Effect of megestrol acetate on weight loss induced by tumour necrosis factor alpha and a cachexia-inducing tumour (MAC16) in NMRI mice

The effect of the synthetic progesterone, megestrol acetate, on weight loss induced by both tumour necrosis factor alpha (TNF) as a model for the cachexia accompanying the acquired immunodeficiency syndrome and by a cachexia-inducing tumour (MAC16) has been studied in NMRI mice. Megestrol acetate was effective in preventing weight loss in both model systems with treated animals having an increase in intake of both food and water. Megestrol acetate was unable to prevent loss of body weight in animals pair-fed with TNF treated animals, suggesting that the increase in food and water intake was responsible for the increase in body weight. Analysis of body composition showed that the major contribution to the increase in body weight in animals treated with megestrol acetate was an increase in water content, although there was also an increase in carcass fat in animals bearing the MAC16 tumour given the high dose of megestrol acetate. Animals bearing the MAC16 tumour had a significant increase in tumour weight after treatment with megestrol acetate, possibly owing to the increased plasma glucose levels. These results suggest that an increase in appetite and weight gain alone are not sufficient to justify the anticachectic effect of a particular agent and that body composition analysis and tumour growth rate are very important parameters.