Effects of megestrol acetate on glucose tolerance and growth hormone secretion in the cat

Long-term administration of relatively high therapeutic dosages of megestrol acetate to cats produced a progressive deterioration in glucose tolerance, with a significant (P less than 0.05) increase in mean fasting plasma glucose concentrations and decrease in mean plasma glucose clearance rates after six and 12 months of treatment. There appeared to be no relationship, however, between the development of glucose intolerance and circulating growth hormone (GH) concentrations in the cats of this study, since no significant rise in plasma GH concentrations was detected during the 12 month period of megestrol acetate treatment. Administration of megestrol acetate also produced a progressive decrease in both resting plasma cortisol concentrations and cortisol concentrations after ACTH stimulation. Three months after discontinuation of megestrol acetate, the elevated fasting plasma glucose concentrations, decreased glucose clearance rates and subnormal plasma cortisol concentrations all returned to normal pretreatment values, indicating resolution of glucose intolerance and hypoadrenocorticism. The results of this study demonstrate that administration of megestrol acetate to cats can produce a state of moderate to severe glucose intolerance, which is usually reversible after cessation of treatment. Although the exact mechanism of the glucose intolerance and overt diabetes mellitus induced by progestagen treatment of cats remains unclear, it is likely that these alterations in glucose metabolism result primarily from the glucocorticoid activity intrinsic to megestrol acetate.