Late-onset hypogonadism in men over 40 - how to use the updated EAU 2025 guidelines and new findings on the cardiovascular safety of testosterone therapy.

Late-onset hypogonadism affects roughly two to eight percent of European men aged 40-79 years.

• Prevalence is approximately 2-8% in European men aged 40-79 years.
• Prevalence increases with advancing age, obesity, and cardiometabolic comorbidities.
• The condition is defined by androgen-deficiency symptoms and persistently low testosterone.

The 2025 EAU guidelines establish a unified biochemical threshold of total testosterone below 12 nmol/L for diagnosing late-onset hypogonadism.

• Diagnosis requires confirmation by two morning samples with total testosterone below 12 nmol/L.
• The guidelines emphasise baseline assessment of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) before therapy.
• Baseline blood pressure and haematocrit assessment are also required before initiating therapy.
• This represents an update from the European Association of Urology (EAU) 2025 guidelines.

The TRAVERSE trial showed that transdermal testosterone replacement does not increase major adverse cardiovascular events.

• TRAVERSE was a large multicentre trial.
• The trial used transdermal testosterone replacement therapy.
• Despite no increase in major adverse cardiovascular events, a mild rise in systolic blood pressure was observed.
• The finding of elevated systolic blood pressure was reflected in the latest US FDA labelling changes for testosterone products.

The authors propose a four-step clinical algorithm for managing late-onset hypogonadism.

• The algorithm encompasses precise diagnosis as the first step.
• The second step involves judicious initiation of treatment.
• The third step involves integrated management of cardiometabolic risk factors.
• The fourth step involves personalised fertility preservation.
• The approach is intended to permit effective and safe management of symptomatic late-onset hypogonadism while mitigating long-term risks.