New guidelines for testosterone treatment in adult men with age-related low testosterone

Testosterone normally decreases with age in men beginning in their mid-30s, with a rate of decline averaging approximately 1.6% per year. Using a cutoff of a total testosterone less than 325 ng/dL, the incidence of low testosterone is approximately 20% after age 60 years, and 30% after age 70. While the change in labs values has been reasonably validated, there is some uncertainty about whether many of the symptoms that are sometimes attributed to testosterone deficiency, including fatigue and decreased muscle mass, are actually caused by low testosterone.

Dr. Gerald Hansen and Dr. Neil Skolnik

Additional potential symptoms of testosterone deficiency include changes in bone mineral density, decreased libido, depression, erectile dysfunction, loss of hair, and general weakness. Since the symptoms are nonspecific, it is often unclear if someone should be tested or treated for testosterone deficiency. To address this issue, the American College of Physicians commissioned a systematic review of the evidence on testosterone-replacement therapy for age-related testosterone deficiency.¹

The evidence review of testosterone replacement in men with age-related low testosterone found the following.

• Low-certainty evidence of improvement in quality of life
• Moderate-certainty evidence of a small improvement in sexual function
• Low-certainty evidence of a small improvement in erectile function
• Low-certainty evidence showing little to no improvement in physical function
• Low-certainty evidence of a small increase to no difference in adverse cardiovascular events
• Moderate-certainty evidence of no increase in the risk for serious adverse events

The trials were not powered to assess mortality, but pool analysis showed fewer deaths among patients treated with testosterone than those who received placebo (odds ratio, 0.47; 95% confidence interval, 0.25-0.89). There were no differences in cognitive function, and the improvement in vitality and fatigue was “less than a small amount.” Evidence from an observational trial showed no increased risk for mortality, cardiovascular events, prostate cancer, or pulmonary embolus or deep vein thrombosis. Of note, most studies excluded men with recent cardiovascular disease.

This evidence review led to the following recommendations.²

Recommendation 1a

Clinicians should have a discussion regarding the potential risk and benefits of treatment with the patients who have documented age-related low testosterone (testosterone levels less than 10.4 nmol/L or 300 ng/dL) and are suffering from sexual dysfunction or have a desire to enhance their sexual function.

This recommendation was based on evidence showing small improvement in sexual function and erectile dysfunction.

Recommendation 1b

For patients who opt for treatment based on recommendation 1a, clinicians should reevaluate the benefit of treatment within 12 months. If a patient is not receiving any benefit in sexual function by 12 months, it is recommended that treatment be stopped at that time.

The ACP recommendation to stop treatment if a patient lacks improvement of sexual function within 12 months stems from low or insufficient evidence regarding potential harm of treatment. If the treatment is not helping the target symptom then the benefit no longer outweighs the potential harm.