January 13, 2020 11:58 am Chris Crawford – Physicians should prescribe testosterone for men with age-related low testosterone only to treat sexual dysfunction, the American College of Physicians said in a new, evidence-based clinical practice guideline published Jan. 7 in Annals of Internal Medicine.
"Physicians are often asked by patients about low 'T' and are skeptical about the benefits of testosterone treatment," said ACP President Robert McLean, M.D., in a news release. "The evidence shows that men with age-related low testosterone may experience slight improvements in sexual and erectile function."
The AAFP has endorsed the guideline, which contains four recommendations. The guideline does not address screening for or diagnosis of hypogonadism or monitoring of testosterone levels.
As men age, they experience a gradual decline in serum total testosterone, starting in their mid-30s, at an average rate of 1.6% per year.
About 20% of men older than 60, 30% older than 70 and 50% older than 80 experience low testosterone. However, the ACP noted that the prevalence of low testosterone with sexual dysfunction symptoms (defined as having at least three sexual symptoms, with total testosterone less than 320 nanograms per deciliter) is significantly lower.
It remains unknown whether nonspecific signs and symptoms associated with age-related low testosterone are a consequence of low testosterone levels or whether they result from other factors, such as chronic illness or medication use, the ACP said.
First, the ACP recommends that physicians discuss with patients whether to initiate testosterone treatment in men with age-related low testosterone accompanied by sexual dysfunction who want to improve sexual and erectile function, ensuring that the potential benefits, harms, costs and patient preferences are taken into account.
The guideline further suggests that physicians reevaluate symptoms within 12 months of initiation of treatment and periodically thereafter. Clinicians should discontinue treatment in these men if sexual function does not improve.
"Given that testosterone's effects were limited to small improvements in sexual and erectile function in men with low testosterone levels, it is unlikely that screening men for low testosterone levels or treating men without sexual or erectile dysfunction and low testosterone levels would be effective," McLean said in the release.
In a related recommendation statement, the ACP suggests that physicians consider intramuscular rather than transdermal formulations when starting testosterone treatment because the costs are considerably lower for the intramuscular formulation, and clinical effectiveness and harms of the two formulations are similar.
The annual cost per beneficiary for testosterone replacement therapy was $2,135.32 for the transdermal and $156.24 for the intramuscular formulation, according to 2016 Medicare Part D Drug Claims data, but this does not include costs associated with getting the IM injections.
"Most men are able to inject the intramuscular formulation at home and do not require a separate clinic or office visit for administration," McLean noted in the release.
Finally, the ACP advises that physicians not initiate testosterone treatment in men with age-related low testosterone to improve energy, vitality, physical function or cognition.
Evidence reviewed showed very little or no benefit of treatment for these common concerns of aging, the guideline stated.
All of the ACP guideline's recommendations are based on a systematic evidence review examining the efficacy and safety of testosterone treatment in adult men with age-related low testosterone that was conducted by the Minnesota Evidence-based Synthesis Center, a collaborative venture between the University of Minnesota and the Minneapolis Veterans Affairs Health Care System.
In formulating the recommendations, the ACP Clinical Guidelines Committee used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system to evaluate clinical outcomes described in the literature for sexual function, physical function, quality of life, energy/vitality, depression, cognition, serious adverse events, major adverse cardiovascular events and other adverse events.
AAFP Commission on Health of the Public and Science member James Stevermer, M.D., of Fulton, Mo., told AAFP News the Academy endorsed this guideline because it met the AAFP's rigorous standards for transparent, evidence-based clinical recommendations.
"It's based on a careful synthesis of randomized controlled trials of testosterone replacement lasting at least six months and that looked at patient-centered outcomes (sexual function, physician function, quality of life, mood, energy, cognition and fractures)," he said, adding that the meta-analysis was based on 38 randomized controlled trials, with 20 additional observational studies to help identify harms.
"The key point is that for most men with age-related low testosterone levels, testosterone replacement appears to have a small but significant benefit on sexual function," Stevermer continued. "The guideline suggests that clinicians discuss replacement therapy with these men, including potential harms, benefits, costs and preferences."
There's clearly an association with age, sex hormone levels and energy, quality of life, and other factors, Stevermer said, but he added that it remains challenging to untangle the underlying causes.
"Testosterone replacement improves many of these symptoms in men with inadequate testosterone because of specific disease or damage to the hypothalamus, pituitary or testes," he said. "It's not illogical to think that testosterone replacement might also help men with age-related low testosterone, but unfortunately, the benefit appears much more limited in this case."
Commenting on the ACP's recommendation that physicians reevaluate symptoms within 12 months and periodically thereafter and should discontinue treatment if sexual function does not improve, Stevermer said: "These specific recommendations were made based on the strength of the evidence. Improvement in sexual function with testosterone replacement was not seen in every man getting it, and it makes sense to reevaluate and stop a therapy that's not effective."
Mean age across the studies was 66 (partially because eight studies only enrolled men ages 65 and older), and relatively few men younger than 50 were included in the evidence review, he noted, but with testosterone levels starting to decline as men reach their mid-30s, physicians are likely to get questions on the topic from men of all ages.
"The discussion is often initiated by patients wondering if testosterone replacement will improve symptoms they are concerned about, so it's typically a case-by-case decision," Stevermer said.
Finally, Stevermer said the meta-analysis found no significant harms with testosterone replacement for these men.
"However, the data are limited," he acknowledged, "and uncommon harms may well have been missed in the studies reviewed."