The largest investigation of testosterone treatment ever undertaken has shown that, over and above the effect of a lifestyle program, treatment with testosterone prevents or reverses newly diagnosed type 2 diabetes in men.

The study, known as T4DM (Testosterone for the prevention of Diabetes Mellitus), was led Professor Gary Wittert, Endocrinologist and Director of the Freemasons Foundation Centre for Men’s Health -University of Adelaide and involved six specialist centres across Australia. T4DM was a two-year randomised, double-blind, placebo-controlled clinical trial and has been published in the leading Journal The Lancet Diabetes & Endocrinology .

The T4DM study included more than 1000 men aged between 50 and 74 years old who were overweight or obese. All men were enrolled in the WW (formerly known as Weight Watchers) lifestyle program. They could attend groups, use the website, the app, or any combination of those. Half of the men were injected with long-acting testosterone every three months and the other half were injected with placebo.

After two years of treatment, 87 out of 413 (21%) men in the placebo group had type 2 diabetes (based on an oral glucose tolerance test) compared with 55 out of 443 (12%) men in the testosterone group.

Men in both groups lost weight (on average 3 to 4kg) and glucose tolerance normalised in 43% and 52% of men in the placebo and testosterone groups, respectively.

The results of the study show that, on top of modest weight loss achieved with healthy eating and increased activity, testosterone has some added benefit to prevent or reverse newly diagnosed type 2 diabetes

Other findings at two years in men treated with testosterone compared to placebo:

A lower fasting blood sugar
A greater decrease in body fat
An increase in skeletal muscle mass and hand grip strength
Improvements in sexual function
There were no differences in wellbeing or quality of life.

The most common adverse effect occurring in 22% of men treated with testosterone was an increase in the concentration of red cells in the blood, which could potentially lead to “sludgy” blood.

Lead researcher Professor Gary Wittert, Director of the Freemason’s Centre for Male Health and Wellbeing, University of Adelaide, said: “The results of the study show that, on top of modest weight loss achieved with healthy eating and increased activity, testosterone has some added benefit to prevent or reverse newly diagnosed type 2 diabetes.

Writing a prescription might be quick and easy but it does not replace the need for undertaking a comprehensive assessment and providing holistic management towards improving men’s health.

The results do not necessarily mean that a script for testosterone should be written. Men at risk of type 2 diabetes are usually overweight and either have, or are at risk of, other chronic disorders that have not been detected or adequately managed. Not infrequently these men are also drinking too much alcohol and have sleep or mood disorders. Weight loss achieved through healthy lifestyle behaviours remains the benchmark.

More research is needed to determine whether the beneficial effects of testosterone persist beyond two years, whether longer term treatment is safe and whether other forms of testosterone have similar benefits or risks.

Four sub-studies are underway:

Sub-study 1: Effects of testosterone treatment on bone micro-architecture and density (T4Bone)

The first results published from this sub-study has shown that testosterone treatment for 2 years increased volumetric bone density, predominantly via effects on cortical bone. Implications for fracture risk reduction requires further study. Read abstract

Sub-study 2: Effects of testosterone treatment on motivation and behaviour (T4M&B)
Sub-study 3: Effects of testosterone treatment on telomere length (T4Telomeres)
Sub-study 4: Effects of extended testosterone treatment for up to 4 years and rate of HPT axis recovery at the end of treatment.

Professor Bu Yeap from the University of Western Australia’s Medical School, and President of the Endocrine Society of Australia, who was an investigator on the study, said: “This is a landmark study which will prompt renewed interest in preventing diabetes in at-risk men.”

The study was funded by the National Health and Medical Research Council of Australia, Bayer, Eli Lilly, WW and the Freemasons Centre for Male Health & Wellbeing - University of Adelaide .

The paper in The Lancet Diabetes & Endocrinology can be found online here: http://www.thelancet.com/journals/landia/article/PIIS2213-8587(20)30367…

For a full lay summary go to: https://ctc.usyd.edu.au/media/5748/t4dm-summary-of-outcomes-final-300620.pdf

The other T4DM program Investigators include A/Prof Evan Atlantis (Western Sydney Uni, NSW), Dr Carolyn Allan, Prof Robert McLachlan (Hudson Institute of Medical Research, VIC), Dr Karen Bracken, Dr Alicia Jenkins (Uni of Sydney), Prof Ann Conway and Prof David Handelsman (Anzac Institute, NSW), Prof Mark Daniel (Uni of Canberra), Prof Mathis Grossmann (Uni of Melbourne, VIC), Prof Bronwyn Stuckey and Prof Bu Yeap (Uni of WA), and Dr David Jesudason (Queen Elizabeth Hospital)