Testosterone therapy in older men: clinical implications of recent landmark trials.

Testosterone therapy produced modest but clinically significant benefits on self-reported energy, mood, sexual function, and satisfaction in older men without identifiable HPT axis pathology.

• Trials were placebo-controlled and assessed testosterone therapy for durations of up to 3 years
• Target population was middle-aged and older men with symptoms and possible signs of hypogonadism or end-organ androgen deficiency
• Men had low or low-normal serum testosterone concentrations but no identifiable hypothalamic-pituitary-testicular axis pathology
• Benefits were described as 'modest-but clinically significant' on average self-reported outcomes

Testosterone therapy in conjunction with a lifestyle programme reversed or reduced incident type 2 diabetes in men at high risk of or newly diagnosed with type 2 diabetes.

• The effect was observed specifically when testosterone was used in conjunction with a lifestyle programme
• The benefit applied to men at high risk of type 2 diabetes as well as those newly diagnosed with type 2 diabetes
• This was identified as one of the landmark trial findings within the ≤3 year treatment period

Testosterone therapy modestly improved objectively assessed muscle strength and timed walking distance.

• Improvements in physical function were assessed using objective measures including timed walking distance
• Muscle strength improvements were also objectively assessed
• The improvements were characterized as 'modest' in magnitude

Testosterone therapy increased bone density and strength but did not reduce falls or typical osteoporotic fractures, and unexpectedly increased the risk of fractures typically attributable to trauma.

• Bone density and bone strength both increased with testosterone therapy
• Despite improvements in bone density and strength, falls were not reduced
• Typical osteoporotic fractures were not reduced
• The paper describes the increased risk of trauma-attributable fractures as 'surprising'
• Treatment duration was up to 3 years

Testosterone therapy did not significantly increase the risk of myocardial infarction, stroke, or prostate cancer.

• Cardiovascular outcomes assessed included myocardial infarction and stroke
• Prostate cancer incidence was also assessed as a safety endpoint
• No statistically significant increase was found for any of these outcomes over the trial duration of ≤3 years
• These findings help address longstanding safety concerns about testosterone therapy in older men

Testosterone therapy for men with hypogonadism due to identifiable hypothalamic-pituitary-testicular pathology is considered uncontroversial, whereas its use for men without such pathology has been uncertain.

• The paper distinguishes between classical hypogonadism with identifiable HPT axis pathology and functional/age-related hypogonadism without such pathology
• The risks and benefits for men without HPT pathology were described as 'uncertain' prior to these landmark trials
• The landmark trials specifically targeted men with symptoms and low/low-normal testosterone but no HPT pathology