ACP Issues Guidelines for Use of Testosterone Therapy in Age-Related Low Testosterone

To clarify the potential benefits and harms of testosterone therapy in men with age-related low testosterone levels, the American College of Physicians (ACP) has issued a set of recommendations, published in the Annals of Internal Medicine.¹ The guidelines are based on a review of evidence from 38 randomized controlled trials that evaluated the effects of testosterone therapy on various outcome measures, including quality of life, sexual and physical function, and adverse events among older men with low testosterone levels.²

Key Recommendations and Supporting Evidence

Clinicians should discuss potential benefits, harms, costs, and patient preferences when having conversations with men about initiating testosterone treatment for age-related low testosterone.¹

•  Evidence suggests that testosterone therapy may provide small improvements in sexual functioning in this population, but does not support any benefit for other common concerns of aging, including changes in physical function, depressive symptoms, energy or vitality, or cognition.^1,2
• With regard to potential harms, evidence was judged to be insufficient for most outcomes, including serious adverse events, cardiac-specific adverse events, prostate cancer, and mortality.^1,2

Clinicians should reevaluate symptoms within 12 months of starting testosterone therapy, and periodically thereafter. Treatment should be discontinued in men who do not show any improvement in sexual function.¹

• The majority of existing evidence does not examine treatment for >12 months; thus, the long-term benefits and harms of testosterone therapy are not well understood.¹

When initiating testosterone treatment, intramuscular testosterone formulations are preferred to transdermal because costs are substantially lower despite similar effectiveness.¹

• Clinical effectiveness, benefits, and harms were found to be similar between the 2 formulations in the ACP’s evidence review, although no clinical trials directly compared them.²
• Costs of injectable testosterone are more than 10 times lower than those of transdermal formulations.¹
•  The oral formulation of testosterone undecanoate is contraindicated in men with hypogonadal conditions, including age-related hypogonadism.²

Testosterone therapy should not be initiated in men with age-related low testosterone to improve vitality or energy, physical function, or cognition.

• There is a dearth of evidence to support the use of testosterone therapy for these indications; therefore, the ACP only recommends prescribing testosterone therapy in men with age-related low testosterone to treat sexual dysfunction.^1,2

Caution should be used when applying these recommendations to patients with comorbid conditions.¹ In addition, evidence did not show clear differences in outcomes for sexual function among men with varying baseline testosterone levels, and therefore there is no specific recommendation for a level at which to initiate treatment.¹

In an accompanying editorial, E. Victor Adlin, MD, from the Lewis Katz School of Medicine at Temple University in Philadelphia, Pennsylvania, clarified the significance of these ACP guidelines³: “Direct-to-consumer advertising has familiarized the concept of low testosterone as a cause of symptoms in aging men, and the use of testosterone therapy in older men has increased considerably in recent years, often in men in whom low testosterone levels have not been demonstrated.”

He added, “This and other current guidelines agree that the recent increase in use of testosterone treatment for nonspecific symptoms of aging, especially in men without confirmed testosterone deficiency, is not indicated…. The decision to initiate testosterone therapy for age-related low testosterone should depend on a discussion between the patient and a well-informed caregiver, with full consideration of the patient’s values and wishes.”³

Disclosure: One author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

References

1. Qaseem A, Horwitch CA, Vijan S, Etxeandia-Ikobaltzeta I, Kansagara D; for the Clinical Guidelines Committee of the American College of Physicians. Testosterone treatment in adult men with age-related low testosterone: a clinical guideline from the American College of Physicians [published online January 6, 2020]. Ann Intern Med. doi:10.7326/M19-0882

2. Diem SJ, Greer NL, MacDonald R, et al. Efficacy and safety of testosterone treatment in men: an evidence report for a clinical practice guideline by the American College of Physicians [published online January 6, 2020]. Ann Intern Med. doi:10.7326/M19-0830

3. Adlin EV. Age-related low testosterone [published online January 6, 2020]. Ann Intern Med. doi:10.7326/M19-3815