Oral Presentation ESA-SRB-ANZOS 2025 in conjunction with ENSA

Effect of testosterone treatment on leucocyte telomere length in men at high risk for type 2 diabetes mellitus. (128000)

Bu B Yeap 1 2 , Jennie Hui 3 , Kristy P Robledo 4 , Gillian Arscott 3 , Mathis Grossmann 5 , David J Handelsman 6 , Warrick J Inder 7 , Bronwyn GA Stuckey 8 , Alicia J Jenkins 9 , Karen Bracken 4 , John P Beilby 10 , Gary A Wittert 11
  1. Medical School, University of Western Australia, Perth, WA, Australia
  2. Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, WA, Australia
  3. PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia
  4. NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia
  5. Department of Medicine (Austin Health), University of Melbourne, Melbourne, VIC, Australia
  6. ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia
  7. Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, QLD, Australia
  8. Keogh Institute of Medical Research, Perth, WA, Australia
  9. Baker Heart and Diabetes Research Institute, Melbourne, VIC, Australia
  10. School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia
  11. Freemasons Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, SA, Australia

Aims

Lower testosterone concentrations in older men are associated with poorer health outcomes, but underlying mechanisms, including possible links to the ageing process, remain unclear. We tested the hypothesis that testosterone treatment modulates leucocyte telomere length, a postulated marker of biological ageing, in overweight men with elevated blood glucose concentrations.

Methods

This was a pre-specified secondary analysis of Testosterone for the Prevention of Type 2 Diabetes Mellitus (T4DM), a randomised, placebo-controlled trial in 50-74-year-old men with waist circumference ≥95 cm and impaired glucose tolerance or newly diagnosed type 2 diabetes mellitus. Men received intramuscular testosterone undecanoate (1000 mg) every three months, or placebo, for two years with a background lifestyle program. Whole blood samples were collected at baseline and two years, and stored frozen at -80oC until retrieval for extraction of DNA and measurement of telomere length. Leucocyte telomere length was assayed by multiplex quantitative polymerase chain reaction and expressed as relative telomere length (rTL), a ratio of telomeric DNA to β-globin, a single-copy control gene (T/S ratio).

Results

Participants were 60±6 years-old (mean±SD), 38% had BMI 30-34.99 kg/m2 and 44% ≥35 kg/m2. Mean rTL at baseline was 1.63±0.27 in testosterone-treated men (N=375) and 1.61±0.28 in placebo-treated men (N=345). At two years, mean rTL were 1.61±0.28 and 1.58±0.29, respectively. Change in rTL after 2 years treatment was -0.02±0.15 in testosterone-treated, and -0.03±0.12 in placebo-treated men. Adjusting for baseline values there was no effect of testosterone treatment on rTL at two years (mean difference 0.01 [95% CI, -0.01 to 0.03], P=0.24). Results were similar for rTL change at two years from baseline.

Conclusion

These rTL results in overweight middle-aged to older men do not support the hypothesis that testosterone modulates biological ageing. Larger studies with longer treatment durations might provide further information.