Progesterone improves survival in hepatoma cachexia rat model

Abstract

Abstract Background Medroxyprogesterone and megestrol acetate are synthetic progesterone derivatives. Progestagen is an approved drug for cancer cachexia in the USA and in some European countries. These agents have been described to increase appetite and to lead to weight gain. However, the effects on survival are still unknown. The aim of this study was to evaluate the effects of progesterone on survival, cardiac function, and appetite and body weight in the Yoshida hepatoma AH‐130 rat cancer cachexia model. Methods and Results In this study, the effects of progesterone were tested in cachectic tumour‐bearing rats. Rats were treated with 0.5, 5 or 50 mg/kg/day, respectively, or placebo daily, starting 1 day after tumour inoculation for a period of 16 days. Cardiac function was analysed by echocardiography at baseline and at day 11. Food intake was assessed before tumour inoculation and at day 11. Body weight and body composition were evaluated at the beginning and the end of study or the day of euthanasia. Survival was significantly improved by 5 mg/kg/day (hazard ratio: 0.48, 95% confidence interval: 0.24–0.95, P = 0.0356). However, there was no significant difference between the progesterone treatment groups compared with placebo in body weight change and body composition, as well as food intake on day 11. Cardiac function also showed no significant difference compared with placebo. Conclusions Progesterone improves survival but has no beneficial effects on cardiac function, body weight, and food intake in this aggressive hepatoma cancer cachexia rat model. Further studies are needed to elucidate the mechanism of the survival benefit.

Keywords

• Progesterone
• Appetite
• Body weight