Language

English

Publication Date

2-18-2025

Journal

The Journal of Clinical Endocrinology and Metabolism

DOI

10.1210/clinem/dgae249

PMID

38606934

PMCID

PMC11470114

PubMedCentral® Posted Date

2-18-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Background: Whether testosterone replacement therapy (TRT) conveys additional cardiometabolic benefit to an intensive lifestyle therapy (LT) in older men with obesity and hypogonadism remains unclear.

Objective: To determine whether TRT augments the effect of LT on metabolic outcomes in older men with obesity and hypogonadism.

Design: Secondary analysis of a randomized, double-blind, placebo-controlled trial.

Setting: Veterans Affairs Medical Center.

Participants: 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.

Interventions: LT (weight management and exercise training) plus either testosterone (LT + TRT) or placebo (LT + Pbo) for 6 months.

Outcome measures: 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.

Results: 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).

Conclusion: 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.

Keywords

Humans, Male, Testosterone, Hypogonadism, Aged, Obesity, Double-Blind Method, Hormone Replacement Therapy, Life Style, Glycated Hemoglobin, Exercise Therapy, Combined Modality Therapy, Aged, 80 and over, Treatment Outcome, testosterone, lifestyle therapy, aging, obesity, hypogonadism

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