After the age of 30, most men begin to experience a gradual decline in their levels of testosterone. Helping to address how physicians should advise and treat these men is a new 2020 evidence-based clinical guideline by the American College of Physicians (ACP). It was developed by a systematic review of the efficacy and safety of testosterone treatment in adult men with age-related low testosterone. The resulting clinical outcomes were evaluated by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and included sexual function, physical function, quality of life, energy and vitality, depression, cognition, serious adverse events, major adverse cardiovascular events, and other adverse events.

There were 39 randomized controlled trials that met the inclusion criteria to evaluate testosterone therapy. The mean age of participants was 66 years, and follow-up with each entrant was conducted between 6 and 36 subsequent months. The mean baseline total testosterone level among the participants was 10.4nmol/L (300ng/dL) or lower.

The resulting recommendations for physicians included advisement to discuss whether to initiate testosterone treatment in men with age-related low testosterone with sexual dysfunction who want to improve sexual and erectile function based on the potential benefits, harms, costs, and patient preferences. At this time, it is uncertain whether nonspecific signs and symptoms associated with age-related low testosterone are a consequence of age-related low testosterone levels or a result of other factors, such as chronic illnesses or medications; therefore the guideline advises not to initiate treatment in men with age-related low testosterone if the health goals are to improve energy, vitality, physical function, or cognition. The FDA requires the pharmaceutical industry to label all testosterone medications to clearly state that their products are approved for use only in persons with low testosterone levels due to known causes.

The ACP recommends that physicians reevaluate patient symptoms within 12 months and periodically after that. Safety monitoring varied across trials, so specific evidence-based monitoring recommendations are not outlined, but there is still advisement to provide regular monitoring due to possible elevation of risk for prostate cancer risk and polycythemia. The guideline addresses neither screening or diagnosis of hypogonadism nor monitoring of testosterone levels. The results from trials that included only obese men or men with diabetes or metabolic syndrome were similar to those of the overall pooled analysis.

Due to differences in sexual function outcomes based on baseline testosterone level, the testosterone level in adult males at which to start treatment remains unclear. Treating physicians are encouraged to consider intramuscular therapy over transdermal formulations (patches, creams, pellets) since the cost is lower, while effectiveness/harms are similar to those of the other forms. If sexual function in the patient does not improve, treatment should be discontinued. Because studies have had limited follow-up, the evidence on long-term effects of testosterone treatment is lacking. Conclusive evidence regarding mortality also is deficient because of imprecision, low event rates, and potential fragility of the results.

It was found that studies with different baseline levels or different testosterone medication formulations did not result in significant variations in outcomes. Physician takeaways from the guideline include talking points for patients, and should cover that testosterone may improve sexual function but response varies; awareness that if sexual symptoms do not improve, treatment should be stopped; that testosterone does not improve other common concerns of aging; and that both injectable and topical forms can improve sexual function, but injectable forms can be much more affordable.