A randomized pilot study of monthly cycled testosterone replacement or continuous testosterone replacement versus placebo in older men

Context: Cycling androgens has been reported by athletes to improve physical performance by enhancing muscle mass and strength, a paradigm that has not been studied, and may have clinical value in older men being treated with testosterone. Objective: We investigated the efficacy of a monthly cycled testosterone regimen that uses half the testosterone dose as the current standard of care continuous therapy on body composition and muscle strength in older men. Design, Setting, and Patients: Twenty-four community-dwelling older men 70 ± 2 yr of age with total testosterone levels below 500 ng/dl were randomized at the Institute for Translational Sciences- Clinical Research Center into a 5-month double-blind placebo-controlled trial. Intervention: Subjects were dosed weekly for 5 months, receiving continuous testosterone (TE, n = 8; 100 mg testosterone enanthate, im injection), monthly cycled testosterone (MO, n = 8; alternating months of testosterone and placebo), or placebo (PL, n = 8). Main Outcome Measures: Main outcomes included body composition by dual-energy x-ray absorptiometry and upper and lower body muscle strength. Secondary outcomes included body weight, serum hormones, and mixed-muscle protein fractional synthesis rate (FSR). Results: Total lean body mass was increased and percent fat was reduced after 5 months in TE and MO (P < 0.05). Upper body muscle strength increased in TE, and lower body muscle strength increased in TE and MO (P < 0.05). FSR increased in TE and MO (P < 0.05) but not in PL. Conclusions: Cycled testosterone improved body composition and increased muscle strength compared with placebo and increased FSR similarly to continuous testosterone.