Effects of muscle strength training and megestrol acetate on strength, muscle mass, and function in frail older people.

OBJECTIVES To determine the independent and combined effects of progressive resistance muscle strength training (PRMST) and megestrol acetate (MA) on strength, muscle mass, and function in older recuperative care patients. DESIGN Double-blind, randomized, controlled intervention using a two-by-two factorial design and conducted between 1999 and 2001. SETTING University-affiliated Department of Veterans Affairs hospital. PARTICIPANTS Twenty-nine patients (mean age 79.4 +/- 7.4, 90% white) aged 65 and older and had recent functional decline. INTERVENTIONS After randomization to one of four treatment groups (low-resistance exercises plus 800 mg per day of MA or a placebo or high-intensity PRMST plus 800 mg/d of MA or placebo), subjects received training and the drug or placebo for 12 weeks. MEASUREMENTS Change in muscle strength, mid-thigh muscle area, and aggregate functional performance score as assessed using analysis of covariance. RESULTS Five subjects withdrew from the study before its completion. Based on intent-to-treat analyses, subjects who received high-intensity PRMST and placebo experienced the greatest strength gains. The addition of MA was associated with worse outcomes than with high-intensity exercise training alone, especially with regard to the leg exercises. Post hoc analysis demonstrated that subjects who received high-intensity PRMST and placebo experienced significantly greater percentage increases in leg strength than subjects in either of the MA treatment groups (P<.05 for each comparison). There was also a significant negative effect of MA on physical function. In general, subjects who received MA experienced a deterioration in aggregate physical function scores, whereas the remaining subjects improved (-0.80+/-0.40 vs 0.48+/-0.41, P=.04). There was not a significant interaction between exercise and MA for any outcome. CONCLUSION High-intensity PRMST is a safe and well-tolerated exercise regimen for frail elderly patients. The addition of MA appears to blunt the beneficial effects of PRMST, resulting in less muscle strength and functional performance gains.