Background and Objectives: Chemical androgen deprivation and estrogenization are essential components of clinical treatment for advanced prostate cancer and male-to-female sex transition. The aim of this study was to determine the effects of these therapies on anthropometric parameters, liver histology, and biochemical parameters, with the goal of establishing experimental models that accurately represent current clinical practice. Materials and Methods: Young adult Wistar rats were divided into nine groups: intact control (IC), control vehicle (CV), cyproterone acetate-treated (CA), flutamide-treated (F), control sesame oil (CO), estradiol valerate-treated (E), combined control (CC), flutamide + estradiol valerate (F + E), and cyproterone acetate + estradiol valerate (CA + E)-treated groups. Treatments were administered by subcutaneous injection for four weeks. Results: The administration of estradiol valerate, alone or combined with antiandrogens, reduced final body mass and white adipose tissue mass. Notable changes were observed in absolute and relative pituitary, liver, prostate, and testis mass in the E, F + E and CA + E groups. There were no significant changes in liver histology or glycogen deposition; however, the combined treatment groups showed an increased volume density of binucleated hepatocytes and fibrotic tissue. Regarding biochemical parameters, androgen deprivation and/or estrogenization caused marked changes in serum triglyceride, LDL (low-density lipoproteins), ALP (alkaline phosphatase), AST (aspartate aminotransferase), ALT (alanine aminotransferase), Bil-T (bilirubin), creatinine, and urea levels. Conclusions: Given the importance of these therapies in clinical practice, providing a model based on the evaluated parameters offers a solid platform for future research.