Testosterone plus lifestyle therapy improves skeletal muscle glycolysis in older men with obesity and hypogonadism.

ABSTRACT:

Objective

Weight loss in older men with obesity and hypogonadism accelerates musculoskeletal decline, yet the underlying metabolic mechanisms remain unclear. Testosterone replacement therapy (TRT), when added to lifestyle therapy (LT), mitigates this decline, but its metabolic basis has not been defined. We examined skeletal muscle metabolomic adaptations to LT with or without TRT, focusing on glycolysis, the pentose phosphate pathway (PPP), the tricarboxylic acid (TCA) cycle, and carnitine metabolism to identify dominant pathways of metabolic adaptation.

Design

Randomized, double-blind, placebo-controlled trial (LITROS).

Methods

Eighty-three men aged 65 years or older with obesity (BMI ≥30 kg/m²), hypogonadism (testosterone <10.4 nmol/L), and frailty (Phys

SUBMITTER: Viola V 

PROVIDER: S-EPMC12914099 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature