Testosterone Treatment and Sexual Function in Men: Secondary Analysis of the T4DM (Testosterone for Diabetes) Trial

Gary A Wittert; Kristy P Robledo; David J Handelsman; Warrick J Inder; Bronwyn G A Stuckey; Bu B Yeap; Karen Bracken; Carolyn A Allan; David Jesudason; Alicia Jenkins; Andrzej S Januszewski; Mathis Grossmann

doi:10.1210/clinem/dgaf060

Testosterone Treatment and Sexual Function in Men: Secondary Analysis of the T4DM (Testosterone for Diabetes) Trial

J Clin Endocrinol Metab. 2025 Feb 10:dgaf060. doi: 10.1210/clinem/dgaf060. Online ahead of print.

Authors

Affiliations

¹ Freemasons Foundation Centre for Men's Health, University of Adelaide, Adelaide, South Australia, Australia, and The Queen Elizabeth Hospital, South Australia, Australia.
² NHMRC Clinical Trials Centre, University of Sydney, New South Wales, Australia.
³ ANZAC Research Institute, University of Sydney and Department of Andrology, Concord Hospital, Sydney New South Wales, Australia.
⁴ Princess Alexandra Hospital and the University of Queensland, Queensland, Australia.
⁵ Keogh Institute for Medical Research, Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital and Medical School, University of Western Australia, Western Australia, Australia.
⁶ Medical School, University of Western Australia and Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Western Australia, Australia.
⁷ Sydney Musculoskeletal Health, Faculty of Medicine and Health, The University of Sydney.
⁸ Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, School of Clinical Sciences at Monash Health, and Faculty of Medicine, Nursing and Health Sciences, Monash University.
⁹ Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
¹⁰ Sydney School of Pharmacy, Faculty of Medicine and Health, The University of Sydney.
¹¹ Department of Medicine and Endocrinology, Austin Health, Heidelberg and University of Melbourne, Victoria, Australia.

PMID: 39928571
DOI: 10.1210/clinem/dgaf060

Abstract

Context: The combined effects of testosterone treatment and lifestyle intervention on sexual function in men at high risk of type 2 diabetes are unclear.

Objective: To assess the effect of testosterone treatment with a lifestyle intervention in men aged 50-74 years at high risk of, or newly diagnosed with, type 2 diabetes (OGTT).

Design: A secondary analysis of the Testosterone for the Prevention of Type 2 Diabetes (T4DM) trial, a double-blind, placebo-controlled trial conducted across six Australian centers.

Interventions: Intramuscular testosterone undecanoate (1000 mg) or placebo, 3 monthly for 2 years alongside a community-based lifestyle program.

Main outcomes: Sexual function measured using the International Index of Erectile Function (IIEF)-15 questionnaire.

Results: Of 1007 participants, 792 (79%) had complete IIEF-15 data. Baseline domain scores were inversely related to age and waist circumference, but unrelated to serum testosterone or estradiol levels. Testosterone treatment improved all five IIEF-15 domain scores, with stronger effects on sexual desire and orgasmic function in older men, and sexual desire in men with higher depression scores. Testosterone had no impact on depression. Independent of treatment, reductions in waist circumference were associated with improved erectile function, and reductions in depression scores correlated with better sexual function. Clinically significant improvement (CSI) in erectile function and sexual desire occurred in 3% and 10% of men, respectively, and was inversely related to baseline function. CSI improvements in erectile function and sexual desire were greater in younger and older men respectively.

Conclusion: Testosterone treatment enhanced sexual desire and, to a lesser extent, erectile function, particularly in older men and those with higher waist circumference or depressive symptoms. Reduced waist circumference and depression independently improved sexual function.

Keywords: Testosterone; clinical trial; diabetes; obesity; sexual function.