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

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

Journal: The Journal of clinical endocrinology and metabolism 2025;110(7):e2157-e2170

PMID: 39928571

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Plain Language Summary

This study examined how testosterone treatment affects sexual function in men aged 50 to 74 years who are at high risk of or newly diagnosed with type 2 diabetes. .

The results showed that testosterone treatment improved sexual function compared to placebo, with the strongest effects seen on sexual desire and orgasmic function. These benefits were more pronounced in older men, and the improvement in sexual desire was greater in men who had higher depression scores at the start of the study. Notably, testosterone treatment itself did not affect depression scores. Separately from treatment, men who reduced their waist circumference over the study period showed improved erectile function, and those with improved depression scores also showed better sexual function. However, the proportion of men achieving a clinically meaningful improvement was modest: only 3% saw a clinically significant improvement in erectile function, and 10% in sexual desire.

In conclusion, testosterone treatment may improve sexual desire and, to a lesser extent, erectile function in men with or at risk of type 2 diabetes, with the greatest benefit seen in older men and those with higher depressive symptoms or larger waist circumference. However, testosterone did not improve depression itself, and the proportion of men experiencing clinically significant improvement was relatively small. This study could be used by healthcare professionals to understand the effects of testosterone treatment on sexual function in men at risk of type 2 diabetes

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 to 74 years at high risk of, or newly diagnosed with, type 2 diabetes (via oral glucose tolerance test).

DESIGN

A secondary analysis of the Testosterone for the Prevention of Type 2 Diabetes trial, a double-blind, placebo-controlled trial conducted across 6 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 International Index of Erectile Function-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 5 International Index of Erectile Function-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 in erectile function and sexual desire occurred in 3% and 10% of men, respectively, and was inversely related to baseline function. Clinically significant improvement 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.

Address: Freemasons Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, SA 5000, Australia.; Department of Endocrinology, The Queen Elizabeth Hospital, Woodville, Adelaide, SA 5011, Australia.; NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW 2050, Australia.; ANZAC Research Institute, University of Sydney and Department of Andrology, Concord Hospital, Sydney, NSW 2139, Australia.; Department of Endocrinology, Princess Alexandra Hospital and the University of Queensland, Brisbane, QLD 4102, Australia.; Keogh Institute for Medical Research, Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital and Medical School, University of Western Australia, Nedlands, WA 6009, Australia.; Medical School, University of Western Australia and Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, WA 6150, Australia.; Sydney Musculoskeletal Health, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia.; 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, Clayton, VIC 3168, Australia.; Diabetes and Vascular Medicine, Baker Heart and Diabetes Institute, Melbourne, Melbourne, VIC 3074, Australia.; Sydney School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Canperdown, NSW 2050, Australia.; Department of Medicine and Endocrinology, Austin Health, and University of Melbourne, Heidelberg, VIC 3079, Australia.

DOI: 10.1210/clinem/dgaf060

Patient Centred Factor

Mediators

Physical Environment

Psychosocial influences

Clinical Imbalances

Hormonal Blood Sugar Regulation and Insulin Sensitivity

Laboratory Testing

Blood

Modifiable Lifestyle Factors

Diet Psychological Nutrients/ Supplements

Jadad Score

Allocation Concealment

Yes

Nutrition Evidence Keywords

Lifestyle intervention Cardiometabolic Type 2 diabetes

Bioactive Substances

Testosterone

Link outs

Free resources

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https://pmc.ncbi.nlm.nih.gov/articles/pmid/3992857...

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MeSH Terms: Humans, Male, Testosterone, Middle Aged, Aged, Diabetes Mellitus, Type 2, Double-Blind Method, Erectile Dysfunction, Sexual Behavior, Australia, Penile Erection, Treatment Outcome, Life Style, Androgens, Libido