Megestrol acetate stimulates weight gain and ventilation in underweight COPD patients

To assess the effect of megestrol acetate (MA), a progestational appetite stimulant commonly used in patients with AIDS and cancer, on body weight and composition, respiratory muscle strength, arterial blood gas levels, and subjective perceptions in COPD patients.

Prospective, double-blind, randomized, placebo-controlled trial conducted on an outpatient basis at 18 sites.

Underweight (< 95% ideal body weight) COPD patients > or = 40 years old.

Either MA, 800 mg/d oral suspension, or placebo at a 1:1 ratio for 8 weeks.

Of 145 randomized patients (63% men), 128 patients completed the trial. Body weight increased by 3.2 kg in the MA group and 0.7 kg in the placebo group (p < 0.001). Anthropometric and dual-energy radiograph absorptiometry assessments confirmed that weight gain was mainly fat. Spirometry and maximal voluntary ventilation showed no significant changes from baseline in either group, and the difference in the change in maximum inspiratory pressure between groups was not significant. The 6-min walk distances did not differ statistically between groups at week 2 and week 4, but were greater in the placebo group at week 8 (p = 0.012). Consistent with the known ability of MA to stimulate ventilation, PaCO(2) decreased (4.6 mm Hg, p < 0.001) and PaO(2) increased (2.8 mm Hg, p < 0.04) in the MA group. Questionnaires revealed that body image and appetite improved in the MA group but not the placebo group. Adverse event frequency and type were similar in both groups, but cortisol and testosterone (in men) levels decreased substantially in the MA group.

We conclude that MA safely increased appetite and body weight, stimulated ventilation, and improved body image in underweight COPD patients, but did not improve respiratory muscle function or exercise tolerance.