We are conducting studies of testosterone therapy in middle-aged and older men with an emphasis on its effects on visceral adiposity and markers of cardiovascular risk.
1. Testosterone Replacement Therapy in obese men
We completed a study of the efficacy and safety of testosterone replacement therapy in 40 middle-aged and older men with an emphasis on its effects on visceral adiposity and markers of cardiovascular risk. We are continuing to analyse the data from this study.
In 2010 we conducted a major clinical study of the efficacy and safety of testosterone replacement in ageing obese men. Conducted under the auspices of the Monash Health Human Ethics and Research Committee the study was titled “A 12-month Randomised, Placebo-controlled Trial of Testosterone Replacement Therapy and Lifestyle Modification Versus Lifestyle Modification Alone on Visceral Adiposity and Markers of Cardiovascular Risk in Obese Middle-Aged and Ageing Men“.
As men age there is a small but progressive fall in serum testosterone levels, particularly in obese men. Increasingly, clinicians are consulted by ageing men with symptoms suggestive of testosterone deficiency. Symptoms include decreased sense of well-being, declining sexual performance, mood or memory changes. In these men a range of factors may be responsible, particularly obesity.
Testosterone replacement therapy (TRT) is increasingly used despite the lack of clear evidence for its benefits and safety.
Preliminary data suggests that TRT causes modest reductions in body fat, in particular abdominal fat, which may beneficially affect the development of cardiovascular disease through changes in several risk markers, such as cholesterol levels, insulin resistance and blood clotting factors.
It is suggested that those men who will benefit most from TRT are those who are obese and have lower testosterone levels but supportive evidence in this group is very limited. Importantly, obesity is associated with an increased risk of diabetes and cardiovascular disease.
We are using results from this study to determine whether TRT, in combination with a programme of lifestyle management, especially diet and exercise, offers an advantage over lifestyle management alone in obese ageing men.
During the trial 40 obese middle-aged and older men were treated with testosterone replacement therapy and monitored over a one year period to identify changes in abdominal body fats and risk factors for cardiovascular disease. Preliminary data analyses has shown that participants experienced a reduction of body fat and improved muscle mass as a result of the testosterone replacement with few other benefits. We are continuing to analyse this data.
The safety profile of TRT in terms of prostate disease and sleep apnoea (abnormal sleep patterns are associated with an increased risk of cardiovascular disease), the latter being more common in obesity, are being monitored.
A favourable benefit versus risk profile in this study may prompt subsequent larger interventional trials focusing on men with the increasingly common problems of obesity, predisposition to cardiovascular disease and diabetes, and who are increasingly presenting with low testosterone levels.
We are part of an Australian multi-centre double-blind, randomised, placebo-controlled trial to determine the efficacy of Testosterone treatment together with a lifestyle program to prevent progression to type 2 Diabetes Mellitus in men with pre-diabetes and low testosterone levels in comparison to a lifestyle program alone (T4DM).
The study is being supervised by the University of Adelaide with the other study sites being The Keogh Institute WA, Fremantle Hospital WA, The Austin Hospital Vic, and the Anzac Institute/Concord Hospital, NSW.
The study began enrolling subjects in late 2012 and will take five years to complete. 250 men will be recruited at the MIMR-PHI site.
– National Health and Medical Research Council (NHMRC)
– Bayer and Lilly
We have also been involved in developing a new transdermal formulation of testosterone that has entered clinical use in the USA and recently registered by the Australian TGA.
Weight Watchers Australia
Dept of Medical Imaging, Monash Health
Allan CA and McLachlan RI. Testosterone levels in the ageing male. Medicine Today (2012) (in press).
Sartorius G, Spasevska S, Idan A, Turner L, Forbes E, Zamojska A, Allan C, Ly L, Conway A, McLachlan R, Handelsman. Serum Testosterone, Dihydrotestosterone and Estradiol Concentrations in Older Men Self-Reporting Very Good Health: The Healthy Man Study. Journal of Clinical Endocrinology (Oxf) (2012) 1365-2265.2012.04432.x. [Epub ahead of print].
Allan CA, Strauss BJG, Forbes EA, Paul E, McLachlan RI. Variability in Total Testosterone Levels in Ageing Men with Symptoms of Androgen Deficiency. International Journal of Andrology (2011) 34(3):212-216.
Wang C, Ilani N, Arver S, McLachlan RI, Soulis T, Watkinson A. Efficacy and safety of the 2% formulation of testosterone topical solution applied to the axillae in androgen-deficient men. Journal of Clinical Endocrinology (Oxf)(2011) 75(6):836-43.
Allan CA, Strauss BJ, Forbes EA, Paul E, McLachlan RI. (2011) Variability in total testosterone levels in ageing men with symptoms of androgen deficiency. Int J Androl. 34(3): 212-216.
Allan CA, Peverill RE, Strauss BJ, Forbes EA, McLachlan RI. Waist-to-height ratio as a predictor of serum testosterone in ageing men with symptoms of androgen deficiency. Asian Journal of Andrology (2011) 13(3):424-31.
Sartorius G., Ly LP, Sikaris K, McLachlan R, Handelsman DJ. Predictive accuracy and sources of variability in calculated free testosterone estimates. Annals of Clinical Biochemistry (2009) 46 (2): 137-143.
Allan CA, Forbes EA, Strauss BJ, McLachlan RI. Testosterone therapy increases sexual desire in ageing men with low-normal testosterone levels and symptoms of androgen deficiency. International Journal of Impotence Research(2008) 20:396-401.
Allan CA, Strauss BJ, Burger HG, Forbes EA, McLachlan RI. Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in non-obese aging men. Journal of Clinical Endocrinology & Metabolism (2008) 93:139-146.
Allan CA, Strauss BJ, McLachlan RI. Body composition, metabolic syndrome and testosterone in ageing men.International Journal Impotence Research (2007) 19:448-457.
Allan CA, Strauss BJG, Burger HG, Forbes EA, McLachlan RI. The association between obesity and the diagnosis of androgen deficiency in symptomatic ageing men. Medical Journal of Australia (2006) 185:424-7.
McLachlan RI and Allan CA. Defining the prevalence and incidence of androgen deficiency in aging men: where are the goal posts? Journal of Clinical Endocrinology and Metabolism (2004) 89(12):5916-5919.
Allan CA and McLachlan RI. Age-Related Changes in Testosterone and the Role of Replacement Therapy in Older Men. Clinical Endocrinology (2004) 60(6):653-670.