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

Frontiers in Endocrinology 2026 Open access

Read full text
Authors: Viola Viola, Marlene Aguilar, Maria Liza Duremdes Nava, Alessandra Celli, Reina Armamento-Villareal, Yoann Barnouin, NICOLA NAPOLI, Nagireeddy Putluri, Clifford Qualls, Dennis Tan Villareal
DOI: 10.3389/fendo.2025.1719749
Cited by: 1
References: 49

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/m 2 ), hypogonadism (testosterone

Fields of Study & Subjects

Hormonal and reproductive studies Muscle metabolism and nutrition Exercise and Physiological Responses

Publication details

Journal / source
Frontiers in Endocrinology
Publisher
Frontiers Media SA
Volume
16
Pages
1719749–1719749
Publication date
9 February 2026
Language
EN