Megestrol acetate significantly decreases the circulating concentrations of estradiol (E2) and testosterone (T) in female fish or 11-ketotestosterone (11-KT) in male fish. Megestrol acetate exposure significantly downregulates the transcription of certain genes along the hypothalamic-pituitary-gonadal (HPG) axis.  Megestrol acetate produces a progressive deterioration in glucose tolerance, with a significant increase in mean fasting plasma glucose concentrations and decrease in mean plasma glucose clearance rates after 6 months and 12 months of treatment in cats. Megestrol acetate also produces a progressive decrease in both resting plasma cortisol concentrations and cortisol concentrations after ACTH stimulation in cats.  Megestrol acetate (50 mg/kg/day) for 9 days significantly increases food and water intake compared with untreated controls. Megestrol acetate (50 mg/kg/day) significantly (90-140%) increases in neuropeptide Y concentrations in the arcuate nucleus (where neuropeptide Y is synthesized), in the lateral hypothalamic area (through which arcuate neurones project) and in the medial preoptic area, ventromedial nucleus and dorsomedial nucleus in rats.