstract
The purpose of this study was to investigate the impact of conjugated estrogen cream, in conjunction with progesterone, on the endometrium, following vaginal administration, and assess the combined dose-effect relationship with progesterone. Initially, bilateral ovaries from mature, female, Sprague Dawley rats were excised to establish a hypoestrogenic (perimenopausal) model. A conjugated estrogen-progesterone combination cream was administered vaginally for a duration of 12 days. Subsequently, this study used pathological sections, Enzyme-Linked Immunosorbent Assay (ELISA) for pharmacodynamic studies, network pharmacology to explore possible signalling pathways associated with the drug and menopausal syndrome, and partial validation using a real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (ICH). The results demonstrate that, relative to the model group, the conjugated estrogen monotherapy significantly increased the uterine weight coefficients (p < 0.0001) and endometrial thickness (p < 0.001) and upregulated the expression of Cyclin D1 and VEGF. Moreover, this treatment downregulated PTEN expression. The co-administration of progesterone reversed these effects in a dose-dependent manner. Overall, the vaginal administration of a combination of progesterone and conjugated estrogen cream demonstrated the ability to mitigate endometrial hyperplasia induced by conjugated estrogen vaginal cream monotherapy. Furthermore, the effect of progesterone exhibited a dose-dependent response.