New guideline offers recommendations for testosterone replacement therapy use

The Society's Clinical Practice Guideline on testosterone replacement therapy in men with hypogonadism offers recommendations on appropriate testing and prescribing practices. 

1.  The focus should be on having an accurate diagnosis from a clinician. 

• The diagnosis of hypogonadism requires ascertainment of men with symptoms of decreased testosterone, plus consistently low, accurately measured blood total and free testosterone in lab tests. The approach and definition of the diagnosis is the same for a man of any age. 

• Terms like "age-related," "late-onset," and "functional" hypogonadism are hard to define operationally and blur the line between treatable disease and normal aging. 

• There is insufficient evidence to support a general recommendation to perform population-level screening for hypogonadism in asymptomatic men with measurement of blood testosterone level. 

• Symptoms alone are not diagnostic of hypogonadism. Low energy, libido, and mood are common in aging men with many causes. Healthcare providers need to rule out reversible contributors first, such as obesity and medications such as corticosteroids or opioid use. 

• Healthcare providers must weigh the benefits of testosterone replacement therapy (TRT) against the risks. 

• Testosterone replacement therapy (TRT) at a dosage that is similar to what a man would typically make has clear benefits for men with appropriately diagnosed hypogonadism and a disease that affects the testes, pituitary, or hypothalamus as the cause. 

• For appropriately diagnosed hypogonadism due to being overweight or obese (BMI >27) and no other identified cause, weight loss is typically the first-line therapy 

2.  While recent studies have addressed some concerns, we need more research to fully understand TRT's risks. 

• The TRAVERSE trials (more than 5,200 men) found no meaningful increase in heart attack and stroke over a 1- to 4-year period. 

• But the TRAVERSE trials also showed roughly a 50% relative increase in pulmonary embolism and an increased incidence of bone fractures among testosterone-treated men. 

•  Long-term safety (including for prostate cancer) remains unestablished. 

• Screening and monitoring are needed if testosterone therapy is initiated. Prostate cancer develops slowly, and trials may not have followed men long enough, so risk assessment before starting treatment and careful monitoring during treatment remain essential. 

• The Society is calling for a long-term "Men's Health Initiative," analogous to the Women's Health Initiative, to close evidence gaps. 

3.  Consistent diagnosis and testing quality would ensure the men who need treatment receive it. 

• Testing is often inaccurate. Non-standardized assays mean the same blood sample can read "low" or "normal," depending on the lab and method. This drives both over- and under-diagnosis. 

• Hypogonadism diagnosis should be made by a healthcare provider based on at least two early-morning, fasting testosterone tests (common clinical threshold near 300 ng/dL). 

• Standardized testosterone assays are available and improve accurate diagnosis of hypogonadism and ensure men who need treatment receive it. 

• The use of a testosterone assay that has been certified by the CDC HoST program ensures that the assays have been standardized and "harmonized"; results from testosterone assays that are certified by the CDC are similar because harmonization is a process that smooths out the differences. This is very important because many testosterone assays are inaccurate, yield widely variable results, and have improper normal (reference) ranges.