Metabolic Effects of Testosterone Replacement Therapy in Men with Functional Secondary Hypogonadism, Obesity and Type 2 Diabetes or Metabolic Syndrome: A Systematic Review
- Journal
- Medical sciences (Basel, Switzerland) (Q1)
- Published
- 22 July 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Christos Ntais, Apostolos Vantarakis, Ioanna P Chatziprodromidou
- PMID
- 42506387
- DOI
- 10.3390/medsci14030418
Why clinicians should know about it
- Picked for Biochemistry (medical) (top studies of the week, 2 August 2026).
Abstract
BACKGROUND/OBJECTIVES: Functional secondary hypogonadism is frequent in men with obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM), but whether testosterone replacement therapy (TRT) produces clinically relevant metabolic benefits remains uncertain. This systematic review evaluated double-blind randomized placebo-controlled trials of TRT in obese men with functional secondary hypogonadism and either T2DM or metabolic syndrome. METHODS: PubMed and Scopus were searched up to May 2026. Eligible studies enrolled adult men with biochemical hypogonadism and T2DM or metabolic syndrome, compared TRT with placebo, and reported metabolic outcomes. Open-label, single-blind, and non-randomized studies were excluded. Risk of bias was assessed with the Cochrane RoB 2 framework and certainty of evidence with GRADE. RESULTS: Eight trials were included. The most consistent signal was improvement in body composition, mainly increased lean mass and reduced fat mass. Effects on insulin resistance were favorable in several trials but heterogeneous. GRADE certainty was low for fat mass, lean mass, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and it was very low for clamp-derived insulin sensitivity, HbA1c, fasting glucose, lipid outcomes, inflammatory and vascular surrogate markers, and long-term safety. CONCLUSIONS: Low-certainty evidence suggests that TRT may improve body composition and HOMA-IR in carefully selected men with functional secondary hypogonadism and metabolic disease, whereas effects on glycemic and lipid outcomes remain very uncertain. TRT should not be regarded as an antidiabetic or lipid-lowering intervention. Larger phenotype-specific trials with longer follow-up are needed.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.