Journal Article

Metabolic Effects of Testosterone Added to Intensive Lifestyle Intervention in Older Men With Obesity and Hypogonadism

Villarreal, Marcos D, Viola, Viola, Duremdes Nava, Maria Liza, Armamento-Villareal, Reina, Celli, Alessandra, Sciuk, Adam, Gonzalez-Gil, Adrian M, Barnouin, Yoann, Qualls, Clifford, Villareal, Dennis T

2025

Overview

Whether testosterone replacement therapy (TRT) conveys additional cardiometabolic benefit to an intensive lifestyle therapy (LT) in older men with obesity and hypogonadism remains unclear. To determine whether TRT augments the effect of LT on metabolic outcomes in older men with obesity and hypogonadism. Secondary analysis of a randomized, double-blind, placebo-controlled trial. Veterans Affairs Medical Center. Eighty-three older (age ≥ 65 years) men with obesity (body mass index ≥ 30 kg/m2) and persistently low Am testosterone (< 10.4 nmol/L) associated with frailty. LT (weight management and exercise training) plus either testosterone (LT + TRT) or placebo (LT + Pbo) for 6 months. The primary outcome was change in glycated hemoglobin (HbA1c). Secondary outcomes included changes in other glucometabolic and lipid profile components, liver enzymes, inflammatory markers, and adipokines; subcutaneous, visceral, intramuscular, and hepatic fat; blood pressure; and metabolic syndrome score. HbA1c decreased similarly in LT + TRT and LT + Pbo groups (-0.5 ± 0.1 vs -0.6 ± 0.1%, respectively; P = 0.35). While TRT showed no synergistic effect with LT on ameliorating secondary outcomes, it eliminated the augmentative effect of LT on high-density lipoprotein cholesterol concentration (5.4 ± 1.0 mg/dL in the LT + Pbo group vs 0.2 ± 1.1 mg/dL in the LT + TRT group, P = .01) and adiponectin levels (-408 ± 489 ng/mL in LT + TRT group vs 1832 ± 468 ng/mL in LT + Pbo group, P = .02). In older men with obesity and hypogonadism, adding TRT for 6 months to LT does not result in further improved cardiometabolic profiles and could potentially blunt some of the metabolic benefits induced by LT.

• Publisher: Oxford University Press
• Subject: Aged / Aged, 80 and over / Body mass index / Combined Modality Therapy / Double-Blind Method / Enzymes / Exercise Therapy / Glycated Hemoglobin - analysis / Glycosylated hemoglobin / Hormone Replacement Therapy - methods / Humans / Hypogonadism / Hypogonadism - complications / Hypogonadism - drug therapy / Hypogonadism - metabolism / Hypogonadism - therapy / Life Style / Liver / Male / Medical centers / Obesity / Obesity - complications / Obesity - metabolism / Obesity - therapy / Testosterone / Testosterone - administration & dosage / Testosterone - therapeutic use / Treatment Outcome / Type 2 diabetes