Testosterone and anabolic therapy to recover strength, function, and quality of life after critical illness

Critical illness induces profound catabolic stress characterized by accelerated skeletal muscle breakdown, hypermetabolism, persistent catabolism including testosterone deficiency, and rapid functional decline. Loss of skeletal muscle contributes to prolonged hospitalization, ICU-acquired weakness, delayed recovery, and persistent disability in ICU survivors. This review summarizes recent evidence on anabolic therapies - including testosterone, oxandrolone/nandrolone, creatine, and β-hydroxy-β-methylbutyrate (HMB) - that may mitigate muscle wasting and improve functional recovery after critical illness.

Many ICU patients develop marked testosterone deficiency early during critical illness, which may contribute to persistent catabolism and impaired recovery. Oxandrolone has the strongest clinical evidence, particularly in burn injury. Emerging outcome and improved safety data suggest testosterone may improve strength and functional recovery, particularly in patients with low testosterone levels. Nandrolone is being evaluated in a randomized trial for ICU-acquired weakness. Nutritional supplements such as creatine and HMB can improve lean mass and strength, especially when combined with structured exercise.

Anabolic therapies appear most effective when integrated into multimodal recovery strategies combining personalized nutrition, progressive rehabilitation, and targeted pharmacologic support. Multidisciplinary prehabilitation/rehabilitation services/clinics may help accelerate recovery and reduce long-term disability in ICU survivors, though further multicomponent trials, including anabolic agents are urgently needed.