Oral Presentation ESA-SRB 2023 in conjunction with ENSA

Testosterone treatment in eugonadal men discloses a differential association between decreased adiposity and changes in testis volume compared to placebo. (#99)

Warrick J Inder 1 2 , Kristy P Robledo 3 , Carolyn A Allan 4 , Karen Bracken 3 , Ann J Conway 5 , Mathis Grossmann 6 7 , Alicia Jenkins 8 , David Jesudason 9 10 , Robert McLachlan 4 , Bronwyn GA Stuckey 11 12 , Bu B Yeap 12 13 , David J Handelsman 5 , Gary A Wittert 9 14
  1. Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, QLD, Australia
  2. Medical School, The University of Queensland, Herston, QLD, Australia
  3. NHMRC Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia
  4. Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, VIC, Australia
  5. ANZAC Research Institute, Concord Hospital, University of Sydney, Concord, NSW, Australia
  6. Endocrinology, Austin Hospital, Heidelberg, VIC, Australia
  7. Medicine, University of Melbourne, Parkville, VIC, Australia
  8. Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
  9. School of Medicine, University of Adelaide, Adelaide, SA, Australia
  10. Endocrinology, The Queen Elizabeth Hospital, Woodville South, SA, Australia
  11. Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
  12. Medical School, University of Western Australia, Perth, WA, Australia
  13. Endocrinology and Diabetes, Fiona Stanley Hospital, Murdoch, WA, Australia
  14. Freemasons Centre for Male Health and Wellbeing, South Australian Health Medical Research Institute, Adelaide, SA, Australia

Reduced testis volume in eugonadal men treated with testosterone is well-recognised. This sub-study of the Testosterone for the Prevention of Type 2 Diabetes (T4DM) Trial investigated i) baseline determinants of testis volume, ii) changes in testis volume over 2 years following randomisation to testosterone or placebo, and iii) the effect of changes in fat mass (DXA), BMI, and waist circumference (WC) on testis volume.

T4DM enrolled men aged 50-74 years, with impaired glucose tolerance or early type 2 diabetes, WC ≥95cm, serum testosterone ≤14 nmol/L and without pathological hypogonadism. All were enrolled in Weight-Watchers (WW) and randomised to 2 years treatment with testosterone undecanoate (1000 mg IM 3 monthly) or matching placebo. At one study centre, a single investigator (WJI) measured testis volume (Prader orchidometer) at baseline and final visits while blinded to treatment assignment.

The sub-study participants (n=123, 63 testosterone 60 placebo) were similar in age to the whole T4DM cohort but had higher weight (p=0.036), waist circumference (p=0.005), and BMI-graded obesity (p=0.004). Baseline testis volume was 19.4±4 ml and was inversely correlated with serum FSH (p=0.001) and LH (p=0.004), but not adiposity measures.

At 2 years, testis volume of testosterone-treated men was reduced by 5.9 ml (95% CI 4.6-7.2) more than placebo recipients (p<0.001), while the changes in BMI (Testosterone -1.7±2.3 kg/m2 v Placebo -1.7±2.7 kg/m2), fat mass (Testosterone -4.3±5.7 kg v Placebo -2.1±7.3 kg) and WC (Testosterone -6.8±5.7 cm v Placebo -4.8±7.3 cm) were not significantly different. However, reduced adiposity was associated with lower testis volume in testosterone-treated men, but with higher testis volume in placebo-treated men (treatment x fat mass interaction p-int=0.012; treatment x WC, p-int=0.01).

Two years of testosterone treatment in men with dysglycaemia reduced testis volume and was associated with decreased adiposity. However, in placebo-treated men, reduced adiposity was associated with increased testis volume.