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.