EFFECTS OF SUPRAPHYSIOLOGICAL TESTOSTERONE (200 MG/WEEK) DURING SEVERE CALORIC DEFICIT IN YOUNG MEN: BODY COMPOSITION, MUSCLE FUNCTION, NEUROBEHAVIORAL OUTCOMES, AND SAFETY

Background: Severe energy deficit during military operations leads to substantial loss of lean body mass, impaired performance, and adverse psychological outcomes. The administration of supraphysiological testosterone has been proposed as a countermeasure, but an integrated synthesis of its short-term effects on body composition, muscle function, neurobehavioral responses, and safety has not been reported. Methods: We reviewed publications derived from a single randomized, double-blind, placebo-controlled trial conducted in 50 healthy young men (18–39 years) undergoing a 28-day period of ~55% caloric deficit combined with high physical activity, followed by a 14-day ad libitum recovery. Participants received weekly intramuscular injections of testosterone enanthate (200 mg; n=24) or placebo (sesame oil; n=26). Outcomes included body composition, muscle function, muscle protein synthesis and molecular markers, energy metabolism, appetite regulation, hematology and iron metabolism, neuroimaging, and behavioral measures. Safety data were extracted from all reports. Results: Testosterone treatment significantly increased lean body mass (+2.5 to +3.8 kg) compared to placebo, while fat loss was similar between groups. Muscle strength and lower-limb function were not improved, despite gains in lean mass. At the molecular level, testosterone enhanced androgen receptor content, translational capacity, and preserved anabolic proteomic signatures, although muscle protein synthesis rates declined in both groups during the deficit. Energy expenditure and substrate oxidation were unaffected, but nitrogen balance was more favorable. Ghrelin elevation during the deficit was attenuated with testosterone, yet subjective hunger and food intake did not differ. Testosterone reduced hepcidin and increased soluble transferrin receptor levels, supporting enhanced iron availability and erythropoiesis. Functional MRI studies demonstrated altered activation of executive networks and increased self-reported anger during provocation tasks. No serious adverse events occurred; expected suppression of gonadotropins and modest increases in hemoglobin/hematocrit were observed. Conclusions: In young men exposed to severe caloric deficit, supraphysiological testosterone (200 mg/week) preserved lean mass and nitrogen balance and promoted erythropoietic and molecular anabolic adaptations, without improving muscle strength. Short-term safety was acceptable within the controlled setting, though behavioral changes and HPG-axis suppression warrant monitoring