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Randomized Controlled Trial
. 2025 Feb 18;110(3):e814-e826.
doi: 10.1210/clinem/dgae249.

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

Adrian M Gonzalez-Gil  1   2 , Yoann Barnouin  1   2 , Alessandra Celli  1   2 , Viola Viola  1   2 , Marcos D Villarreal  1   2 , Maria Liza Duremdes Nava  1   2 , Adam Sciuk  3 , Clifford Qualls  4 , Reina Armamento-Villareal  1   2 , Dennis T Villareal  1   2
Affiliations
Randomized Controlled Trial

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

Adrian M Gonzalez-Gil et al. J Clin Endocrinol Metab. .

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: aging; hypogonadism; lifestyle therapy; obesity; testosterone.

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Conflict of interest statement

DECLARATION OF INTERESTS

The authors declare no conflicts of interest.

No commercial support was received.

References

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