Effective testosterone therapy in men with pathological hypogonadism should target the leading symptom of deficiency, but should be used with caution in those with cardiovascular disease, new guidelines from the Endocrine Society of Australia recommend.
The guidelines on treatment are consistent with those just released on diagnosis and indications for therapy. They stress that pathological hypogonadism should be regarded as a clinical diagnosis to be confirmed by hormone assays, rather than the other way around.
Writing in the Medical Journal of Australia, Professor Bu Yeap from the University of Western Australia and colleagues said testosterone is the native hormone that should be replaced.
“In many ways, testosterone is ‘three hormones in one’ – an important physiological consideration when using testosterone rather than other androgens for replacement therapy,” they said. Testosterone supplementation provides a substrate for the usual pathways of metabolism to 5-alpha-dihydrotestosterone and oestradiol.
“Convenient and cost-effective treatment modalities include depot intramuscular injection and transdermal administration (gel, cream or liquid formulations),” they said. The choice can be personalised.
Treatment should be monitored for efficacy and safety, focusing on ameliorating symptoms, restoring virilisation, avoiding polycythaemia and maintaining or improving bone mineral density.
“Treatment aims to relieve an individual’s symptoms and signs of androgen deficiency by administering standard doses and maintaining circulating testosterone levels within the reference interval for eugonadal men,” they said.
Current evidence on links between testosterone treatment and cardiovascular outcomes is contradictory and inconclusive. There have been no adequately-powered randomised controlled trials with cardiovascular events as a pre-specified outcome.
“Additional studies are needed to clarify whether testosterone therapy influences cardiovascular risk,” the guidelines state.
“A cautious approach to testosterone replacement is warranted in older, frail men, particularly in those with a history of cardiovascular disease. In complex cases, evaluation by an endocrinologist is recommended.”
In general, evaluation for cardiovascular disease and prostate cancer risks should be undertaken as appropriate for eugonadal men of a similar age.
Although there is no evidence that appropriate use of testosterone therapy increases the risk of prostate cancer, if there is a “reasonable possibility” of substantive pre-existing prostate disease then digital rectal examination and PSA testing is recommended.
The guidelines list a number of key questions that need to be researched in well-controlled clinical trials. They include the role of testosterone therapy in older men without pathological hypogonadism, the effect of treatment on weight loss and progression to type 2 diabetes, and whether it might be beneficial in men with prolonged suppression of the HPT axis resulting from recreational misuse of androgens.